Chronic liver disease is one of the most common causes of premature death in Americans. My career goal is to improve the outcome of individuals with chronic liver disease by identifying the optimal means for diagnosis, monitoring, treatment and prevention. The path I have chosen to achieve this goal is through engagement in clinical epidemiology and patient-oriented, effectiveness research.

Since the development of the MELD score which recognizes the importance of renal function in the prognosis of patients with end stage liver disease, one of the areas that we have had intense interest has been acute and chronic renal injury in patients undergoing liver transplantation. Liver transplantation represents a unique opportunity for research, because of the potential for reversal of the renal injury as well as access to biological materials.

Clinical Focus

  • Gastroenterology
  • Hepatitis C
  • Hepatology
  • Hepatitis B, Chronic
  • Liver Transplantation
  • Liver Cirrhosis

Academic Appointments

Administrative Appointments

  • Chief, Division of Gastroenterology & Hepatology, Department of Medicine, Stanford Unversity (2013 - Present)

Boards, Advisory Committees, Professional Organizations

  • Treasurer, AASLD (2014 - 2017)
  • Chair, Development Committee, AASLD (2011 - 2014)
  • Senior Fellow, Center for Innovation in Global Health (2015 - Present)
  • Chair, Clinical Research Committee, AASLD (2008 - 2011)
  • Associate Editor, Hepatology (2008 - 2011)
  • Member, American Gastroenterological Association (1994 - Present)
  • Member, AASLD (1994 - Present)
  • Member, American College of Gastroenterology (1994 - Present)
  • Member, International Liver Transplant Society (1998 - Present)
  • Member, American Society for Transplant Physicians (1998 - Present)

Professional Education

  • Fellowship:Mayo Graduate School of Medicine (1998) MN
  • Fellowship:Mayo Graduate School of Medicine (1997) MN
  • Residency:University of Arkansas for Medical Sciences Medical Center (1994) AR
  • Professional Education:University of Pennsylvania (1992) PA
  • Residency:Seoul National University Hospital (1990)
  • Internship:Seoul National University Hospital (1987)
  • Medical Education:Seoul National University (1986)
  • Board Certification: Transplant Hepatology, American Board of Internal Medicine (2008)
  • Board Certification: Gastroenterology, American Board of Internal Medicine (1998)
  • M.B.A., Wharton School, University of Pennsylvania, Health Care Administration (1992)
  • M.Sc., Seoul National University, Clinical Research (1990)
  • M.D., Seoul National University, Medicine (1986)


Graduate and Fellowship Programs

  • Gastroenterology & Hepatology (Fellowship Program)


All Publications

  • Beneficial and harmful effects of nonselective beta blockade on acute kidney injury in liver transplant candidates. Liver transplantation Kim, S. G., Larson, J. J., Lee, J. S., Therneau, T. M., Kim, W. R. 2017; 23 (6): 733-740


    Nonselective beta-blockers (NSBBs) have played an important role in the prevention of portal hypertensive bleeding in patients with cirrhosis. However, recent studies have suggested that NSBBs may be harmful in some patients with end-stage liver disease. The purpose of this article is to evaluate the association between use of NSBB and the incidence of acute kidney injury (AKI). We conducted a nested case-control study in a cohort of liver transplant wait-list registrants. Each patient with AKI was matched to a control by the Model for End-Stage Liver Disease-Na score, age, serum creatinine, and follow-up duration. Out of a total of 2361 wait-list registrants, 205 patients developed AKI after a median follow-up duration of 18.2 months. When compared with matched controls, ascites (79.0% versus 51.7%) and non-Caucasian race (16.6% versus 7.8%) were more common among the cases. The frequency of NSBB use was higher among the cases than controls, albeit insignificantly (45.9% versus 37.1%; P = 0.08). In multivariate analyses, the impact of nonselective beta blockade on the development of AKI was dependent on the presence of ascites: nonselective beta blockade in patients with ascites significantly increased the risk of AKI (hazard ratio [HR], 3.31; 95% confidence interval [CI], 1.57-6.95), whereas in patients without ascites, NSBB use reduced it (HR, 0.19; 95% CI, 0.06-0.60). Potential benefits and harms of a NSBB in terms of AKI depend on the presence of ascites in liver transplant candidates. NSBB therapy in patients with cirrhosis may need to be individualized. Liver Transplantation 23 733-740 2017 AASLD.

    View details for DOI 10.1002/lt.24744

    View details for PubMedID 28187503

    View details for PubMedCentralID PMC5449204

  • Utility in Treating Kidney Failure in End-Stage Liver Disease With Simultaneous Liver-Kidney Transplantation TRANSPLANTATION Cheng, X. S., Stedman, M. R., Chertow, G. M., Kim, W. R., Tan, J. C. 2017; 101 (5): 1111-1119


    Simultaneous liver-kidney (SLK) transplantation plays an important role in treating kidney failure in patients with end-stage liver disease. It used 5% of deceased donor kidney transplanted in 2015. We evaluated the utility, defined as posttransplant kidney allograft lifespan, of this practice.Using data from the Scientific Registry of Transplant Recipients, we compared outcomes for all SLK transplants between January 1, 1995, and December 3, 2014, to their donor-matched kidney used in kidney-alone (Ki) or simultaneous pancreas kidney (SPK) transplants. Primary outcome was kidney allograft lifespan, defined as the time free from death or allograft failure. Secondary outcomes included death and death-censored allograft failure. We adjusted all analyses for donor, transplant, and recipient factors.The adjusted 10-year mean kidney allograft lifespan was higher in Ki/SPK compared with SLK transplants by 0.99 years in the Model for End-stage Liver Disease era and 1.71 years in the pre-Model for End-stage Liver Disease era. Death was higher in SLK recipients relative to Ki/SPK recipients: 10-year cumulative incidences 0.36 (95% confident interval 0.33-0.38) versus 0.19 (95% confident interval 0.17-0.21).SLK transplantation exemplifies the trade-off between the principles of utility and medical urgency. With each SLK transplantation, about 1 year of allograft lifespan is traded so that sicker patients, that is, SLK transplant recipients, are afforded access to the organ. These data provide a basis against which benefits derived from urgency-based allocation can be measured.

    View details for DOI 10.1097/TP.0000000000001491

    View details for Web of Science ID 000400762500040

    View details for PubMedID 28437790

  • Reduction in Liver Transplant Wait-Listing in the Era of Direct-Acting Antiviral Therapy HEPATOLOGY Flemming, J. A., Kim, W. R., Brosgart, C. L., Terrault, N. A. 2017; 65 (3): 804-812


    Direct-acting antiviral (DAA) therapy, recently approved for patients with decompensated cirrhosis (DC) secondary to hepatitis C virus (HCV), is associated with improved hepatic function. We analyzed trends in liver transplant (LT) wait-listing (WL) to explore potential impact of effective medical therapy on WL registration. This is a cohort study using the Scientific Registry of Transplant Recipients database from 2003 to 2015. A total of 47,591 adults wait-listed for LT from HCV, hepatitis B virus (HBV), and nonalcoholic steatohepatitis (NASH) were identified. LT indication was defined as DC if the Model for End-Stage Liver Disease (MELD) at WL was ≥15 or hepatocellular carcinoma (HCC). Era of listing was divided into interferon (IFN; 2003-2010), protease inhibitor (PI; 2011-2013), and direct-acting antiviral (DAA; 2014-2015). Annual standardized incidence rates of WL were analyzed using Poisson regression. Adjusted incidences of LT WL for DC in HCV patients decreased by 5% in the PI era (P = 0.004) and 32% in the DAA era (P < 0.001) compared to the IFN era. Listing for DC in HBV also decreased in the PI (-17%; P = 0.002) and DAA eras (-24%; P < 0.001). Conversely, WL for DC in NASH increased by 41% in the PI era (P < 0.001) and 81% in the DAA era (P < 0.001). WL for HCC in both the HCV and NASH populations increased in both the PI and DAA eras (P < 0.001 for all) whereas HCC WL in HBV remained stable (P > 0.05 for all).The rate of LT WL for HCV complicated by DC has decreased by over 30% in the era of DAA therapy. Further reductions in WL are anticipated with increased testing, linkage to care, and access to DAA therapy. (Hepatology 2017;65:804-812).

    View details for DOI 10.1002/hep.28923

    View details for Web of Science ID 000397301300007

    View details for PubMedID 28012259

  • Management of Renal Failure in End-Stage Liver Disease: A Critical Appraisal LIVER TRANSPLANTATION Cheng, X. S., Tan, J. C., Kim, W. R. 2016; 22 (12): 1710-1719


    Renal failure is a late consequence of end-stage liver disease (ESLD). Even with liver transplantation, pretransplant renal impairment remains a strong predictor of posttransplant mortality. This review seeks to summarize and critically appraise common therapies used in this setting, including pharmacologic agents, procedures (transjugular intrahepatic portosystemic shunt, renal replacement therapy), and simultaneous liver-kidney transplantation. More experimental extracorporal modalities, eg, albumin dialysis or bioartificial livers, will not be discussed. A brief discussion on the definition and pathophysiologic underpinnings of renal failure in ESLD will be held at the beginning to lay the groundwork for the main section. Liver Transplantation 22 1710-1719 2016 AASLD.

    View details for DOI 10.1002/lt.24609

    View details for Web of Science ID 000389079500011

    View details for PubMedID 27875032

  • Diabetes Mellitus Heightens the Risk of Hepatocellular Carcinoma Except in Patients With Hepatitis C Cirrhosis AMERICAN JOURNAL OF GASTROENTEROLOGY Yang, J. D., Mohamed, H. A., Cvinar, J. L., Gores, G. J., Roberts, L. R., Kim, W. R. 2016; 111 (11): 1572-1580
  • Time trends in the health care burden and mortality of acute on chronic liver failure in the United States. Hepatology Allen, A. M., Kim, W. R., Moriarty, J. P., Shah, N. D., Larson, J. J., Kamath, P. S. 2016


    Acute on chronic liver failure (ACLF) is associated with multisystem organ failure and poor prognosis in hospitalized patients with cirrhosis. We aimed to determine time trends in the epidemiology, economic burden, and mortality of ACLF in the United States. The National Inpatient Sample database was queried between 2001 and 2011. ACLF was defined as two or more extrahepatic organ failures in patients with cirrhosis. The primary outcomes were trends in hospitalizations, hospital costs, and inpatient mortality. The number of hospitalizations for cirrhosis in the United States nearly doubled from 371,000 in 2001 to 659,000 in 2011. The prevalence of ACLF among those hospitalizations increased from 1.5% (n = 5,400) to 5% (n = 32,300). The inpatient costs increased 2-fold for cirrhosis ($4.8 billion to $9.8 billion) and 5-fold ($320 million to $1.7 billion) for ACLF. In 2011, the cost per hospitalization for ACLF was 3.5-fold higher than that for cirrhosis ($53,570 versus $15,193). The in-hospital fatality rates decreased from 65% to 50% for ACLF and from 10% to 7% for cirrhosis. The organ failure trends in ACLF showed an increasing proportion of cardiovascular and cerebral and decreasing proportion of respiratory and renal failure. Age, male sex, and the number and types of organ failure were predictors of death in ACLF.Cirrhosis and ACLF represent a substantial and increasing health and economic burden in the United States; these data highlight an urgent need for research on pathophysiological mechanisms and effective therapy as well as for education of health care providers of its importance in the care of patients with cirrhosis. (Hepatology 2016;64:2165-2172).

    View details for DOI 10.1002/hep.28812

    View details for PubMedID 27696493

  • Predicting Outcomes on the Liver Transplant Waiting List in the United States: Accounting for Large Regional Variation in Organ Availability and Priority Allocation Points. Transplantation Hart, A., Schladt, D. P., Zeglin, J., Pyke, J., Kim, W. R., Lake, J. R., Roberts, J. P., Hirose, R., Mulligan, D. C., Kasiske, B. L., Snyder, J. J., Israni, A. K. 2016; 100 (10): 2153-2159


    The probability of liver transplant and death on the waiting list in the United States varies greatly by donation service area (DSA) due to geographic differences in availability of organs and allocation of priority points, making it difficult for providers to predict likely outcomes after listing. We aimed to develop an online calculator to report outcomes by region and patient characteristics.Using the Scientific Registry of Transplant Recipients database, we included all prevalent US adults aged 18 years or older waitlisted for liver transplant, examined on 24 days at least 30 days apart over a 2-year period. Outcomes were determined at intervals of 30 to 365 days. Outcomes are reported by transplant program, DSA, region, and the nation for comparison, and can be shown by allocation or by laboratory model for end-stage liver disease (MELD) score (6-14, 15-24, 25-29, 30-34, 35-40), age, and blood type.Outcomes varied greatly by DSA; for candidates with allocation MELD 25-29, the 25th and 75th percentiles of liver transplant probability were 30% and 67%, respectively, at 90 days. Corresponding percentiles for death or becoming too sick to undergo transplant were 5% and 9%. Outcomes also varied greatly for candidates with and without MELD exception points.The waitlist outcome calculator highlights ongoing disparities in access to liver transplant and may assist providers in understanding and counseling their patients about likely outcomes on the waiting list.

    View details for DOI 10.1097/TP.0000000000001384

    View details for PubMedID 27490411

  • Protecting the Kidney in Liver Transplant Candidates: Practice-Based Recommendations From the American Society of Transplantation Liver and Intestine Community of Practice AMERICAN JOURNAL OF TRANSPLANTATION O'Leary, J. G., Levitsky, J., Wong, F., Nadim, M. K., Charlton, M., Kim, W. R. 2016; 16 (9): 2516-2531


    Acute kidney injury (AKI) and chronic kidney disease (CKD) are common in patients awaiting liver transplantation, and both have a marked impact on the perioperative and long-term morbidity and mortality of liver transplant recipients. Consequently, we reviewed the epidemiology of AKI and CKD in patients with end-stage liver disease, highlighted strategies to prevent and manage AKI, evaluated the changing liver transplant waiting list's impact on kidney function, delineated important considerations in simultaneous liver-kidney transplant selection, and projected possible future transplant policy changes and outcomes. This review was assembled by experts in the field and endorsed by the American Society of Transplantation Liver and Intestinal Community of Practice and Board of Directors and provides practice-based recommendations for preservation of kidney function in patients with end-stage liver disease.

    View details for DOI 10.1111/ajt.13790

    View details for Web of Science ID 000383774700007

    View details for PubMedID 26990924

  • Lower Observed Hepatocellular Carcinoma Incidence in Chronic Hepatitis B Patients Treated With Entecavir: Results of the ENUMERATE Study AMERICAN JOURNAL OF GASTROENTEROLOGY Ahn, J., Lim, J. K., Lee, H. M., Lok, A. S., Mindie Nguyen, M., Pan, C. Q., Mannalithara, A., Te, H., Reddy, K. R., Huy Trinh, H., Chu, D., Tram Tran, T., Lau, D., Leduc, T., Min, A., Loc Trong Le, L. T., Bae, H., Sang Van Tran, S. V., Do, S., Hann, H. L., Wong, C., Han, S., Pillai, A., Park, J. S., Tong, M., Scaglione, S., Woog, J., Kim, W. R. 2016; 111 (9): 1297-1304
  • Nonobese Fatty Liver Disease. Clinical gastroenterology and hepatology Kim, D., Kim, W. R. 2016


    Nonalcoholic fatty liver disease (NAFLD) refers to a group of conditions characterized by hepatic steatosis in the absence of significant alcohol consumption. NAFLD is seen commonly in patients with metabolic abnormalities associated with obesity, such as type II diabetes, dyslipidemia, and metabolic syndrome. Evidently, however, not all obese subjects develop NAFLD and, more importantly, NAFLD can be found in nonobese individuals. Although NAFLD occurring in nonobese subjects has been reported in children and adults of all ethnicities, it appears to be recognized more frequently in Asians, even when strict ethnicity-specific body mass index criteria are used to define obesity. Studies based on liver biopsies suggest that the prevalence of nonalcoholic steatohepatitis and fibrosis does not differ significantly between nonobese NAFLD and NAFLD in obese patients. Visceral obesity as opposed to general obesity, high fructose and cholesterol intake, and genetic risk factors (eg, palatin-like phospholipase domain-containing 3) may be associated with nonobese NAFLD. In general, nonalcoholic steatohepatitis is associated with increased mortality, primarily from cardiovascular causes, independent of other metabolic factors. Although data regarding the mortality impact of nonobese NAFLD are not as mature, it may be important to identify high-risk nonobese NAFLD patients and manage their metabolic profile. Currently, lifestyle modification to reduce visceral adiposity, including dietary changes and physical activity, remains the standard of care in patients with nonobese NAFLD.

    View details for DOI 10.1016/j.cgh.2016.08.028

    View details for PubMedID 27581063

  • Potential Efficacy of Pegylated Interferon-alpha and a Nucleos(t)ide Analogue as Combination Therapy for HBeAg-Positive Chronic Hepatitis B GUT AND LIVER Wi, C., Kim, W. R., Gross, J. B., Stadheim, L. M., Poterucha, J. J. 2016; 10 (4): 611-616


    Despite the potent suppression of the hepatitis B virus with modern antiviral agents, only a minority of HBeAg-positive patients achieve hepatitis B e antigen seroconversion. We aimed to explore the potential efficacy of combination therapy consisting of pegylated interferon (p-IFN) and an oral antiviral agent in patients with HBeAgpositive chronic hepatitis B.The treatment protocol consisted of p-IFN-α-2a at 180 μg/wk for 48 weeks, with either entecavir or tenofovir added 8 weeks after the initiation of p-IFN and continued for at least 6 months after HBe seroconversion was achieved.To date, 10 patients have been treated under the protocol (eight adults, mean age 36±8 years; two adolescents, aged 12 and 16 years). All eight adult patients experienced loss of HBeAg at a mean of 72.3±66.9 weeks, including six patients who also developed anti-HBe and one patient who had HBs seroconversion. Although both adolescents remain on therapy, one adolescent had HBs seroconversion without HBe seroconversion. A total of nine of our 10 patients experienced a favorable serological transition.The combination of p-IFN and a modern oral antiviral agent may be more effective than monotherapy with either class of agent in the treatment of HBeAg-positive chronic hepatitis B patients.

    View details for DOI 10.5009/gnl14256

    View details for Web of Science ID 000379989900023

    View details for PubMedID 26190580

    View details for PubMedCentralID PMC4933423

  • Increasing prevalence of cirrhosis among U.S. adults aware or unaware of their chronic hepatitis C virus infection. Journal of hepatology Udompap, P., Mannalithara, A., Heo, N., Kim, D., Kim, W. R. 2016; 64 (5): 1027-1032


    Cirrhosis from hepatitis C virus (HCV) infection is a major cause of end-stage liver disease and hepatocellular carcinoma worldwide. We determine the prevalence of cirrhosis among HCV-infected American adults including those unaware of their infection.Using the National Health and Nutrition Examination Survey (NHANES) data, we identified participants aged⩾20 years with detectable serum HCV RNA. The prevalence of advanced fibrosis and cirrhosis was determined for Eras 1 (1988-94), 2 (1999-2006) and 3 (2007-12) by using FIB-4 > 3.25 and APRI > 2.0, respectively.Out of 52,644 NHANES examinees, 49,429 were tested for HCV, of whom 725 met the inclusion criteria (positive HCV RNA with available data for FIB-4 and APRI). Based on APRI, 6.6% (95% confidence interval [CI]:2.2-11.0) of HCV-infected adults in Era 1, 7.6% (95%CI:3.4-11.8) in Era 2 and 17.0% (95%CI:8.0-26.0) in Era 3 had cirrhosis. In the multivariable regression analysis, this era effect was attributable to increasing age (odds ratio [OR]:1.04, 95%CI:1.02-1.07), diabetes (OR:2.33, 95%CI:1.01-5.40) and obesity (OR:2.96, 95%CI:1.15-7.57). Cirrhosis was as common among respondents who were unaware of their infection as those who were aware (both 11%). Results were identical when FIB-4 was used.Among HCV-infected American adults, the proportion with cirrhosis has increased rapidly. Cirrhosis prevalence remains high in individuals unaware of their HCV infection. These data highlight the urgency for HCV screening regardless of symptoms, systematic assessment for liver fibrosis in those with HCV infection and institution of antivirals to prevent advanced liver disease.Chronic hepatitis C virus (HCV) infection is a major cause of cirrhosis, creatingalarge public health burden. Based on the US National Health and Nutrition Examination Survey sample, we found the proportion of patients with cirrhosis among Americans with HCV infection increased from 6.6% to 17.0% over the past two decades. Patients who wereunaware of their infection was just as likely to have cirrhosis as those who knew about their infection,which highlights the need for screening and treatment for HCV at the population level.

    View details for DOI 10.1016/j.jhep.2016.01.009

    View details for PubMedID 26809112

  • Epidemiology and Healthcare Burden of Acute-on-Chronic Liver Failure SEMINARS IN LIVER DISEASE Allen, A. M., Kim, W. R. 2016; 36 (2): 123-126


    Chronic liver disease and cirrhosis, a common end result of viral hepatitis, alcohol abuse, and the emerging epidemic of nonalcoholic fatty liver disease are a significant source of morbidity and premature mortality globally. Acute clinical deterioration of chronic liver disease exemplifies the pinnacle of healthcare burden due to the intensive medical needs and high mortality risk. Although a uniformly accepted definition for epidemiological studies is lacking, acute-on-chronic liver failure (ACLF) is increasingly recognized as an important source of disease burden. At least in the United States, hospitalizations for ACLF have increased several fold in the last decade and have a high fatality rate. Acute-on-chronic liver failure incurs extremely high costs, exceeding the yearly costs of inpatient management of other common medical conditions. Although further epidemiological data are needed to better understand the true impact and future trends of ACLF, these data point to the urgency in the clinical investigation for ACLF and the deployment of healthcare resources for timely and effective interventions in affected patients.

    View details for DOI 10.1055/s-0036-1583201

    View details for Web of Science ID 000375823100004

    View details for PubMedID 27172353

  • Evaluation of APRI and FIB-4 scoring systems for non-invasive assessment of hepatic fibrosis in chronic hepatitis B patients JOURNAL OF HEPATOLOGY Kim, W. R., Berge, T., Asselah, T., Flisiak, R., Fung, S., Gordon, S. C., Janssens, H. L., Lampertico, P., Lau, D., Bornstein, J. D., Schall, R. E., Dinh, P., Yee, L. J., Martins, E. B., Lim, S. G., Loomba, R., Petersen, J., Buti, M., Marcellin, P. 2016; 64 (4): 773-780
  • Evaluation of APRI and FIB-4 scoring systems for non-invasive assessment of hepatic fibrosis in chronic hepatitis B patients. Journal of hepatology Kim, W. R., Berg, T., Asselah, T., Flisiak, R., Fung, S., Gordon, S. C., Janssen, H. l., Lampertico, P., Lau, D., Bornstein, J. D., Schall, R. E., Dinh, P., Yee, L. J., Martins, E. B., Lim, S. G., Loomba, R., Petersen, J., Buti, M., Marcellin, P. 2016; 64 (4): 773-780


    While the gold standard in the assessment of liver fibrosis remains liver biopsy, non-invasive methods have been increasingly used for chronic hepatitis B (CHB). This study aimed to evaluate the performance of two commonly used non-invasive scoring systems (aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4)) to predict fibrosis stage in CHB patients.Demographic, histologic and clinical laboratory data from two trials investigating tenofovir disoproxil fumarate in CHB were analyzed. Predicted fibrosis stage, based on established scales and cut-off values for APRI and FIB-4 scores, was compared with Ishak scores obtained from liver biopsy at baseline and at 240week follow-up.In the 575 patients with a baseline liver biopsy, APRI and FIB-4 scores correlated with Ishak stage (p<0.01); however extensive overlap in the distribution of both scores across Ishak stages prevented accurate determination of fibrosis. The majority (81-89%) of patients with advanced fibrosis or cirrhosis were missed by the scores. Similarly, 71% patients without fibrosis were misclassified as having clinically significant fibrosis. APRI and FIB-4 scores at week 240 tended to be low and underestimate fibrosis stage in the patients with liver biopsies after 240weeks of therapy. APRI or FIB-4 reduction did not correlate with fibrosis regression after 240weeks of antiviral therapy.APRI and FIB-4 scores are not suitable for use in clinical practice in CHB patients for assessment of hepatic fibrosis according to Ishak stage, especially in gauging improvements in liver fibrosis following therapy.

    View details for DOI 10.1016/j.jhep.2015.11.012

    View details for PubMedID 26626497

  • Hepatitis B Virus-Specific and Global T-Cell Dysfunction in Chronic Hepatitis B GASTROENTEROLOGY Park, J., Wong, D. K., Wahed, A. S., Lee, W. M., Feld, J. J., Terrault, N., Khalili, M., Sterling, R. K., Kowdley, K. V., Bzowej, N., Lau, D. T., Kim, W. R., Smith, C., Carithers, R. L., Torrey, K. W., Keith, J. W., Levine, D. L., Traum, D., Ho, S., Valiga, M. E., Johnson, G. S., Doo, E., Lok, A. S., Chang, K. 2016; 150 (3): 684-?


    T cells play a critical role in viral infection. We examined whether T-cell effector and regulatory responses can define clinical stages of chronic hepatitis B (CHB).We enrolled 200 adults with CHB who participated in the National Institutes of Health-supported Hepatitis B Research Network from 2011 through 2013 and 20 uninfected individuals (controls). Peripheral blood lymphocytes from these subjects were analyzed for T-cell responses (proliferation and production of interferon gamma and interleukin 10) to overlapping hepatitis B virus (HBV) peptides (preS, S, preC, core, and reverse transcriptase), influenza matrix peptides, and lipopolysaccharide. T-cell expression of regulatory markers FOXP3, programmed death-1, and cytotoxic T lymphocyte-associated antigen-4 was examined by flow cytometry. Immune measures were compared with clinical parameters, including physician-defined immune-active, immune-tolerant, or inactive CHB phenotypes, in a blinded fashion.Compared with controls, patients with CHB had weak T-cell proliferative, interferon gamma, and interleukin 10 responses to HBV, with increased frequency of circulating FOXP3(+)CD127(-) regulatory T cells and CD4(+) T-cell expression of programmed death-1 and cytotoxic T lymphocyte-associated antigen-4. T-cell measures did not clearly distinguish between clinical CHB phenotypes, although the HBV core-specific T-cell response was weaker in hepatitis B e antigen (HBeAg)(+) than HBeAg(-) patients (percent responders: 3% vs 23%; P = .00008). Although in vitro blockade of programmed death-1 or cytotoxic T lymphocyte-associated antigen-4 increased T-cell responses to HBV, the effect was weaker in HBeAg(+) than HBeAg(-) patients. Furthermore, T-cell responses to influenza and lipopolysaccharide were weaker in CHB patients than controls.HBV persists with virus-specific and global T-cell dysfunction mediated by multiple regulatory mechanisms, including circulating HBeAg, but without distinct T-cell-based immune signatures for clinical phenotypes. These findings suggest additional T-cell-independent or regulatory mechanisms of CHB pathogenesis that warrant further investigation.

    View details for DOI 10.1053/j.gastro.2015.11.050

    View details for Web of Science ID 000370648100029

    View details for PubMedID 26684441

    View details for PubMedCentralID PMC4766024

  • The Epidemiology of Liver Diseases Unique to Pregnancy in a US Community: A Population-Based Study CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Allen, A. M., Kim, W. R., Larson, J. J., Rosedahl, J. K., Yawn, B. P., McKeon, K., Hay, J. E. 2016; 14 (2): 287-?


    Little is known in the United States about the epidemiology of liver diseases that develop only during (are unique to) pregnancy. We investigated the incidence of liver diseases unique to pregnancy in Olmsted County, Minnesota, and long-term maternal and fetal outcomes.We identified 247 women with liver diseases unique to pregnancy from 1996 through 2010 using the Rochester Epidemiology Project database. The crude incidence rate was calculated by the number of liver disease cases divided by 35,101 pregnancies.Of pregnant women with liver diseases, 134 had preeclampsia with liver dysfunction, 72 had hemolysis-associated increased levels of liver enzymes and low-platelet (HELLP) syndrome, 26 had intrahepatic cholestasis of pregnancy, 14 had hyperemesis gravidarum with abnormal liver enzymes, and 1 had acute fatty liver of pregnancy. The crude incidence of liver diseases unique to pregnancy was 0.77%. Outcomes were worse among women with HELLP or preeclampsia than the other disorders--of women with HELLP, 70% had a premature delivery, 4% had abruptio placentae, 3% had acute kidney injury, and 3% had infant death. Of women with preeclampsia, 56.0% had a premature delivery, 4% had abruptio placentae, 3% had acute kidney injury, and 0.7% had infant death. After 7 median years of follow-up (range, 0-18 years), 14% of the women developed recurrent liver disease unique to pregnancy; the proportions were highest in women with initial hyperemesis gravidarum (36%) or intrahepatic cholestasis of pregnancy (35%). Women with preeclampsia were more likely to develop subsequent hepatobiliary diseases.We found the incidence of liver disease unique to pregnancy in Olmsted County, Minnesota, to be lower than that reported from Europe or US tertiary referral centers. Maternal and fetal outcomes in Olmsted County were better than those reported from other studies, but fetal mortality was still high (0.7%-3.0%). Women with preeclampsia or HELLP are at higher risk for peripartum complications and subsequent development of comorbidities.

    View details for DOI 10.1016/j.cgh.2015.08.022

    View details for Web of Science ID 000370376300023

    View details for PubMedID 26305066

    View details for PubMedCentralID PMC4718803

  • Entecavir safety and effectiveness in a national cohort of treatment-naive chronic hepatitis B patients in the US - the ENUMERATE study ALIMENTARY PHARMACOLOGY & THERAPEUTICS Ahn, J., Lee, H. M., Lim, J. K., Pan, C. Q., Nguyen, M. H., Kim, W. R., Mannalithara, A., Trinh, H., Chu, D., Tran, T., Min, A., Do, S., Te, H., Reddy, K. R., Lok, A. S. 2016; 43 (1): 134-144


    Entecavir (ETV) has been shown to be safe and efficacious in randomised controlled trials in highly selected patients with hepatitis B virus (HBV) infection.To determine the safety and effectiveness of ETV in 'real-world' HBV patients in the United States (US).Treatment-naïve HBV patients ≥18 years old who received ETV for ≥12 months between 2005 and 2013 were included in a retrospective, cohort study. Rates of ALT normalisation, undetectable HBV DNA, HBeAg and HBsAg loss/seroconversion, adverse events (AE) and clinical outcomes were evaluated.Of 841 patients, 658 [65% male, 83% Asian; median age 47 years] met the inclusion criteria. 36% were HBeAg+ and 9.3% cirrhotic. 89% had abnormal ALT. Baseline median HBV DNA was 5.8 log 10 IU/mL. Median duration of ETV treatment was 4 years. Rates of ALT normalisation at 1, 3 and 5 years were 37.2%, 48.7% and 56.2% in HBeAg+ and 39.6%, 46.8% and 55.6% in HBeAg- patients. HBV DNA was undetectable at 1, 3 and 5 years in 34.6%, 64.7% and 84.6% in HBeAg+ patients, and 81.9%, 90.3% and 96.2% in HBeAg patients. Five-year cumulative probability of HBeAg loss and seroconversion was 46% and 33.7% and HBsAg loss was 4.6%. ETV was discontinued due to adverse events in 1.2% of patients. Hepatic decompensation occurred in 0.8%, liver cancer in 2.7% and death in 0.6%.Entecavir treatment was safe in a large cohort of US patients, but ALT normalisation and hepatitis B virus DNA suppression rates were lower than previously reported in clinical trials.

    View details for DOI 10.1111/apt.13440

    View details for Web of Science ID 000368188100013

    View details for PubMedCentralID PMC4926997

  • Current and Future Burden of Chronic Nonmalignant Liver Disease. Clinical gastroenterology and hepatology Udompap, P., Kim, D., Kim, W. R. 2015; 13 (12): 2031-2041


    Disease burden is an important indicator of the state of health of a population. It can be measured as the frequency (eg, incidence and prevalence) of a condition or its effects including fatal and non-fatal health loss from disease (eg, disability-adjusted life years) as well as the financial costs (eg, direct healthcare costs and indirect healthcare expenditures related to lost income because of premature death). Accurate disease burden information is essential for policy-making such as prioritization of health interventions and allocation of resources. Chronic liver disease (CLD) causes substantial health and economic burden in the United States, where nearly 2 million deaths annually are attributable to CLD. In the recent past, overall mortality rate of CLD has been increasing. Viral hepatitis and alcoholic liver disease are thought to be the most common etiologies of chronic liver diseases. More recently, the prevalence of nonalcoholic fatty liver disease is rapidly increasing, and nonalcoholic steatohepatitis has become a leading indication for liver transplantation. In this article, we assemble available data on the burden of CLD in the United States, focusing on nonmalignant complications, whereas the impact on mortality and healthcare expenses of hepatocellular carcinoma, an important consequence of CLD, is discussed elsewhere.

    View details for DOI 10.1016/j.cgh.2015.08.015

    View details for PubMedID 26291665

  • Diabetes and prediabetes in patients with hepatitis B residing in North America HEPATOLOGY Khalili, M., Lombardero, M., Chung, R. T., Terrault, N. A., Ghany, M. G., Kim, W. R., Lau, D., Lisker-Melman, M., Sanyal, A., Lok, A. S. 2015; 62 (5): 1364-1374


    Diabetes is associated with liver disease progression and increased hepatocellular carcinoma risk, but factors associated with diabetes in patients with chronic hepatitis B virus (HBV) infection in North America are unknown. We aimed to determine factors predictive of diabetes and impaired fasting glucose (IFG) in a large HBV-infected multiethnic cohort. Adults with chronic HBV not receiving antiviral therapy were enrolled from 21 centers in North America. Diabetes was defined by history/medication use or fasting glucose≥126 mg/dL and IFG as fasting glucose 100-125 mg/dL. Of 882 patients included, 47.2% were female, 71.3% Asian, 83.7% foreign born, median age was 44 years, and median body mass index BMI 24.3 kg/m2. In this cohort, 26.0% were hepatitis B envelope antigen (HBeAg) positive, 43.9% had HBV DNA≥20,000 IU/mL, and 26.7% alanine aminotransferase (ALT)≥2× upper limit of normal (≥40 U/L women, ≥60 U/L men). Overall, 12.5% had diabetes and 7.8% IFG. The combined prevalence of diabetes or IFG was highest among blacks (36.7%) and those either born in the United States/Canada or foreign born with migration>20 years ago (25.5%). Obesity (odds ratio [OR]: 2.13), hyperlipidemia (OR, 4.13), hypertension (OR, 3.67), high ALT level (OR, 1.86), and family history of diabetes (OR, 3.43) were associated with diabetes. Factors associated with IFG were obesity (OR, 4.13) and hypertension (OR, 3.27), but also HBeAg positivity (OR, 0.39). Recent migration was negatively associated with diabetes among non-Asians (OR, 0.30).Diabetes is more prevalent in HBV-infected North American adults than the general population and is associated with known metabolic risk factors and liver damage, as determined by ALT levels. Among the foreign born, longer duration of North America residence predicted diabetes risk in non-Asians. These results highlight the opportunities for interventions to prevent diabetes especially among at-risk ethnic groups with HBV.

    View details for DOI 10.1002/hep.28110

    View details for Web of Science ID 000363264100008

    View details for PubMedID 26390278

  • Korean Version of a Model to Estimate Survival in Ambulatory Patients with Hepatocellular Carcinoma (K-MESIAH) PLOS ONE Nam, B., Park, J., Jeong, S., Lee, S. S., Yu, A., Kim, B. H., Kim, W. R. 2015; 10 (10)

    View details for DOI 10.1371/journal.pone.0138374

    View details for Web of Science ID 000363248400006

    View details for PubMedID 26488298

  • Impact of Long-Term Tenofovir Disoproxil Fumarate on Incidence of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B CANCER Kim, W. R., Loomba, R., Berg, T., Schall, R. E., Yee, L. J., Dinh, P. V., Flaherty, J. F., Martins, E. B., Therneau, T. M., Jacobson, I., Fung, S., Gurel, S., Buti, M., Marcellin, P. 2015; 121 (20): 3631-3638

    View details for DOI 10.1002/cncr.29537

    View details for Web of Science ID 000363262700011

  • Serum Cystatin Cas an Indicator of Renal Function and Mortality in Liver Transplant Recipients TRANSPLANTATION Allen, A. M., Kim, W. R., Larson, J. J., Colby, C., Therneau, T. M., Rule, A. D. 2015; 99 (7): 1431-1435


    Chronic kidney disease (CKD) is an important comorbidity after liver transplantation (LT); however, reliable tools with which to evaluate these patients are limited. In this work, we examine the extent to which the addition of serum cystatin C improves glomerular filtration rate (GFR) estimation and mortality prediction, in comparison to various GFR-estimating equations.The GFR was measured in LT recipients by iothalamate clearance. Concurrent serum cystatin C was assayed in banked serum samples. Performance of GFR-estimating equations with and without cystatin C, including the modification of diet in renal disease and CKD-epidemiology collaboration formulas was assessed. The proportional hazards regression analysis was performed to determine the association between serum cystatin C and mortality.A total of 586 iothalamate results were obtained in 401 patients after a mean of 4 years after LT. When compared to measured GFR, the formula with both creatinine and cystatin C, namely, CKD-epidemiology cr-cys, outperformed those with either marker alone. Performance of creatinine-based models was similar to one another. Serum cystatin C, by itself or as a part of an estimated GFR, was a significant predictor of mortality.Serum cystatin C has an important role in enhancing accuracy of GFR estimation and predicting mortality in LT recipients.

    View details for DOI 10.1097/TP.0000000000000552

    View details for Web of Science ID 000369083200026

    View details for PubMedID 25654627

    View details for PubMedCentralID PMC4551433

  • Delayed Hepatocellular Carcinoma Model for End-Stage Liver Disease Exception Score Improves Disparity in Access to Liver Transplant in the United States HEPATOLOGY Heimbach, J. K., Hirose, R., Stock, P. G., Schladt, D. P., Xiong, H., Liu, J., Olthoff, K. M., Harper, A., Snyder, J. J., Israni, A. K., Kasiske, B. L., Kim, W. R. 2015; 61 (5): 1643-1650


    The current system granting liver transplant candidates with hepatocellular carcinoma (HCC) additional Model for End-Stage Liver Disease (MELD) points is controversial due to geographic disparity and uncertainty regarding optimal prioritization of candidates. The current national policy assigns a MELD exception score of 22 immediately upon listing of eligible patients with HCC. The aim of this study was to evaluate the potential effects of delays in granting these exception points on transplant rates for HCC and non-HCC patients. We used Scientific Registry of Transplant Recipients data and liver simulated allocation modeling software and modeled (1) a 3-month delay before granting a MELD exception score of 25, (2) a 6-month delay before granting a score of 28, and (3) a 9-month delay before granting a score of 29. Of all candidates waitlisted between January 1 and December 31, 2010 (n = 28,053), 2773 (9.9%) had an HCC MELD exception. For HCC candidates, transplant rates would be 108.7, 65.0, 44.2, and 33.6 per 100 person-years for the current policy and for 3-, 6-, and 9-month delays, respectively. Corresponding rates would be 30.1, 32.5, 33.9, and 34.8 for non-HCC candidates.A delay of 6-9 months would eliminate the geographic variability in the discrepancy between HCC and non-HCC transplant rates under current policy and may allow for more equal access to transplant for all candidates.

    View details for DOI 10.1002/hep.27704

    View details for Web of Science ID 000353233500023

    View details for PubMedID 25644186

  • Low Level of Hepatitis B Virus Screening Among Patients Receiving Chemotherapy CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Wi, C., Loo, N. M., Larson, J. J., Moynihan, T. J., Madde, N. R., Grendahl, D. C., Alberts, S. R., Kim, W. R. 2015; 13 (5): 970-975


    Chemotherapy of patients with inactive hepatitis B virus (HBV) infection can lead to viral reactivation and hepatitis flares. We investigated the proportion of patients screened for HBV infection before chemotherapy over time and the outcomes of screened patients.In a retrospective study, we collected data from a pharmacy database on patients who underwent cytotoxic chemotherapy for solid or hematologic malignancies at the Mayo Clinic in Rochester, Minnesota, from January 1, 2006, through September 30, 2011. Laboratory data were collected from electronic medical records. Screening was identified based on tests for hepatitis B surface antigen, for any reason at any time before chemotherapy.Of 8005 patients undergoing chemotherapy, 1279 (16%) were screened for HBV infection before chemotherapy, including 668 of 1805 patients with hematologic malignancies (37%). The proportion of patients screened for HBV increased from 14.3% in 2006 to 2008 to 17.7% in 2009 to 2011 (P < .01). This trend was attributed mostly to an increase in the proportion of patients with hematologic malignancies, from 32.7% in 2006 to 2008 to 40.6% in 2009 to 2011 (P < .01). Of 13 patients who tested positive for HBV, 5 did not receive prophylactic antiviral therapy; HBV infection was reactivated in 2 of these patients. None of the 8 patients who received an antiviral agent before chemotherapy experienced HBV reactivation. Of 58 unscreened patients who had increases in their alanine aminotransferase level (>300 U/L), only 1 patient appeared to have an undiagnosed HBV infection.Only a small percentage of patients receiving chemotherapy are screened for HBV infection. However, a larger proportion of patients was screened during 2009 to 2011 than during 2006 to 2008, especially patients with hematologic malignancies. Strategies are needed to ensure that patients receiving chemotherapy are protected from the consequences of undiagnosed HBV infection.

    View details for DOI 10.1016/j.cgh.2014.10.032

    View details for Web of Science ID 000353069000028

    View details for PubMedID 25460017

    View details for PubMedCentralID PMC4547834

  • Sofosbuvir and simeprevir combination therapy in the setting of liver transplantation and hemodialysis TRANSPLANT INFECTIOUS DISEASE Perumpail, R. B., Wong, R. J., Ha, L. D., Pham, E. A., Wang, U., Luong, H., Kumari, R., Daugherty, T. J., Higgins, J. P., Younossi, Z. M., Kim, W. R., Glenn, J. S., Ahmed, A. 2015; 17 (2): 275-278


    We report safety, tolerability, and 12-week sustained virologic response with half-standard dose sofosbuvir and standard-dose simeprevir combination therapy in a hepatitis C virus genotype 1a-infected liver transplant recipient on hemodialysis - uncharted territory for sofosbuvir-based therapy. The patient was a non-responder to prior treatment with pegylated interferon plus ribavirin. Sofosbuvir efficacy was maintained despite pill-splitting and administration of half-standard dose, 200 mg per day. No drug-drug interactions were noted with tacrolimus-based immunosuppression. Laboratory tests remained stable or improved during therapy. Our observation, if reproduced in a larger study, may lead to significant improvement in clinical outcomes and cost savings in this patient population.

    View details for DOI 10.1111/tid.12348

    View details for Web of Science ID 000352219400013

    View details for PubMedID 25641426

  • Characteristics of Adults in the Hepatitis B Research Network in North America Reflect Their Country of Origin and Hepatitis B Virus Genotype CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Ghany, M. G., Perrillo, R., Li, R., Belle, S. H., Janssen, H. l., Terrault, N. A., Shuhart, M. C., Lau, D. T., Kim, W. R., Fried, M. W., Sterling, R. K., Di Bisceglie, A. M., Han, S. B., Ganova-Raeva, L. M., Chang, K., Lok, A. S. 2015; 13 (1): 183-192


    Chronic hepatitis B virus (HBV) infection is an important cause of cirrhosis and hepatocellular carcinoma worldwide; populations that migrate to the United States and Canada might be affected disproportionately. The Hepatitis B Research Network (HBRN) is a cooperative network of investigators from the United States and Canada, created to facilitate clinical, therapeutic, and translational research in adults and children with hepatitis B. We describe the structure of the network and baseline characteristics of adults with hepatitis B enrolled in the network.The HBRN collected data on the clinical characteristics of 1625 adults with chronic HBV infection who are not receiving antiviral therapy from 21 clinical centers in North America.Half of the subjects in the HBRN are men, and the median age is 42 years; 72% are Asian, 15% are black, and 11% are white; with 82% born outside of North America. The most common HBV genotype was B (39%); 74% of subjects were negative for the hepatitis B e antigen. The median serum level of HBV DNA when the study began was 3.6 log10 IU/mL; 68% of male subjects and 67% of female subjects had alanine aminotransferase levels higher than the normal range.The HBRN cohort is used to address important clinical and therapeutic questions for North Americans infected with chronic HBV and to guide health policies on HBV prevention and management in North America.

    View details for DOI 10.1016/j.cgh.2014.06.028

    View details for Web of Science ID 000348040500032

    View details for PubMedID 25010003

  • Risk Prediction of Hepatocellular Carcinoma in Patients With Cirrhosis: The ADRESS-HCC Risk Model CANCER Flemming, J. A., Yang, J. D., Vittinghoff, E., Kim, W. R., Terrault, N. A. 2014; 120 (22): 3485-3493


    All patients with cirrhosis are at risk of developing hepatocellular carcinoma (HCC). This risk is not uniform because other patient-related factors influence the risk of HCC. The objective of the current study was to develop an HCC risk prediction model to estimate the 1-year probability of HCC to assist with patient counseling.Between 2002 and 2011, a cohort of 34,932 patients with cirrhosis was identified from a national liver transplantation waitlist database from the United States. Cox proportional hazards regression methods were used to develop and validate a risk prediction model for incident HCC. In the validation cohort, discrimination and calibration of the model was examined. External validation was conducted using patients with cirrhosis who were enrolled in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) study.HCC developed in 1960 patients (5.6%) during a median follow-up of 1.3 years (interquartile range, 0.47 years-2.83 years). Six baseline clinical variables, including age, diabetes, race, etiology of cirrhosis, sex, and severity (ADRESS) of liver dysfunction were independently associated with HCC and were used to develop the ADRESS-HCC risk model. C-indices in the derivation and internal validation cohorts were 0.704 and 0.691, respectively. In the validation cohort, the predicted cumulative incidence of HCC by the ADRESS-HCC model closely matched the observed data. In patients with cirrhosis in the HALT-C cohort, the model stratified patients correctly according to the risk of developing HCC within 5 years.The ADRESS-HCC risk model is a useful tool for predicting the 1-year risk of HCC among patients with cirrhosis.

    View details for DOI 10.1002/cncr.28832

    View details for Web of Science ID 000344650900010

    View details for PubMedID 25042049

    View details for PubMedCentralID PMC4553222

  • Chronic kidney disease and associated mortality after liver transplantation - A time-dependent analysis using measured glomerular filtration rate JOURNAL OF HEPATOLOGY Allen, A. M., Kim, W. R., Therneau, T. M., Larson, J. J., Heimbach, J. K., Rule, A. D. 2014; 61 (2): 286-292


    The accuracy of creatinine-based estimated GFR (eGFR) in assessing the prevalence of chronic kidney disease (CKD) and associated mortality after liver transplantation (LTx) is unknown. Using measured GFR (mGFR) by iothalamate clearance, we determined the prevalence of the entire spectrum of renal dysfunction and the impact of CKD on mortality after LTx.A database that prospectively tracks all LTx recipients at this academic transplant program from 1985 to 2012 was queried to identify all adult primary LTx recipients. Our post-LTx protocol incorporates GFR measurement by iothalamate clearance at regular intervals. A multistate model was used to assess the prevalence of CKD, kidney transplant, and death after LTx. Time-dependent Cox regression analysis was performed to evaluate the impact of mGFR and eGFR changes on survival.A total of 1211 transplant recipients were included. At the time of LTx, the median age was 54 years, 60% were male and 86% were Caucasian. At 25 years after LTx, 54% of patients died, 9% underwent kidney transplantation, whereas 7%, 21%, and 18% had mGFR >60, 59-30, and <30 ml/min/1.73 m(2) respectively. The risk of death increased when mGFR decreased below 30 ml/min/1.73 m(2): HR = 2.67 (95% CI = 1.80-3.96) for GFR = 29-15 ml/min/1.73 m(2) and HR = 5.47 (95% CI = 3.10-9.65) for GFR <15 ml/min/1.73 m(2). Compared to mGFR, eGFR underestimated mortality risk in LTx recipients with an eGFR of 30-90 ml/min/1.73 m(2).An overwhelming majority of LTx recipients develop CKD. The risk of death increases exponentially when GFR <30 ml/min/1.73 m(2). Creatinine-based eGFR underestimates the mortality risk in a large proportion of patients.

    View details for DOI 10.1016/j.jhep.2014.03.034

    View details for Web of Science ID 000339775700017

    View details for PubMedID 24713190

  • Validation of a model to estimate survival in ambulatory patients with hepatocellular carcinoma: a single-centre cohort study LIVER INTERNATIONAL Kim, B. H., Park, J., Nam, B., Kwak, H. W., Kim, W. R. 2014; 34 (7): E317-E323


    Survival of patients with hepatocellular carcinoma (HCC) is determined by hepatic function and tumour extent. Recently, a new Model to Estimate Survival in Ambulatory HCC patients (MESIAH) was proposed to predict overall survival in ambulatory HCC patients. This study aimed to evaluate the prognostic performance of the MESIAH score in an independent cohort of HCC patients.A cohort of 1969 patients newly diagnosed with HCC at the National Cancer Center, Korea between January 2004 and December 2009 was used for validation of the MESIAH score. The model's performance was assessed using C-statistics, the likelihood ratio (LR) χ2 value and Akaike information criterion (AIC).Patients in the cohort had a median age of 56 years and 83.2% were men. Hepatitis B virus infection was present in 74.6 and 81.6% had a Child-Pugh class A. The median overall survival was 21.4 months. The MESIAH score had a higher degree of discrimination, with a C-statistic of 0.792 [95% confidence interval (CI), 0.782-0.803], when compared with the Barcelona Clinic Liver Cancer (BCLC) staging system [0.665 (95% CI, 0.653-0.678), P<0.001]. The LR χ2 value and the AIC of MESIAH were also better than those of BCLC, Cancer of the Liver Italian Program, Japan Integrated Scoring and Tokyo score. The observed survival in the cohort closely matched that predicted by the MESIAH score.The new prognostication model MESIAH accurately estimated the overall survival of Korean HCC patients and may be useful in future research as well as individual patient care.

    View details for DOI 10.1111/liv.12519

    View details for Web of Science ID 000339723900017

    View details for PubMedID 24606128

  • Effect of the Pretransplant Serum Sodium Concentration on Outcomes Following Liver Transplantation LIVER TRANSPLANTATION Leise, M. D., Yun, B. C., Larson, J. J., Benson, J. T., Yang, J. D., Therneau, T. M., Rosen, C. B., Heimbach, J. K., Biggins, S. W., Kim, W. R. 2014; 20 (6): 687-697


    Hyponatremia is associated with an increased risk of mortality on the liver transplantation (LT) waiting list. Although the incorporation of the serum sodium (Na) level into the Model for End-Stage Liver Disease score may reduce wait-list mortality, concerns remain about a potential association between pre-LT hyponatremia and decreased post-LT survival. Furthermore, the relationship between pre-LT hypernatremia and post-LT survival remains unexplored. The purpose of this study was to investigate the impact of the entire spectrum of pre-LT serum Na levels on post-LT outcomes. We identified 19,537 patients from 2003 to 2010 for whom serum Na levels immediately before LT were available. The patients were divided into 3 groups [hyponatremic (Na ≤ 130 mEq/L), normonatremic (Na = 131-145 mEq/L), and hypernatremic (Na > 145 mEq/L)], and their post-LT outcomes were compared. There was no difference in in-hospital mortality or 90-day survival between patients with hyponatremia and patients with normonatremia. A fraction of the patients (2.4%) had hypernatremia, which was associated with increased in-hospital mortality (11.2% versus 4.2%, P < 0.001) and diminished 90-day survival (86.4% versus 94.0.%, P < 0.001). After adjustments for important clinical variables, the association of pre-LT hypernatremia with posttransplant mortality remained significant with a hazard ratio of 1.13 for each unit increase in the Na level > 145 mEq/L (P < 0.001). The duration of the hospitalization after LT was significantly longer for hypernatremic patients (P < 0.001). In conclusion, hyponatremia per se does not affect post-LT survival. Pre-LT hypernatremia is a highly significant risk factor for post-LT mortality.

    View details for DOI 10.1002/lt.23860

    View details for Web of Science ID 000340191200009

    View details for PubMedID 24616214

  • Comparative Effectiveness of Telaprevir-Based Triple Therapy in Patients With Chronic Hepatitis C MAYO CLINIC PROCEEDINGS Al-Bawardy, B., Kim, W. R., Poterucha, J. J., Gross, J. B., Charlton, M. R., Larson, J. J., Colby, C. L., Canterbury, K., Warner, J., Therneau, T. M. 2014; 89 (5): 595-601


    To examine the effectiveness and tolerability of triple therapy with pegylated interferon (p-IFN), ribavirin (RBV), and telaprevir in patients with chronic hepatitis C receiving treatment in an academic practice setting and in a more clinically diverse population compared with patients receiving treatment in phase 3 trials.A prospective database of all patients with viral hepatitis undergoing antiviral therapy from January 1, 2006, to July 1, 2012, was queried to identify treatment-naive and -experienced patients with chronic hepatitis C receiving dual and triple therapies. On-treatment response categories included rapid virologic response, extended rapid virologic response, early virologic response, and sustained virologic response. These patients were compared with matched controls, namely, patients who underwent dual therapy with p-IFN and RBV. Matching was performed for age, cirrhosis status, and prior treatment.There were 55 patients who received triple therapy and met the eligibility criteria, consisting of treatment-naive (n=35) and -experienced patients (n=20: those with relapse, 9; those with nonresponse, 9; and those who terminated the treatment early, 2). Rapid virologic response was achieved in 41% of the patients, extended rapid virologic response in 41%, and early virologic response in 75%. Sustained virologic response was observed in 51% (18/35) of treatment-naive patients, 67% (6/9) of the patients with prior nonresponse, and 56% (5/9) of those with prior relapse. Corresponding results after dual therapy were 37% (23/62), 11% (2/18), and 27% (3/11), respectively. The mean decrease in the hemoglobin level at weeks 4, 8, and 24 of triple therapy was 2.8, 3.8, and 3.2 mg/dL compared with 2.4, 2.6, and 2.4 mg/dL with dual therapy (to convert mg/dL to mmol/L, multiply values by 0.0259).Telaprevir-based triple therapy in clinical practice is considerably more effective than dual therapy with p-IFN and RBV despite the significant degree of anemia that complicated therapy, requiring RBV dose reduction and erythropoietin support.

    View details for DOI 10.1016/j.mayocp.2014.01.024

    View details for Web of Science ID 000335560400006

    View details for PubMedID 24661475

  • Survival of Recipients of Livers From Donation After Circulatory Death Who Are Relisted and Undergo Retransplant for Graft Failure AMERICAN JOURNAL OF TRANSPLANTATION Allen, A. M., Kim, W. R., Xiong, H., Liu, J., Stock, P. G., Lake, J. R., Chinnakotla, S., Snyder, J. J., Israni, A. K., Kasiske, B. L. 2014; 14 (5): 1120-1128


    Use of grafts from donation after circulatory death (DCD) as a strategy to increase the pool of transplantable livers has been limited due to poorer recipient outcomes compared with donation after brain death (DBD). We examined outcomes of recipients of failed DCD grafts who were selected for relisting with regard to waitlist mortality and patient and graft survival after retransplant. From the Scientific Registry of Transplant Recipients database, we identified 1820 adults who underwent first deceased donor liver transplant January 1, 2004 to June 30, 2011, and were relisted due to graft failure; 12.7% were DCD recipients. Compared with DBD recipients, DCD recipients had better waitlist survival (90-day mortality: 8%, DCD recipients; 14-21%, DBD recipients). Of 950 retransplant patients, 14.5% were prior DCD recipients. Graft survival after second liver transplant was similar for prior DCD (28% graft failure within 1 year) and DBD recipients (30%). Patient survival was slightly better for prior DCD (25% death within 1 year) than DBD recipients (28%). Despite higher overall graft failure and morbidity rates, survival of prior DCD recipients who were selected for relisting and retransplant was not worse than survival of DBD recipients.

    View details for DOI 10.1111/ajt.12700

    View details for Web of Science ID 000334404900017

    View details for PubMedID 24731165

  • The impact of hepatitis C burden: an evidence-based approach ALIMENTARY PHARMACOLOGY & THERAPEUTICS Younossi, Z. M., Kanwal, F., Saab, S., Brown, K. A., El-Serag, H. B., Kim, W. R., Ahmed, A., Kugelmas, M., Gordon, S. C. 2014; 39 (5): 518-531


    Infection with the hepatitis C virus (HCV) has been considered a major cause of mortality, morbidity and resource utilisation in the US. In addition, HCV is the main cause of hepatocellular cancer (HCC) in the US. Recent developments in the diagnosis and treatment of HCV, including new recommendations pertaining to screening for HCV by the Centers for Disease Control and Prevention and newer treatment regimens with high efficacy, short duration and the potential for interferon-free therapies, have energised the health care practitioners regarding HCV management.To assess the full impact of HCV burden on clinical, economic and patient-reported outcomes.An expert panel was convened to assess the full impact of HCV burden on a number of important outcomes using an evidence-based approach predicated on Grading of Recommendations Assessment, Development and Evaluation methodology. The literature was summarised, graded using an evidence-based approach and presented during the workshop. Workshop presentations were intended to review recent, relevant evidence-based literature and provide graded summary statements pertaining to HCV burden on topics including the relationships between HCV and the development of important outcomes.The associations of HCV with cirrhosis, HCC, liver-related mortality, type 2 diabetes mellitus, rheumatological diseases and quality of life impairments are supported by strong evidence. Also, there is strong evidence that sustained viral eradication of HCV can improve important outcomes such as mortality and quality of life.The current evidence suggests that HCV has been associated with tremendous clinical, economic and quality of life burden.

    View details for DOI 10.1111/apt.12625

    View details for Web of Science ID 000330564900007

    View details for PubMedID 24461160

  • Management of Hepatic Encephalopathy in the Hospital MAYO CLINIC PROCEEDINGS Leise, M. D., Poterucha, J. J., Kamath, P. S., Kim, W. R. 2014; 89 (2): 241-253


    Hepatic encephalopathy (HE) develops in up to 50% of patients with cirrhosis and is a feature of decompensated cirrhosis. With the goal of reviewing the evidence for treatment and prevention of overt hepatic encephalopathy, pubmed was searched using search terms hepatic encephalopathy AND treatment, limited to human studies from January 1, 2003, through December 1, 2013, and supplemented by key references. The inpatient incidence of HE is approximately 23,000 annually, and management of these patients is common for internists and subspecialists. Treatment of the hospitalized patient with HE has changed in recent years. Treatment entails 2 phases: induction and maintenance of remission. Most cases of significant HE are precipitated by infection, gastrointestinal bleeding, medications, or other culprits. All patients should be evaluated for secondary triggers of HE, and treatment should be initiated with a nonabsorbable disaccharide (ie, lactulose) in most patients. Rifaximin (off label) can be added in patients not responding to lactulose. Neomycin is a less preferred alternative to rifaximin owing to its adverse effect profile. Other therapies, including zinc, L-ornithine-L-aspartate, and branched-chain amino acids, can be considered for patients not responding to disaccharides and nonabsorbable antibiotics. Large portosystemic shunts may be embolized in patients with medically refractory recurrent or severe HE with otherwise well-compensated cirrhosis. Molecular Adsorbent Recirculating System is now available for patients with severe HE who do not respond to medical therapy. It is critically important that patients hospitalized with significant HE continue maintenance therapy at the time of dismissal to prevent further episodes. Patients with a first-time episode of HE can be administered lactulose, and careful instructions should be provided to patients and caregivers about dose titration to achieve 3 bowel movements daily. Patients with recurrent HE episodes despite lactulose use benefit from the addition of rifaximin, which decreases the frequency of recurrent HE episodes and related hospitalizations. Last, patients and their families should be counseled about the risk of motor vehicle accidents, which require mandatory reporting to the Department of Motor Vehicles in some states.

    View details for DOI 10.1016/j.mayocp.2013.11.009

    View details for Web of Science ID 000330581500018

    View details for PubMedID 24411831

    View details for PubMedCentralID PMC4128786

  • Continuation of metformin use after a diagnosis of cirrhosis significantly improves survival of patients with diabetes. Hepatology (Baltimore, Md.) Zhang, X., Harmsen, W. S., Mettler, T. A., Kim, W. R., Roberts, R. O., Therneau, T. M., Roberts, L. R., Chaiteerakij, R. 2014


    The risks and benefits of metformin use in patients with cirrhosis with diabetes are debated. Although data on a protective effect of metformin against liver cancer development have been reported, metformin is frequently discontinued once cirrhosis is diagnosed because of concerns about an increased risk of adverse effects of metformin in patients with liver impairment. This study investigated whether continuation of metformin after cirrhosis diagnosis improves survival of patients with diabetes. Diabetic patients diagnosed with cirrhosis between 2000 and 2010 who were on metformin at the time of cirrhosis diagnosis were identified (n = 250). Data were retrospectively abstracted from the medical record. Survival of patients who continued versus discontinued metformin after cirrhosis diagnosis was compared using the log-rank test. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using Cox's proportional hazards analysis. Overall, 172 patients continued metformin whereas 78 discontinued metformin. Patients who continued metformin had a significantly longer median survival than those who discontinued metformin (11.8 vs. 5.6 years overall, P < 0.0001; 11.8 vs. 6.0 years for Child A patients, P = 0.006; and 7.7 vs. 3.5 years for Child B/C patients, P = 0.04, respectively). After adjusting for other variables, continuation of metformin remained an independent predictor of better survival, with an HR of 0.43 (95% CI: 0.24-0.78; P = 0.005). No patients developed metformin-associated lactic acidosis during follow-up. Conclusion: Continuation of metformin after cirrhosis diagnosis reduced the risk of death by 57%. Metformin should therefore be continued in diabetic patients with cirrhosis if there is no specific contraindication. (Hepatology 2014).

    View details for DOI 10.1002/hep.27199

    View details for PubMedID 24798175

    View details for PubMedCentralID PMC4218882

  • Efficacy and Safety of Treatment of Hepatitis C in Patients With Inflammatory Bowel Disease CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Allen, A. M., Kim, W. R., Larson, J., Loftus, E. V. 2013; 11 (12): 1655-U321


    There is uncertainty about the efficacy and safety of treatment for hepatitis C virus (HCV) infection in patients with inflammatory bowel disease (IBD). IBD can become exacerbated during treatment with interferon (IFN), and serious adverse events, such as pancytopenia or hepatotoxicity, can be compounded by drug interactions. We investigated the risk of exacerbation of IBD during HCV therapy and the rate of adverse effects of concomitant therapy for HCV and IBD. We also evaluated the efficacy of HCV treatment in the IBD population.We conducted a retrospective review of all patients who underwent IFN-based treatment for HCV at the Mayo Clinic in Rochester, Minnesota from 2001 to 2012. Exacerbation of IBD was evaluated by clinical, endoscopic, and histologic parameters during antiviral therapy and the ensuing 12 months. Hematologic toxicity was assessed by levels of all 3 cell lineages at baseline and during therapy. Efficacy of antiviral treatment was assessed by serum levels of HCV RNA until 24 weeks after completion of therapy. We also conducted a detailed MEDLINE database search and reviewed the literature on this topic.We identified 15 subjects with concomitant IBD (8 with ulcerative colitis and 7 with Crohn's disease). Only 1 patient experienced exacerbation of the disease during therapy; symptoms were controlled with mesalamine enemas. Another patient developed a flare shortly after completing antiviral therapy; symptoms returned spontaneously to baseline 2 weeks later. All subjects experienced an anticipated degree of pancytopenia while on IFN-based therapy. The rate of sustained virologic response was 67%. A concise review of available literature regarding the safety and efficacy of HCV treatment in IBD patients is also presented; although limited, the published data appear to support the safety of treatment with IFN in patients whose IBD is under control.In conjunction with data from the literature, our findings indicate that the efficacy and safety of HCV therapy with IFN and ribavirin for patients with IBD are comparable to those of subjects without IBD.

    View details for DOI 10.1016/j.cgh.2013.07.014

    View details for Web of Science ID 000327484800028

    View details for PubMedID 23891915

  • Risk Prediction of Hepatocellular Carcinoma in Patients with Cirrhosis: The ADRESS-HCC Risk Model 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases Flemming, J. A., Vittinghoff, E., Kim, W. R., Terrault, N. WILEY-BLACKWELL. 2013: 1219A–1220A
  • Impact of the center on graft failure after liver transplantation LIVER TRANSPLANTATION Asrani, S. K., Kim, W. R., Edwards, E. B., Larson, J. J., Thabut, G., Kremers, W. K., Therneau, T. M., Heimbach, J. 2013; 19 (9): 957-964


    The hospital at which liver transplantation (LT) is performed has a substantial impact on post-LT outcomes. Center-specific outcome data are closely monitored not only by the centers themselves but also by patients and government regulatory agencies. However, the true magnitude of this center effect, apart from the effects of the region and donor service area (DSA) as well as recipient and donor determinants of graft survival, has not been examined. We analyzed data submitted to the Organ Procurement and Transplantation Network for all adult (age ≥ 18 years) primary LT recipients (2005-2008). Using a mixed effects, proportional hazards regression analysis, we modeled graft failure within 1 year after LT on the basis of center (de-identified), region, DSA, and donor and recipient characteristics. At 115 unique centers, 14,654 recipients underwent transplantation. Rates of graft loss within a year varied from 5.9% for the lowest quartile of centers to 20.2% for the highest quartile. Gauged by a comparison of the 75th and 25th percentiles of the data, the magnitude of the center effect on graft survival (1.49-fold change) was similar to that of the recipient Model for End-Stage Liver Disease (MELD) score (1.47) and the donor risk index (DRI; 1.45). The center effect was similar across the DRI and MELD score quartiles and was not associated with a center's annual LT volume. After stratification by region and DSA, the magnitude of the center effect, though decreased, remained significant and substantial (1.30-fold interquartile difference). In conclusion, the LT center is a significant predictor of graft failure that is independent of region and DSA as well as donor and recipient characteristics.

    View details for DOI 10.1002/lt.23685

    View details for Web of Science ID 000323654800004

    View details for PubMedID 23784730

  • Advanced Fibrosis in Nonalcoholic Fatty Liver Disease: Noninvasive Assessment with MR Elastography RADIOLOGY Kim, D., Kim, W. R., Talwalkar, J. A., Kim, H. J., Ehman, R. L. 2013; 268 (2): 411-419


    To evaluate the diagnostic accuracy of magnetic resonance (MR) elastography as a method to help diagnose clinically substantial fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) and, by using MR elastography as a reference standard, to compare various laboratory marker panels in the identification of patients with NAFLD and advanced fibrosis.This retrospective study was institutional review board approved and HIPAA complaint. Informed consent was waived. This study was conducted in patients with NAFLD, who were identified by imaging characteristics consistent with steatosis in a prospective database that tracks all MR elastographic examinations. Six laboratory-based models of fibrosis were compared with MR elastographic results as well as fibrosis stage from liver biopsy results. The area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, positive predictive value, and negative predictive value of each data set were compared.Among 325 patients with NAFLD with MR elastographic data, there were 142 patients who underwent liver biopsy within 1 year of MR elastography. When comparing MR elastography results with liver biopsy results, the best cutoff for advanced fibrosis (stage F3-F4, 46 [32.4%] of 142) was 4.15 kPa (AUROC = 0.954, sensitivity = 0.85, specificity = 0.929). This cutoff value identified 104 patients with advanced fibrosis (32.0% of 325 patients). The FIB-4 score (AUROC = 0.827) and NAFLD fibrosis score (AUROC = 0.821) had the best diagnostic accuracy for advanced fibrosis, with high negative predictive values (NAFLD fibrosis score = 0.90 and FIB-4 score = 0.899).MR elastography is a useful diagnostic tool for detecting advanced fibrosis in NAFLD. Of the laboratory-based methods, the NAFLD fibrosis and FIB-4 scores can most reliably detect advanced fibrosis.

    View details for DOI 10.1148/radiol.13121193

    View details for Web of Science ID 000322116000015

    View details for PubMedID 23564711

  • Underestimation of Liver-Related Mortality in the United States GASTROENTEROLOGY Asrani, S. K., Larson, J. J., Yawn, B., Therneau, T. M., Kim, W. R. 2013; 145 (2): 375-?


    According to the National Center for Health Statistics (NCHS), chronic liver disease and cirrhosis is the 12(th) leading cause of death in the United States. However, this single descriptor might not adequately enumerate all deaths from liver disease. The aim of our study was to update data on liver mortality in the United States.Mortality data were obtained from the Rochester Epidemiology Project (1999-2008) and the National Death Registry (1979-2008). Liver-specific mortality values were calculated. In contrast to the narrow NCHS definition, updated liver-related causes of death included other specific liver diagnoses (eg, hepatorenal syndrome), viral hepatitis, and hepatobiliary cancers.The Rochester Epidemiology Project database contained information on 261 liver-related deaths, with an age- and sex-adjusted death rate of 27.0/100,000 persons (95% confidence interval: 23.7-30.3). Of these, only 71 deaths (27.2%) would have been captured by the NCHS definition. Of cases for which viral hepatitis or hepatobiliary cancer was the cause of death, 96.9% and 94.3% had liver-related immediate causes of death, respectively. In analysis of data from the National Death registry (2008), use of the updated definition increased liver mortality by >2-fold (from 11.7 to 25.7 deaths/100,000, respectively). Using NCHS definitions, liver-related deaths decreased from 18.9/100,000 in 1979 to 11.7/100,000 in 2008-a reduction of 38%. However, using the updated estimate, liver-related deaths were essentially unchanged from 1979 (25.8/100,000) to 2008 (25.7/100,000). Mortality burden was systematically underestimated among non-whites and persons of Hispanic ethnicity.Based on analyses of the Rochester Epidemiology Project and National Death databases, liver-related mortality has been underestimated during the past 2 decades in the United States.

    View details for DOI 10.1053/j.gastro.2013.04.005

    View details for Web of Science ID 000322630600027

    View details for PubMedID 23583430

  • Hepatitis B Screening and Vaccination Practices in Asian American Primary Care GUT AND LIVER Chu, D., Yang, J. D., Lok, A. S., Tram Tran, T., Martins, E. B., Fagan, E., Rousseau, F., Kim, W. R. 2013; 7 (4): 450-457


    Screening for hepatitis B virus (HBV) is recommended in populations with anticipated prevalence ≥2%. This study surveyed HBV screening and vaccination practices of Asian American primary care providers (PCPs).Approximately 15,000 PCPs with Asian surnames in the New York, Los Angeles, San Francisco, Houston, and Chicago areas were invited to participate in a web-based survey. Asian American PCPs with ≥25% Asian patients in their practice were eligible.Of 430 (2.9%) survey respondents, 217 completed the survey. Greater than 50% followed ≥200 Asian patients. Although 95% of PCPs claimed to have screened patients for HBV, 41% estimated that ≤25% of their adult Asian patients had ever been screened, and 50% did not routinely screen all Asian patients. In a multivariable analysis, the proportion of Asian patients in the practice, provider geographic origin and the number of liver cancers diagnosed in the preceding 12 months were significantly associated with a higher likelihood of screening for HBV. Over 80% of respondents reported that ≤50% of their adult Asian patients had received the HBV vaccine.Screening and vaccination for HBV in Asian American patients is inadequate. Measures to improve HBV knowledge and care by primary-care physicians are critically needed.

    View details for DOI 10.5009/gnl.2013.7.4.450

    View details for Web of Science ID 000322057500011

    View details for PubMedID 23898386

  • Excellent quality of life after liver transplantation for patients with perihilar cholangiocarcinoma who have undergone neoadjuvant chemoradiation LIVER TRANSPLANTATION Murad, S. D., Heimbach, J. K., Gores, G. J., Rosen, C. B., Benson, J. T., Kim, W. R. 2013; 19 (5): 521-528


    Patients with perihilar cholangiocarcinoma (CCA) undergoing neoadjuvant chemoradiation followed by liver transplantation (LT) have excellent survival. However, little is known about their quality of life (QOL). We assessed the QOL of these patients and compared it to the QOL of patients who underwent transplantation for other liver diseases. From 1993 to 2010, 129 CCA patients underwent LT, and 93 (72%) were alive as of November 2010. All recipients were sent a previously validated QOL questionnaire composed of disease-specific QOL metrics (liver disease symptoms, Karnofsky score, health perception, and index of well-being) and generic QOL metrics [Short Form 36 (SF-36) and European Quality of Life (EuroQol)]. These recipients were compared to 110 transplant recipients with other liver diseases (excluding hepatitis C). Among the recipients with CCA, the response rate was 85% (n = 79). Patients with CCA did significantly better on liver disease symptoms (3.3 versus 3.2, P = 0.05), the Karnofsky score (90.8 versus 86.6, P = 0.03), the SF-36 Physical Functioning domain (52.0 versus 46.3, P < 0.001), and the EuroQol Mobility category (10% versus 33%, P = 0.001), and they rated their overall health better in comparison with non-CCA patients (85.9 versus 80.7, P = 0.02). CCA patients scored consistently higher on all other domains, albeit without significant differences. The observed differences in QOL remained unchanged when adjustments were made for demographic factors, including the level of education. In conclusion, patients who underwent neoadjuvant chemoradiation followed by LT for perihilar CCA reported excellent QOL that was equal to or better than that of recipients with other liver diseases. These results are important in light of the continued debate about the feasibility of this aggressive treatment in patients with perihilar CCA.

    View details for DOI 10.1002/lt.23630

    View details for Web of Science ID 000318240400007

    View details for PubMedID 23447435

  • Association between noninvasive fibrosis markers and mortality among adults with nonalcoholic fatty liver disease in the United States HEPATOLOGY Kim, D., Kim, W. R., Kim, H. J., Therneau, T. M. 2013; 57 (4): 1357-1365


    The clinical and public health significance of nonalcoholic fatty liver disease (NAFLD) is not well established. We investigated the long-term effect of NAFLD on mortality. This analysis utilized the National Health and Nutrition Examination Survey conducted in 1988-1994 and subsequent follow-up data for mortality through December 31, 2006. NAFLD was defined by ultrasonographic detection of hepatic steatosis in the absence of other known liver diseases. The presence and severity of hepatic fibrosis in subjects with NAFLD was determined by the NAFLD fibrosis score (NFS), the aspartate aminotransferase to platelet ratio index (APRI), and FIB-4 score. Of 11,154 participants, 34.0% had NAFLD--the majority (71.7%) had NFS consistent with lack of significant fibrosis (NFS <-1.455), whereas 3.2% had a score indicative of advanced fibrosis (NFS >0.676). After a median follow-up of 14.5 years, NAFLD was not associated with higher mortality (age- and sex-adjusted hazard ratio [HR]: 1.05; 95% confidence interval [CI]: 0.93-1.19). In contrast, there was a progressive increase in mortality with advancing fibrosis scores. Compared to subjects without fibrosis, those with a high probability of advanced fibrosis had a 69% increase in mortality (for NFS: HR, 1.69, 95% CI: 1.09-2.63; for APRI: HR, 1.85, 95% CI: 1.02-3.37; for FIB-4: HR, 1.66, 95% CI: 0.98-2.82) after adjustment for other known predictors of mortality. These increases in mortality were almost entirely from cardiovascular causes (for NFS: HR, 3.46, 95% CI: 1.91-6.25; for APRI: HR, 2.53, 95% CI: 1.33-4.83; for FIB-4: HR, 2.68, 95% CI: 1.44-4.99).Ultrasonography-diagnosed NAFLD is not associated with increased mortality. However, advanced fibrosis, as determined by noninvasive fibrosis marker panels, is a significant predictor of mortality, mainly from cardiovascular causes, independent of other known factors.

    View details for DOI 10.1002/hep.26156

    View details for Web of Science ID 000317363600010

    View details for PubMedID 23175136

  • Predicting clinical outcomes with elastography in primary biliary cirrhosis: one step closer? Gastroenterology Singh, S., Kim, W. R., Talwalkar, J. A. 2013; 144 (4): 851-852

    View details for DOI 10.1053/j.gastro.2013.02.024

    View details for PubMedID 23462134

  • Risk Factors for Intrahepatic Cholangiocarcinoma: Association Between Metformin Use and Reduced Cancer Risk HEPATOLOGY Chaiteerakij, R., Yang, J. D., Harmsen, W. S., Slettedahl, S. W., Mettler, T. A., Fredericksen, Z. S., Kim, W. R., Gores, G. J., Roberts, R. O., Olson, J. E., Therneau, T. M., Roberts, L. R. 2013; 57 (2): 648-655


    The associations between diabetes, smoking, obesity, and intrahepatic cholangiocarcinoma (ICC) risk remain inconclusive. Metformin is purportedly associated with a reduced risk for various cancers. This case-control study evaluated risk factors for ICC and explored the effects of metformin on ICC risk in a clinic/hospital-based cohort. ICC patients observed at the Mayo Clinic (Rochester, MN) between January 2000 and May 2010 were identified. Age, sex, ethnicity, and residential area-matched controls were selected from among Mayo Clinic Biobank participants. The associations between potential factors and ICC risk were determined. Six hundred and twelve cases and 594 controls were identified. Factors associated with increased ICC risk included biliary tract diseases (adjusted odds ratio [AOR]: 81.8; 95% confidence interval [CI]: 11.2-598.8; P < 0.001), cirrhosis (AOR, 8.0; 95% CI: 1.8-36.5; P = 0.007), diabetes (AOR, 3.6; 95% CI: 2.3-5.5; P < 0.001), and smoking (AOR, 1.6; 95% CI: 1.3-2.1; P < 0.001). Compared to diabetic patients not treated with metformin, the odds ratio (OR) for ICC for diabetic patients treated with metformin was significantly decreased (OR, 0.4; 95% CI: 0.2-0.9; P = 0.04). Obesity and metabolic syndrome were not associated with ICC.This study confirmed diabetes and smoking as independent risk factors for ICC. A novel finding was that treatment with metformin was significantly associated with a 60% reduction in ICC risk in diabetic patients.

    View details for DOI 10.1002/hep.26092

    View details for Web of Science ID 000315643400024

    View details for PubMedID 23055147

  • Assessing the cost utility of response-guided therapy in patients with chronic hepatitis C genotype 1 in the UK using the MONARCH model. Applied health economics and health policy McEwan, P., Kim, R., Yuan, Y. 2013; 11 (1): 53-63


    European guidelines advocate the measurement of on-treatment hepatitis C virus (HCV) RNA in order to determine optimal therapy duration (response-guided therapy [RGT]) in patients with rapid virological response (RVR) or delayed virological response (DVR). Treatment response is highly dependent upon the extent of liver fibrosis yet there is little evidence quantifying the cost effectiveness of RGT particularly conditional upon fibrosis stage.This study describes an economic model designed to assess the costs and benefits of RGT compared with standard duration of therapy (SDT) in hepatitis C virus genotype 1 patients.A Markov cohort simulation model with lifetime perspective was developed to undertake a cost utility analysis of RGT in the UK. Patients entered the model at Metavir disease stages F0-F4, and progressed through these stages via age and duration of HCV infection-dependent transition probabilities. Treated patients were partitioned according to virological response and shortened or extended duration of therapy was applied following European guidelines.For all patients, SDT and RGT was associated with an increase of 2.14 and 2.20 QALYs and £2,374 and £2,270 costs, respectively, compared with no treatment. Overall, RGT was a dominant scenario being associated with a lower risk of complications, increased QALYs (0.08) and cost saving (£101). RGT across fibrosis stages was either highly cost effective or dominant; in all cases RGT was associated with an increase in QALYs, driven by a reduction in complications in DVR subjects and reduced exposure to treatment disutility in RVR subjects; costs were lower in F1 and F2 fibrosis stages. At a willingness-to-pay threshold of £20,000 per QALY, overall RGT across fibrosis stages F2-F4 were associated with the highest probability of being cost effective. At this threshold, the probability of reduced/extended therapy in RVR/DVR patients being cost effective is 0.35 and 0.88, respectively.This analysis suggests that the treatment of HCV genotype 1 patients in fibrosis stage F2 has the greatest potential for maximizing health benefit and cost saving within an RGT protocol. Predicting those patients most likely to respond to treatments is important from both a clinical and cost perspective and the tailoring of treatment duration with the current standard of care is likely to remain a priority for payers with budgetary constraints.

    View details for DOI 10.1007/s40258-012-0002-0

    View details for PubMedID 23329380

  • Kidney, Pancreas and Liver Allocation and Distribution in the United States AMERICAN JOURNAL OF TRANSPLANTATION Smith, J. M., Biggins, S. W., Haselby, D. G., Kim, W. R., Wedd, J., Lamb, K., Thompson, B., Segev, D. L., Gustafson, S., Kandaswamy, R., Stock, P. G., Matas, A. J., Samana, C. J., Sleeman, E. F., Stewart, D., Harper, A., Edwards, E., Snyder, J. J., Kasiske, B. L., Israni, A. K. 2012; 12 (12): 3191-3212


    Kidney transplant and liver transplant are the treatments of choice for patients with end-stage renal disease and end-stage liver disease, respectively. Pancreas transplant is most commonly performed along with kidney transplant in diabetic end-stage renal disease patients. Despite a steady increase in the numbers of kidney and liver transplants performed each year in the United States, a significant shortage of kidneys and livers available for transplant remains. Organ allocation is the process the Organ Procurement and Transplantation Network (OPTN) uses to determine which candidates are offered which deceased donor organs. OPTN is charged with ensuring the effectiveness, efficiency and equity of organ sharing in the national system of organ allocation. The policy has changed incrementally over time in efforts to optimize allocation to meet these often competing goals. This review describes the history, current status and future direction of policies regarding the allocation of abdominal organs for transplant, namely the kidney, liver and pancreas, in the United States.

    View details for DOI 10.1111/j.1600-6143.2012.04259.x

    View details for Web of Science ID 000311854800007

    View details for PubMedID 23157207

  • Simultaneous Liver-Kidney Transplantation Summit: Current State and Future Directions AMERICAN JOURNAL OF TRANSPLANTATION Nadim, M. K., Sung, R. S., Davis, C. L., Andreoni, K. A., Biggins, S. W., Danovitch, G. M., Feng, S., Friedewald, J. J., Hong, J. C., Kellum, J. A., Kim, W. R., Lake, J. R., Melton, L. B., Pomfret, E. A., Saab, S., Genyk, Y. S. 2012; 12 (11): 2901-2908


    Although previous consensus recommendations have helped define patients who would benefit from simultaneous liver-kidney transplantation (SLK), there is a current need to reassess published guidelines for SLK because of continuing increase in proportion of liver transplant candidates with renal dysfunction and ongoing donor organ shortage. The purpose of this consensus meeting was to critically evaluate published and registry data regarding patient and renal outcomes following liver transplantation alone or SLK in liver transplant recipients with renal dysfunction. Modifications to the current guidelines for SLK and a research agenda were proposed.

    View details for DOI 10.1111/j.1600-6143.2012.04190.x

    View details for Web of Science ID 000310478600008

    View details for PubMedID 22822723

  • Predictors of pretransplant dropout and posttransplant recurrence in patients with perihilar cholangiocarcinoma HEPATOLOGY Murad, S. D., Kim, W. R., Therneau, T., Gores, G. J., Rosen, C. B., Martenson, J. A., Alberts, S. R., Heimbach, J. K. 2012; 56 (3): 972-981


    We have previously reported excellent outcomes with liver transplantation for selected patients with early-stage perihilar cholangiocarcinoma (CCA) following neoadjuvant chemoradiotherapy. Our aim was to identify predictors of dropout before transplantation and predictors of cancer recurrence after transplantation. We reviewed all patients with unresectable perihilar CCA treated with neoadjuvant chemoradiation in anticipation for transplantation between 1993 and 2010. Predictors were identified by univariate and multivariate Cox regression analysis of clinical variables. In total, 199 patients were enrolled, of whom 62 dropped out and 131 underwent transplantation at our institution, with six undergoing transplantation elsewhere. Predictors of dropout were carbohydrate antigen 19-9 (CA 19-9) ≥ 500 U/mL (hazard ratio [HR] 2.3; P = 0.04), mass ≥ 3 cm (HR 2.1; P = 0.05), malignant brushing or biopsy (HR 3.6; P = 0.001), and Model for End-Stage Liver Disease (MELD) score ≥ 20 (HR 3.5; P = 0.02). Posttransplant, recurrence-free 5-year survival was 68%. Predictors of recurrence were elevated CA 19-9 (HR 1.8; P = 0.01), portal vein encasement (HR 3.3; P = 0.007), and residual tumor on explant (HR 9.8; P < 0.001). Primary sclerosing cholangitis (PSC), age, history of cholecystectomy, and waiting time were not independent predictors.Outcome following neoadjuvant chemoradiation and liver transplantation for perihilar CCA is excellent. Risk of dropout is related to patient and tumor characteristics and this can be used to guide patient counseling before enrollment. Recurrence risk is mostly associated with presence of residual cancer on explant. Patients with PSC do not have an independent survival advantage over de novo patients, but present with more favorable tumor characteristics.

    View details for DOI 10.1002/hep.25629

    View details for Web of Science ID 000308046700021

    View details for PubMedID 22290335

  • Biliary Tract Cancers in Olmsted County, Minnesota, 1976-2008 AMERICAN JOURNAL OF GASTROENTEROLOGY Yang, J. D., Kim, B., Sanderson, S. O., St Sauver, J., Yawn, B. P., Larson, J. J., Therneau, T. M., Roberts, L. R., Gores, G. J., Kim, W. R. 2012; 107 (8): 1256-1262


    The epidemiology of biliary tract cancers has changed in the United States in the past several decades. The aim of this study is to evaluate biliary tract cancers with regard to the incidence rates, etiology, treatment, and survival in Olmsted County between 1976 and 2008.Community residents over 20 years of age with a newly diagnosed biliary tract cancers were identified using the Rochester Epidemiology Project. Clinical information, including tumor stage, treatment, and survival status was abstracted from the medical records. The incidence rate was calculated considering the entire population of Olmsted County to be at risk and adjusted by age and sex according to US Census 2000 population. Temporal trends of patient survival with biliary tract cancers were assessed.A total of 116 subjects met the study criteria. The age-sex-adjusted incidence rate of intrahepatic cholangiocarcinoma (ICC) increased from 0.3 to 2.1 (P=0.02) but one of gall bladder (GB) cancer decreased from 4.0 to 2.2 (P=0.04) per 100,000 person-years between 1976 and 2008 (P<0.01). Overall incidence rates of remaining biliary tract cancers have not changed. Overall 59% of patients presented with stage 3 or 4 cancers and a median survival was 6.3 months. Survival in patients with biliary tract cancer has minimally improved from median survival of 4.2-7.7 months between 1976 and 2008 (P=0.05).In Olmsted County, the incidence of ICC and GB cancer has increased and decreased, respectively. The prognosis remains poor in community residents diagnosed with biliary tract cancers.

    View details for DOI 10.1038/ajg.2012.173

    View details for Web of Science ID 000308061800018

    View details for PubMedID 22751468

  • Model to estimate survival in ambulatory patients with hepatocellular carcinoma HEPATOLOGY Yang, J. D., Kim, W. R., Park, K. W., Chaiteerakij, R., Kim, B., Sanderson, S. O., Larson, J. J., Pedersen, R. A., Therneau, T. M., Gores, G. J., Roberts, L. R., Park, J. 2012; 56 (2): 614-621


    Survival of patients with hepatocellular carcinoma (HCC) is determined by the extent of the tumor and the underlying liver function. We aimed to develop a survival model for HCC based on objective parameters including the Model for Endstage Liver Disease (MELD) as a gauge of liver dysfunction. This analysis is based on 477 patients with HCC seen at Mayo Clinic Rochester between 1994 and 2008 (derivation cohort) and 904 patients at the Korean National Cancer Center between 2000 and 2003 (validation cohort). Multivariate proportional hazards models and corresponding risk score were created based on baseline demographic, clinical, and tumor characteristics. Internal and external validation of the model was performed. Discrimination and calibration of this new model were compared against existing models including Barcelona Clinic Liver Cancer (BCLC), Cancer of the Liver Italian Program (CLIP), and Japan Integrated Staging (JIS) scores. The majority of the patients had viral hepatitis as the underlying liver disease (100% in the derivation cohort and 85% in the validation cohort). The survival model incorporated MELD, age, number of tumor nodules, size of the largest nodule, vascular invasion, metastasis, serum albumin, and alpha-fetoprotein. In cross-validation, the coefficients remained largely unchanged between iterations. Observed survival in the validation cohort matched closely with what was predicted by the model. The concordance (c)-statistic for this model (0.77) was superior to that for BCLC (0.71), CLIP (0.70), or JIS (0.70). The score was able to further classify patient survival within each stage of the BCLC classification.A new model to predict survival of HCC patients based on objective parameters provides refined prognostication and supplements the BCLC classification.

    View details for DOI 10.1002/hep.25680

    View details for Web of Science ID 000306804500025

    View details for PubMedID 22370914

  • Nonalcoholic fatty liver disease is associated with coronary artery calcification HEPATOLOGY Kim, D., Choi, S., Park, E. H., Lee, W., Kang, J. H., Kim, W., Kim, Y. J., Yoon, J., Jeong, S. H., Lee, D. H., Lee, H., Larson, J., Therneau, T. M., Kim, W. R. 2012; 56 (2): 605-613


    Nonalcoholic fatty liver disease (NAFLD) is related to risk factors of coronary artery disease, such as dyslipidemia, diabetes, and metabolic syndrome, which are closely linked with visceral adiposity. The aim of this study was to investigate whether NAFLD was associated with coronary artery calcification (CAC), which is used as a surrogate marker for coronary atherosclerosis independent of computed tomography (CT)-measured visceral adiposity. Out of 5,648 subjects who visited one of our health screening centers between 2003 and 2008, we enrolled 4,023 subjects (mean age, 56.9 ± 9.4 years; 60.7% males) without known liver disease or a history of ischemic heart disease. CAC score was evaluated using the Agatston method. On univariate analysis, the presence of CAC (score >0) was significantly associated with age, sex, body mass index, aspartate aminotransferase, alanine aminotransferase, high-density lipoprotein cholesterol, triglycerides, and increased risk of diabetes, hypertension, smoking, and NAFLD. Increasing CAC scores (0, <10, 10-100, ≥ 100) were associated with higher prevalence of NAFLD (odds ratio [OR], 1.84; 95% confidence interval [CI], 1.61-2.10; P<0.001). Multivariable ordinal regression analysis was adjusted for traditional risk factors, and CT-measured visceral adipose tissue area in a subgroup of subjects showed that the increased CAC scores were significantly associated with the presence of NAFLD (OR, 1.28, 95% CI, 1.04-1.59; P = 0.023) independent of visceral adiposity.Patients with NAFLD are at increased risk for coronary atherosclerosis independent of classical coronary risk factors, including visceral adiposity. These data suggest that NAFLD might be an independent risk factor for coronary artery disease.

    View details for DOI 10.1002/hep.25593

    View details for Web of Science ID 000306804500024

    View details for PubMedID 22271511

  • Efficacy of neoadjuvant chemoradiation, followed by liver transplantation, for perihilar cholangiocarcinoma at 12 US centers. Gastroenterology Darwish Murad, S., Kim, W. R., Harnois, D. M., Douglas, D. D., Burton, J., Kulik, L. M., Botha, J. F., Mezrich, J. D., Chapman, W. C., Schwartz, J. J., Hong, J. C., Emond, J. C., Jeon, H., Rosen, C. B., Gores, G. J., Heimbach, J. K. 2012; 143 (1): 88-98 e3


    Excellent single-center outcomes of neoadjuvant chemoradiation and liver transplantation for unresectable perihilar cholangiocarcinoma caused the United Network of Organ Sharing to offer a standardized model of end-stage liver disease (MELD) exception for this disease. We analyzed data from multiple centers to determine the effectiveness of this treatment and the appropriateness of the MELD exception.We collected and analyzed data from 12 large-volume transplant centers in the United States. These centers met the inclusion criteria of treating 3 or more patients with perihilar cholangiocarcinoma using neoadjuvant therapy, followed by liver transplantation, from 1993 to 2010 (n = 287 total patients). Center-specific protocols and medical charts were reviewed on-site.The patients completed external radiation (99%), brachytherapy (75%), radiosensitizing therapy (98%), and/or maintenance chemotherapy (65%). Seventy-one patients dropped out before liver transplantation (rate, 11.5% in 3 months). Intent-to-treat survival rates were 68% and 53%, 2 and 5 years after therapy, respectively; post-transplant, recurrence-free survival rates were 78% and 65%, respectively. Patients outside the United Network of Organ Sharing criteria (those with tumor mass >3 cm, transperitoneal tumor biopsy, or metastatic disease) or with a prior malignancy had significantly shorter survival times (P < .001). There were no differences in outcomes among patients based on differences in surgical staging or brachytherapy. Although most patients came from 1 center (n = 193), the other 11 centers had similar survival times after therapy.Patients with perihilar cholangiocarcinoma who were treated with neoadjuvant therapy followed up by liver transplantation at 12 US centers had a 65% rate of recurrence-free survival after 5 years, showing this therapy to be highly effective. An 11.5% drop-out rate after 3.5 months of therapy indicates the appropriateness of the MELD exception. Rigorous selection is important for the continued success of this treatment.

    View details for DOI 10.1053/j.gastro.2012.04.008

    View details for PubMedID 22504095

  • Efficacy of Neoadjuvant Chemoradiation, Followed by Liver Transplantation, for Perihilar Cholangiocarcinoma at 12 US Centers GASTROENTEROLOGY Murad, S. D., Kim, W. R., Harnois, D. M., Douglas, D. D., Burton, J., Kulik, L. M., Botha, J. F., Mezrich, J. D., Chapman, W. C., Schwartz, J. J., Hong, J. C., Emond, J. C., Jeon, H., Rosen, C. B., Gores, G. J., Heimbach, J. K. 2012; 143 (1): 88-U610
  • Hospitalization for Underage Drinkers in the United States JOURNAL OF ADOLESCENT HEALTH Kim, J. Y., Asrani, S. K., Shah, N. D., Kim, W. R., Schneekloth, T. D. 2012; 50 (6): 648-650


    Underage drinking is common in the United States. This article presents nationally representative data on hospitalizations for alcohol use disorder (AUD) in youth.Using the Nationwide Inpatient Sample database, discharge records of individuals between 15 and 20 years diagnosed with AUD were identified. Incidence rates of these hospitalizations were calculated based on population estimates from the US Census Bureau.In 2008, there were 699,506 nonobstetric discharges in 15- to 20-year-olds, of which 39,619 (5.6%) had an AUD diagnosis with or without an injury diagnosis. The overall annual incidence of AUD hospitalization was 18.3 per 10,000 boys and 12.3 per 10,000 girls. Native American boys in the Midwest had the highest incidence (101 per 10,000), and Asian/Pacific Islander girls in the South had the lowest (2 per 10,000). The estimated total charges for these hospitalizations were $755 million in 2008.Hospitalization care for underage drinking is common, especially in certain race and in certain geographic regions and is associated with a substantial health care expenditure.

    View details for DOI 10.1016/j.jadohealth.2011.10.250

    View details for Web of Science ID 000304668600019

    View details for PubMedID 22626495

  • Development of organ-specific donor risk indices LIVER TRANSPLANTATION Akkina, S. K., Asrani, S. K., Peng, Y., Stock, P., Kim, W. R., Israni, A. K. 2012; 18 (4): 395-404


    Because of the shortage of deceased donor organs, transplant centers accept organs from marginal deceased donors, including older donors. Organ-specific donor risk indices have been developed to predict graft survival with various combinations of donor and recipient characteristics. Here we review the kidney donor risk index (KDRI) and the liver donor risk index (LDRI) and compare and contrast their strengths, limitations, and potential uses. The KDRI has a potential role in developing new kidney allocation algorithms. The LDRI allows a greater appreciation of the importance of donor factors, particularly for hepatitis C virus-positive recipients; as the donor risk index increases, the rates of allograft and patient survival among these recipients decrease disproportionately. The use of livers with high donor risk indices is associated with increased hospital costs that are independent of recipient risk factors, and the transplantation of livers with high donor risk indices into patients with Model for End-Stage Liver Disease scores < 15 is associated with lower allograft survival; the use of the LDRI has limited this practice. Significant regional variations in donor quality, as measured by the LDRI, remain in the United States. We also review other potential indices for liver transplantation, including donor-recipient matching and the retransplant donor risk index. Although substantial progress has been made in developing donor risk indices to objectively assess donor variables that affect transplant outcomes, continued efforts are warranted to improve these indices to enhance organ allocation policies and optimize allograft survival.

    View details for DOI 10.1002/lt.23398

    View details for Web of Science ID 000302148400006

    View details for PubMedID 22287036

  • Surveillance for Hepatocellular Carcinoma in Patients With Cirrhosis CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Yang, J. D., Kim, W. R. 2012; 10 (1): 16-21

    View details for DOI 10.1016/j.cgh.2011.06.004

    View details for Web of Science ID 000298812400011

    View details for PubMedID 21699816

  • Hepatocellular Carcinoma in Olmsted County, Minnesota, 1976-2008 MAYO CLINIC PROCEEDINGS Yang, J. D., Kim, B., Sanderson, S. O., St Sauver, J. L., Yawn, B. P., Pedersen, R. A., Larson, J. J., Therneau, T. M., Roberts, L. R., Kim, W. R. 2012; 87 (1): 9-16


    To analyze longitudinal trends in the incidence, etiology, and treatment of hepatocellular carcinoma (HCC) in community residents in Olmsted County, Minnesota, and their survival.Olmsted County residents 20 years or older with HCC newly diagnosed from January 1, 1976, through December 31, 2008, were identified using a community-wide medical record linkage system (Rochester Epidemiology Project). The incidence rate of HCC was calculated by age and sex according to the 2000 US Census population. Temporal trends of HCC etiology, treatment, and patient survival were assessed.The age- and sex-adjusted incidence rate for HCC in Olmsted County was 3.5 per 100,000 person-years for the first era (1976-1990), 3.8 per 100,000 for the second era (1991-2000), and 6.9 per 100,000 for the third era (2001-2008). Alcohol use was the most common risk factor in the first and second eras and chronic hepatitis C virus in the third. The proportion attributed to nonalcoholic fatty liver disease was small (5/47 [10.6%] in the third era). Because the proportion of patients receiving curative treatment increased over time, survival also improved, with a median survival time of 3, 6, and 9 months in the first, second, and third eras, respectively (P=.01).In this midwestern US community, the incidence of HCC has increased, primarily due to hepatitis C virus. Although there was a demonstrable improvement in the outcome of HCC in community residents over time, the overall prognosis remains poor.

    View details for DOI 10.1016/j.mayocp.2011.07.001

    View details for Web of Science ID 000299667300003

    View details for PubMedID 22212963

    View details for PubMedCentralID PMC3538386

  • Nonalcoholic fatty liver disease associated with coronary artery calcification Hepatology Kim, D., Choi, S., Park, E., Lee, W., Kang, J., Kim, W., Kim, Y., Yoon, J., Jeong, S., Lee, D., Lee, H., Larson, J., Therneau, T., Kim, W. 2012; 56 (2): 605-613
  • Factors That Affect Risk for Hepatocellular Carcinoma and Effects of Surveillance CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Yang, J. D., Harmsen, W. S., Slettedahl, S. W., Chaiteerakij, R., Enders, F. T., Therneau, T. M., Orsini, L., Kim, W. R., Roberts, L. R. 2011; 9 (7): 617-U141


    The incidence of hepatocellular carcinoma (HCC) in the United States is increasing. Surveillance may affect the stage at diagnosis and consequently the treatment options available for HCC. We evaluated risk factors for HCC, the proportion of cases detected via surveillance, tumor characteristics, treatment approaches, and overall patient survival in a referral center cohort.The study included all patients diagnosed with HCC at the Mayo Clinic, Rochester, Minnesota, from 2007 to 2009 (n = 460). Clinical information was retrospectively abstracted from the medical record.Hepatitis C virus (HCV, 36%), alcohol use (29%), and nonalcoholic fatty liver disease (NAFLD, 13%) were the most common risk factors for HCC. HCV was present in 56% of patients younger than 60. NAFLD was present in 19% of patients older than 60. HCC was detected during surveillance in 31% of patients. Patients with worse liver function were more likely to be on surveillance. Transarterial chemoembolization, surgical resection, and liver transplantation were the most common treatment approaches for HCC. Patients diagnosed with HCC during surveillance had less advanced disease, were more likely to be eligible for potentially curative treatments, and had increased survival times (P < .001).At a major US referral center, the predominant HCC etiologies were HCV, alcohol use, and NAFLD. HCCs were detected during surveillance in the minority of patients. HCCs detected during surveillance were of less advanced stage, and patients were more likely to receive treatment that prolonged their survival.

    View details for DOI 10.1016/j.cgh.2011.03.027

    View details for Web of Science ID 000292467900023

    View details for PubMedID 21459158

  • A Revised Model for End-Stage Liver Disease Optimizes Prediction of Mortality Among Patients Awaiting Liver Transplantation GASTROENTEROLOGY Leise, M. D., Kim, W. R., Kremers, W. K., Larson, J. J., Benson, J. T., Therneau, T. M. 2011; 140 (7): 1952-1960


    The Model for End Stage Liver Disease (MELD) was originally developed based on data from patients who underwent the transjugular intrahepatic portosystemic shunt procedure. An updated MELD based on data from patients awaiting liver transplantation should improve mortality prediction and allocation efficiency.Wait-list data from adult primary liver transplantation candidates from the Organ Procurement and Transplantation Network were divided into a model derivation set (2005-2006; n=14,214) and validation set (2007-2008; n=13,945). Cox regression analysis was used to derive and validate an optimized model that updated coefficients and upper and lower bounds for MELD components and included serum levels of sodium. Main outcomes measure was ability to predict 90-day mortality of patients on the liver transplantation wait list.Optimized MELD score updated coefficients and implemented new upper and lower bounds for creatinine (0.8 and 3.0 mg/dL, respectively) and international normalized ratio (1 and 3, respectively). Serum sodium concentrations significantly predicted mortality, even after adjusting for the updated MELD model. The final model, based on updated fit of the 4 variables (ie, bilirubin, creatinine, international normalized ratio, and sodium) had a modest yet statistically significant gain in discrimination (concordance: 0.878 vs 0.865; P<.01) in the validation dataset. Utilization of the new score could affect up to 12% of patients (based on changed score for 459 of 3981 transplants in the validation set).Modification of MELD score to update coefficients, change upper and lower bounds, and incorporate serum sodium levels improved wait-list mortality prediction and should increase efficiency of allocation of donated livers.

    View details for DOI 10.1053/j.gastro.2011.02.017

    View details for Web of Science ID 000291388200029

    View details for PubMedID 21334338

  • Born to be wild or just confused? Genetic predisposition to hepatic encephalopathy. Gastroenterology Duarte-Rojo, A., Kamath, P. S., Kim, W. R. 2011; 140 (7): 2137-2138

    View details for DOI 10.1053/j.gastro.2011.04.018

    View details for PubMedID 21521639

  • Many Patients With Primary Sclerosing Cholangitis and Increased Serum Levels of Carbohydrate Antigen 19-9 Do Not Have Cholangiocarcinoma CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Sinakos, E., Saenger, A. K., Keach, J., Kim, W. R., Lindor, K. D. 2011; 9 (5): 434-U1433


    Patients with primary sclerosing cholangitis (PSC) have an increased incidence of cholangiocarcinoma (CCA). Carbohydrate antigen 19-9 (CA 19-9) is the main serum marker used to diagnose CCA, although increased levels of CA 19-9 are also associated with other hepatic complications. We evaluated the long-term outcomes in patients with PSC and significant increases in levels of CA 19-9.We analyzed data from all Mayo Clinic patients with PSC and serum levels of CA 19-9 greater than 129 U/mL from 2000-2010 (n = 73). We reviewed patients' records for CCA diagnosis, other malignancies, recurrent bacterial cholangitis, and persistent cholestasis.Thirty-seven percent of patients reviewed had no evidence of CCA after a median follow-up time of 30 months. The initial levels of CA 19-9 from patients without CCA were significantly lower than those from patients with CCA (286 vs 895 U/mL, P < .0001). At the start of the study, patients without CCA were more likely to have cirrhosis, compared with patients with CCA (48% vs 24%, P = .03), and lower levels of bilirubin (2 vs 6.8 mg/dL, P = .003), compared with patients with CCA. No factors known to affect CA 19-9 levels were identified in 33% of patients without CCA; endoscopic treatment and recurrent bacterial cholangitis were associated with levels of CA 19-9 in 26% and 22% of these patients, respectively.Thirty-seven percent of patients with PSC who have serum levels of CA 19-9 greater than 129 U/mL do not have CCA. Additional studies should be performed to determine the outcomes of these patients.

    View details for DOI 10.1016/j.cgh.2011.02.007

    View details for Web of Science ID 000290657200020

    View details for PubMedID 21334457

  • Cirrhosis Is Present in Most Patients With Hepatitis B and Hepatocellular Carcinoma CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Yang, J. D., Kim, W. R., Coelho, R., Mettler, T. A., Benson, J. T., Sanderson, S. O., Therneau, T. M., Kim, B., Roberts, L. R. 2011; 9 (1): 64-70


    There are few data available about the prevalence or effects of cirrhosis in patients with hepatocellular carcinoma (HCC) from viral hepatitis. We compared patients with HCC and hepatitis B virus (HBV) or hepatitis C virus (HCV) infections to determine the proportions of cirrhosis in each group, virologic and tumor characteristics, and overall survival.This analysis included patients with HBV (n = 64) or HCV (n = 118) infection who were diagnosed with HCC at the Mayo Clinic in Rochester, Minnesota from 1994-2008; groups were matched for age and sex. The diagnosis of cirrhosis was based on histology and, if histologic information was insufficient or unavailable, clinical indicators that included ascites or varices, thrombocytopenia or splenomegaly, and radiographic configuration of cirrhosis. Virologic characteristics, tumor stage, and patient survival were also assessed.The prevalence of histologic cirrhosis was 88% among patients with HBV infection and 93% among those with HCV infection (P = .46). When the most inclusive criteria for cirrhosis were applied, cirrhosis was present in 94% of patients with HBV and 97% with HCV (P = .24). Among HCV patients, 5.2% were negative for HCV RNA after antiviral treatment; 63.4% of HBV patients had HBV DNA <2000 IU/mL with or without treatment. Patients with HBV tended to have less surveillance and more advanced stages of HCC, without differences in survival from those with HCV infection (P = .75).Most patients with HCC and chronic viral hepatitis had evidence of cirrhosis, including those with HBV infection and those without active viral replication.

    View details for DOI 10.1016/j.cgh.2010.08.019

    View details for Web of Science ID 000285980600019

    View details for PubMedID 20831903

  • The impact of hepatitis C on labor force participation, absenteeism, presenteeism and non-work activities. Journal of medical economics DiBonaventura, M. D., Wagner, J., Yuan, Y., L'Italien, G., Langley, P., Ray Kim, W. 2011; 14 (2): 253-261


    Between 2.7 and 3.9 million people are currently infected with the hepatitis C virus (HCV) in the United States. Although many studies have investigated the impact of HCV on direct healthcare costs, few studies have estimated the indirect costs associated with the virus using a nationally-representative dataset.Using data from the 2009 United States (US) National Health and Wellness Survey, patients who reported a hepatitis C diagnosis (n = 695) were compared to controls on labor force participation, productivity loss, and activity impairment after adjusting for demographics, health risk behaviors, and comorbidities. All analyses applied sampling weights to project to the population.Patients with HCV were significantly less likely to be in the labor force than controls and reported significantly higher levels of absenteeism (4.88 vs. 3.03%), presenteeism (16.69 vs. 13.50%), overall work impairment (19.40 vs.15.35%), and activity impairment (25.01 vs. 21.78%). A propensity score matching methodology replicated many of these findings.While much of the work on HCV has focused on direct costs, our results suggest indirect costs should not be ignored when quantifying the societal burden of HCV. To our knowledge, this is the first study which has utilized a large, nationally-representative data source for identifying the impact of HCV on labor force participation and work and activity impairment using both a propensity-score matching and a regression modeling framework.All data were patient-reported (including HCV diagnosis and work productivity), which could have introduced some subjective biases.

    View details for DOI 10.3111/13696998.2011.566294

    View details for PubMedID 21385147

  • Utility of Serum YKL-40 as a Tumor-Specific Marker of Hepatobiliary Malignancies GUT AND LIVER Yang, J. D., Kim, E., Pedersen, R. A., Kim, W. R., Pungpapong, S., Roberts, L. R. 2010; 4 (4): 537-542


    Serum YKL-40 has been linked to several human cancers. We investigated the potential role of serum YKL-40 as a marker of hepatobiliary malignancies.Archived serum samples of patients undergoing liver transplantation evaluation at the Mayo Clinic Rochester were used to measure YKL-40 levels. Patients were divided into three groups: hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and end-stage liver disease (ESLD) without malignancies. The Model for ESLD (MELD) score was used to quantify the severity of liver disease.The median serum YKL-40 level was highest in the ESLD group at 296 ng/mL, compared to 259 ng/mL in the HCC group and 80 ng/mL in the CCA group (p<0.01). There was a significant correlation between the MELD score and serum YKL-40 level (r=0.50, p<0.01). In a multivariate analysis, there was no significant difference in serum YKL-40 level between ESLD and HCC. CCA was associated with lower YKL-40 levels, a finding that was attributable to a lower prevalence of cirrhosis.The serum YKL-40 level has little utility as a cross-sectional screening tool for hepatobiliary malignancies, namely HCC and CCA. The role of YKL-40 as a surveillance marker in the follow-up of individual patients remains to be determined.

    View details for DOI 10.5009/gnl.2010.4.4.537

    View details for Web of Science ID 000285445100014

    View details for PubMedID 21253305

  • Endothelial Nitric Oxide Synthase Gene Variation Associated With Chronic Kidney Disease After Liver Transplant MAYO CLINIC PROCEEDINGS Bambha, K., Kim, W. R., Rosen, C. B., Pedersen, R. A., Rys, C., Kolbert, C. P., Cunningham, J. M., Therneau, T. M. 2010; 85 (9): 814-820


    To identify single nucleotide polymorphisms (SNPs) associated with risk of developing chronic kidney disease (CKD), a prevalent comorbidity, after liver transplant (LT).This study consists of a cohort of adult (> or =18 years) primary-LT recipients who had normal renal function before LT and who survived 1 year or more after LT at a high-volume US LT program between January 1, 1990, and December 31, 2000. Patients with adequate renal function (estimated glomerular filtration rate, > or =40 mL/min per 1.73 m(2) during follow-up; n=308) and patients with incident CKD (estimated glomerular filtration rate, <40 mL/min per 1.73 m(2) after LT; n=92) were identified. To investigate the association of 6 candidate genes with post-LT CKD, we selected SNPs that have been associated with renal function in the literature. Hazard ratios were estimated using Cox regression, adjusted for potential confounding variables.The variant allele (298Asp) of the Glu298Asp SNP in the endothelial nitric oxide synthase gene (NOS3) was significantly associated with CKD after LT (P=.05; adjusted for multiple comparisons). The 5-year incidence of CKD was 70% among patients homozygous for the NOS3 variant allele (298Asp) compared with 42% among those not homozygous for the NOS3 variant allele. Specifically, homozygosity for the NOS3 variant allele conferred a 2.5-fold increased risk of developing CKD after LT (P=.005, adjusted for confounding variables).Homozygosity for the variant allele of NOS3 (298Asp) is associated with CKD after LT and may be useful for identifying recipients at higher risk of post-LT CKD.

    View details for DOI 10.4065/mcp.2010.0013

    View details for Web of Science ID 000281387500006

    View details for PubMedID 20810793

  • Donor Race Does Not Predict Graft Failure After Liver Transplantation GASTROENTEROLOGY Asrani, S. K., Lim, Y., Therneau, T. M., Pedersen, R. A., Heimbach, J., Kim, W. R. 2010; 138 (7): 2341-2347


    Donor race has been proposed to predict graft failure after liver transplantation. We evaluated the extent to which the center where the transplantation surgery was performed and other potential confounding factors might account for the observed association between donor race and graft failure.We analyzed data from the Organ Procurement and Transplantation Network (January 2003-December 2005) for adult patients undergoing primary liver transplantation in the United States. We examined the association between graft failure and the donor races of African American (AA), Caucasian, Asian/Pacific Islander (API), or those classified as other.Of 10,874 livers that were donated for transplantation, 7631 came from Caucasians, 1579 from AAs, 243 from APIs, and 1421 from others. After 36 months of follow-up evaluation, 2687 grafts failed. Without any adjustments, AA donors (hazard ratio [HR], 1.11; 95% confidence interval [CI], 1.00-1.24), API donors (HR, 1.41; 95% CI, 1.12-1.77), and other donors (HR, 1.16; 95% CI, 1.04-1.29) were associated with graft failure. After stratification by center and adjustments for age, height, and hepatitis B core antibody status of donors as well as serum creatinine and hepatitis C status of recipients, donor race was no longer statistically significant for AA (HR, 1.06; 95% CI, 0.95-1.20) and API (HR, 1.15; 95% CI, 0.89-1.49) donors. However, livers donated from members of other race still had an increased risk of graft failure (HR, 1.19; 95% CI, 1.05-1.35), although the effect was not uniform across donor-recipient pairs.Donor race is not a uniform predictor of graft failure and should not be construed as an indicator of donor quality.

    View details for DOI 10.1053/j.gastro.2010.02.008

    View details for Web of Science ID 000278136900026

    View details for PubMedID 20176028

  • Serum sodium, renal function, and survival of patients with end-stage liver disease JOURNAL OF HEPATOLOGY Lim, Y., Larson, T. S., Benson, J. T., Kamath, P. S., Kremers, W. K., Therneau, T. M., Kim, W. R. 2010; 52 (4): 523-528


    Serum creatinine, a component of the model for end-stage liver disease (MELD), is an important prognostic indicator in patients with end-stage liver disease (ESLD). In addition, serum sodium has recently been recognized as an important predictor of mortality in patients with ESLD. We investigate the role of serum creatinine and sodium, and glomerular filtration rate (GFR) as determinants of survival in patients with ESLD.A prospective database was utilized to identify all adults listed for primary liver transplantation (LTx) at the Mayo Clinic, Rochester, between 1990 and 1999. GFR was measured by iothalamate clearance.Among 837 patients listed for LTx, 660 had complete data including measured GFR. There was a significant association between GFR and survival after adjustment for MELD, with a linear rise in the risk of death as GFR decreased between 60 and 20ml/min/1.73m(2). Multivariable models showed that GFR is superior to creatinine in predicting mortality - a model consisting of total bilirubin (hazard ratio (HR)=2.17, p<0.01), INR (HR=3.26, p<0.01) and GFR (HR=0.42, p<0.01) was superior to MELD (chi-square 65.6 vs. 59.4, c-statistic 0.792 vs. 0.780). Serum sodium did not contribute to survival prediction when accurately measured GFR data were available.Serum concentrations of creatinine and sodium in patients with end-stage liver disease reflect a reduction in renal function, the underlying event that decreases survival.

    View details for Web of Science ID 000277544700011

    View details for PubMedID 20185195

    View details for PubMedCentralID PMC4546826

  • Humanistic and economic impacts of hepatitis C infection in the United States. Journal of medical economics DiBonaventura, M. D., Wagner, J., Yuan, Y., L'Italien, G., Langley, P., Ray Kim, W. 2010; 13 (4): 709-718


    Prior research examining the effect of hepatitis C virus (HCV) on health-related quality of life (HRQoL) and healthcare costs is flawed because non-patient controls were not adequately comparable to HCV patients. The current study uses a propensity score matching methodology to address the following research question: is the presence of diagnosed hepatitis C (HCV) associated with poorer health-related quality of life (HRQoL) and greater healthcare resource use?Using data from the 2009 US National Health and Wellness Survey, patients who reported a HCV diagnosis (n = 695) were compared to propensity-matched controls (n = 695) on measures of HRQoL and healthcare resource use. All analyses applied sampling weights to project to the US population.HCV patients reported significantly lower levels of HRQoL relative to the matched-control group, including the physical component score (39.6 vs. 42.7, p < 0.0001) and health utilities (0.63 vs. 0.66, p < 0.0001). The number of emergency room visits (0.59 vs. 0.44, p < 0.05) and physician visits (7.7 vs. 5.9, p < 0.05) in the past 6 months were significantly higher for the HCV group relative to matched controls.The results of this study suggest that HCV represents a substantial burden on patients by having a significant and clinically-relevant impact on key dimensions of HRQoL as well as on utilization of healthcare resources, the latter of which would result in increased direct medical costs.Due to limitations of the internet survey approach (e.g., inability to confirm HCV diagnosis), future research is needed to confirm these findings.

    View details for DOI 10.3111/13696998.2010.535576

    View details for PubMedID 21091098

  • Trends in Waiting List Registration for Liver Transplantation for Viral Hepatitis in the United States GASTROENTEROLOGY Kim, W. R., Terrault, N. A., Pedersen, R. A., Therneau, T. M., Edwards, E., Hindman, A. A., Brosgart, C. L. 2009; 137 (5): 1680-1686


    In the last decade, significant progress has been made in the treatment of liver disease associated with chronic hepatitis, especially in patients infected with the hepatitis B virus (HBV). To investigate whether the population-wide application of antiviral therapies has impacted liver transplant waiting list registration, we analyzed longitudinal trends in waiting list registration for patients with hepatitis B and C and those with nonviral liver disease.This study represented a retrospective analysis of registry data containing all US liver transplant centers. All adult, primary liver transplantation candidates registered to the Organ Procurement and Transplantation Network between 1985 and 2006 were included in the analysis. Standardized incidence rates were calculated for waiting list registration for liver transplantation by underlying disease (HBV and HCV infection and other) and by indication for transplantation (fulminant liver disease, hepatocellular carcinoma [HCC], and end-stage liver disease [ESLD]).Of 113,927 unique waiting list registrants, 4793 (4.2%) had HBV, and 40,923 (35.9%) had HCV infections; the remaining 68,211 (59.9%) had neither. The incidence of waiting list registration for ESLD and fulminant liver disease decreased, whereas that for HCC increased. The decrease in ESLD registration was most pronounced, and the increase in HCC was least dramatic among registrants with hepatitis B. The decrease in registration for ESLD secondary to HCV infection was also significantly larger than that for ESLD patients with nonviral etiologies.The pattern of liver transplantation waiting list registration among patients with hepatitis B suggests that the widespread application of oral antiviral therapy for HBV contributed to the decreased incidence of decompensated liver disease.

    View details for DOI 10.1053/j.gastro.2009.07.047

    View details for Web of Science ID 000271500700025

    View details for PubMedID 19632234

  • Impact of Pretransplant Hyponatremia on Outcome Following Liver Transplantation HEPATOLOGY Yun, B. C., Kim, W. R., Benson, J. T., Biggins, S. W., Therneau, T. M., Kremers, W. K., Rosen, C. B., Klintmalm, G. B. 2009; 49 (5): 1610-1615


    Hyponatremia is associated with reduced survival in patients with cirrhosis awaiting orthotopic liver transplantation (OLT). However, data are sparse regarding the impact of hyponatremia on outcome following OLT. We investigated the effect of hyponatremia at the time of OLT on mortality and morbidity following the procedure. The study included 2,175 primary OLT recipients between 1990 and 2000. Serum sodium concentrations obtained immediately prior to OLT were correlated with subsequent survival using proportional hazards analysis. Morbidity associated with hyponatremia was assessed, including length of hospitalization, length of intensive care unit (ICU) admission, and occurrence of central pontine myelinolysis (CPM). Out of 2,175 subjects, 1,495 (68.7%) had normal serum sodium (>135 mEq/L) at OLT, whereas mild hyponatremia (125-134 mEq/L) was present in 615 (28.3%) and severe hyponatremia (<125 mEq/L) in 65 (3.0%). Serum sodium had no impact on survival up to 90 days after OLT (multivariate hazard ratio = 1.00, P = 0.99). Patients with severe hyponatremia tended to have a longer stay in the ICU (median = 4.5 days) and hospital (17.0 days) compared to normonatremic recipients (median ICU stay = 3.0 days, hospital stay = 14.0 days; P = 0.02 and 0.08, respectively). There were 10 subjects that developed CPM, with an overall incidence of 0.5%. Although infrequent, the incidence of CPM did correlate with serum sodium levels (P < 0.01).Pre-OLT serum sodium does not have a statistically significant impact on survival following OLT. The incidence of CPM correlates with hyponatremia, although its overall incidence is low. Incorporation of serum sodium in organ allocation may not adversely affect the overall post-OLT outcome.

    View details for DOI 10.1002/hep.22846

    View details for Web of Science ID 000265668500024

    View details for PubMedID 19402063

  • Hyponatremia and mortality among patients on the liver-transplant waiting list NEW ENGLAND JOURNAL OF MEDICINE Kim, W. R., Biggins, S. W., Kremers, W. K., Wiesner, R. H., Kamath, P. S., Benson, J. T., Edwards, E., Therneau, T. M. 2008; 359 (10): 1018-1026


    Under the current liver-transplantation policy, donor organs are offered to patients with the highest risk of death.Using data derived from all adult candidates for primary liver transplantation who were registered with the Organ Procurement and Transplantation Network in 2005 and 2006, we developed and validated a multivariable survival model to predict mortality at 90 days after registration. The predictor variable was the Model for End-Stage Liver Disease (MELD) score with and without the addition of the serum sodium concentration. The MELD score (on a scale of 6 to 40, with higher values indicating more severe disease) is calculated on the basis of the serum bilirubin and creatinine concentrations and the international normalized ratio for the prothrombin time.In 2005, there were 6769 registrants, including 1781 who underwent liver transplantation and 422 who died within 90 days after registration on the waiting list. Both the MELD score and the serum sodium concentration were significantly associated with mortality (hazard ratio for death, 1.21 per MELD point and 1.05 per 1-unit decrease in the serum sodium concentration for values between 125 and 140 mmol per liter; P<0.001 for both variables). Furthermore, a significant interaction was found between the MELD score and the serum sodium concentration, indicating that the effect of the serum sodium concentration was greater in patients with a low MELD score. When applied to the data from 2006, when 477 patients died within 3 months after registration on the waiting list, the combination of the MELD score and the serum sodium concentration was considerably higher than the MELD score alone in 32 patients who died (7%). Thus, assignment of priority according to the MELD score combined with the serum sodium concentration might have resulted in transplantation and prevented death.This population-wide study shows that the MELD score and the serum sodium concentration are important predictors of survival among candidates for liver transplantation.

    View details for Web of Science ID 000258852500006

    View details for PubMedID 18768945

  • Serum aminotransferase activity and mortality risk in a United States community HEPATOLOGY Lee, T. H., Kim, W. R., Benson, J. T., Therneau, T. M., Melton, L. J. 2008; 47 (3): 880-887


    Serum aminotransferase [such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] is commonly used as an indicator of liver disease. The aim of the study was to determine the degree to which aminotransferase results are associated with increased mortality at the population level. All adult residents of Olmsted County, Minnesota, who had a health care encounter at Mayo Clinic, Rochester, in 1995 were identified and their AST or ALT results extracted from a laboratory database. These subjects were followed forward from January 1995 to April 2006 and their survival determined. To exclude patients with abnormal results because of a terminal illness, deaths within the first 2 years were excluded. The main outcome measure was survival. Standardized mortality ratios (SMRs) were calculated, based on Minnesota White death rates. During 1995, AST was measured at least once in 18,401 community residents, of whom 2,350 (13%) had results greater than the upper limit of normal (ULN). Of 6,823 subjects who had their ALT measured, 911 (13%) had results higher than ULN. Abnormal AST was associated with a significantly increased SMR (1.32 for 1-2x ULN and 1.78 for >2x ULN). SMR was also higher for abnormal ALT (SMR = 1.21 for 1-2x ULN and 1.51 for >2x ULN). In contrast, normal AST or ALT was associated with a risk of death lower than expected (SMR 0.95 for AST, 0.61 for ALT).Serum levels of AST and ALT obtained in a routine medical care setting are associated with future mortality in community residents.

    View details for DOI 10.1002/hep.22090

    View details for Web of Science ID 000253698900014

    View details for PubMedID 18302294

  • Natural history of hepatitis B virus infection: An update for clinicians MAYO CLINIC PROCEEDINGS Pungpapong, S., Kim, W. R., Poterucha, J. J. 2007; 82 (8): 967-975


    Hepatitis B virus (HBV) is a common viral pathogen that causes a substantial health burden worldwide. Significant progress has been made in the past few decades in understanding the natural history of HBV infection. A dynamic balance between viral replication and host immune response is pivotal to the pathogenesis of liver disease. In immunocompetent adults, most HBV infections spontaneously resolve, whereas in most neonates and infants they become chronic. Those with chronic HBV may present in 1 of 4 phases of infection: (1) in a state of immune tolerance, (2) with hepatitis B e antigen (HBeAg)positive chronic hepatitis, (3) as an inactive hepatitis B surface antigen carrier, or (4) with HBeAg-negative chronic hepatitis. Of these, HBeAg-positive and HBeAg-negative chronic hepatitis may progress to cirrhosis and its long-term sequelae including hepatic decompensation and hepatocellular carcinoma. Several prognostic factors, such as serum HBV DNA concentrations, HBeAg status, serum aminotransferases, and certain HBV genotypes, have been identified to predict long-term outcome. These data emphasize the importance of monitoring all patients with chronic HBV infection to identify candidates for and select optimal timing of antiviral treatment, to recognize those at risk of complications, and to implement surveillance for early detection of hepatocellular carcinoma.

    View details for Web of Science ID 000248661700010

    View details for PubMedID 17673066

  • Evidence-based incorporation of serum sodium concentration into MELD GASTROENTEROLOGY Biggins, S. W., Kim, W. R., Terrault, N. A., Saab, S., Balan, V., Schiano, T., Benson, J., Therneau, T., Kremers, W., Wiesner, R., Kamath, P., Klintmalm, G. 2006; 130 (6): 1652-1660


    Serum sodium (Na) concentrations have been suggested as a useful predictor of mortality in patients with end-stage liver disease awaiting liver transplantation.We evaluated methods to incorporate Na into model for end-stage liver disease (MELD), using a prospective, multicenter database specifically created for validation and refinement of MELD. Adult, primary liver transplant candidates with end-stage liver disease were enrolled.Complete data were available in 753 patients, in whom the median MELD score was 10.8 and sodium was 137 mEq/L. Low Na (<130 mEq/L) was present in 8% of patients, of whom 90% had ascites. During the study period, 67 patients (9%) died, 243 (32%) underwent transplantation, 73 (10%) were withdrawn, and 370 were still waiting. MELD score and Na, at listing, were significant (both, P < .01) predictors of death within 6 months. After adjustment for MELD score and center, there was a linear increase in the risk of death as Na decreased between 135 and 120 mEq/L. A new score to incorporate Na into MELD was developed: "MELD-Na" = MELD + 1.59 (135 - Na) with maximum and minimum Na of 135 and 120 mEq/L, respectively. In this cohort, "MELD-Na" scores of 20, 30, and 40 were associated with 6%, 16%, and 37% of risk of death within 6 months of listing, respectively. If this new score were used to allocate grafts, it would affect 27% of the transplant recipients.We demonstrate an evidence-based method to incorporate Na into MELD, which provides more accurate survival prediction than MELD alone.

    View details for DOI 10.1053/j.gastro.2006.02.010

    View details for Web of Science ID 000237686700016

    View details for PubMedID 16697729

  • Deaths on the liver transplant waiting list: An analysis of competing risks HEPATOLOGY Kim, W. R., Therneau, T. M., Benson, J. T., Kremers, W. K., Rosen, C. B., Gores, G. J., Dickson, E. R. 2006; 43 (2): 345-351


    The usual method of estimating survival probabilities, namely the Kaplan-Meier method, is suboptimal in the analysis of deaths on the transplant waiting list. Death, transplantation, and withdrawal from list must all be considered. In this analysis, we applied the competing risk analysis method, which allows evaluating these end points individually and simultaneously, to compare the risk of waiting list death across era, blood types, liver disease diagnosis, and severity (Model for End-stage Liver Disease; MELD). Of 861 patients registered on the waiting list at Mayo Clinic Rochester between 1990 and 1999, 657 (76%) patients underwent transplantation, 82 (10%) died while waiting, 41 (5%) withdrew from the list, and 81 (9%) patients were still waiting as of February 2002. The risk of death at 3 years was 10% by the competing risk analysis. During the study period, the median time to transplantation increased from 45 to 517 days. In univariate analyses, there was no significant difference in the risk of death by era of listing (P = .25) or blood type (P = .31), whereas the risk of death was significantly higher in patients with alcohol-induced liver disease and those with higher MELD score (P < .01). A multivariable analysis showed that after adjusting for MELD, blood type, and diagnosis, patients listed in the latter era had higher mortality. In conclusion, the competing risk analysis method is useful in estimating the risk of death among patients awaiting liver transplantation.

    View details for DOI 10.1002/bep.21025

    View details for Web of Science ID 000235112900016

    View details for PubMedID 16440361

  • Mortality and hospital utilization for hepatocellular carcinoma in the United States GASTROENTEROLOGY Kim, W. R., Gores, G. J., Benson, J. T., Therneau, T. M., Melton, L. J. 2005; 129 (2): 486-493


    The incidence of hepatocellular carcinoma (HCC) has been increasing in the United States. Although resource-intensive treatment modalities have been increasingly applied, these patients still have poor survival. We examined 2 nationally representative databases, the Multiple Cause of Death file and the Nationwide Inpatient Sample database, to examine trends in mortality and hospital service utilization related to HCC.In both databases, a priori criteria were used to identify cases of HCC. All other available diagnostic fields were examined to characterize coexistent liver disease. Age-, sex-, and race-specific mortality from HCC was calculated, and temporal changes in mortality rates were evaluated using the multivariable Poisson model. Hospital service utilization was estimated based on length of stay, total hospitalization charges, and principal procedures.The age-, sex-, and race-specific mortality from HCC increased from 1.54 to 2.58 per 100,000 per year between 1980 and 1998. Male sex, African and Asian race, and increasing age were also associated with higher mortality. The estimated total charge for HCC hospitalizations nationwide increased from 241 million US dollars in 1988 to 509 million US dollars in 2000 after inflation adjustment. Commonly employed procedures in 2000 included angiography/embolization, resection, local ablative therapy, and liver transplantation.In the recent past, mortality and hospital service utilization related to HCC increased substantially. Closer epidemiologic surveillance to understand causation of HCC at the population level and to help implement primary and secondary prevention is urgently warranted.

    View details for DOI 10.1053/j.gastro.2005.05.001

    View details for Web of Science ID 000231070600012

    View details for PubMedID 16083705

  • The use of decision analytic models to inform clinical decision making in the management of hepatocellular carcinoma. Clinics in liver disease Kim, W. R. 2005; 9 (2): 225-234


    Decision analysis helps evaluate competing strategies under conditions of uncertainty in a wide variety of clinical settings. Despite some limitations, decision trees and Markov models remain essential tools for medical decision analysts. These techniques allow comparison of competing management strategies in a quantitative fashion. Sensitivity analysis is an important feature of decision analytic models that identify important factors that affect the outcome of decisions under considerations. Judiciously used, decision analytic models allow a quantitative evaluation of existing data as they relate to strategies ranging from optimizing clinical management at the patient level to allocating health care resources at the societal level.

    View details for PubMedID 15831270

  • MELD accurately predicts mortality in patients with alcoholic hepatitis HEPATOLOGY Dunn, W., Jamil, L. H., Brown, L. S., Wiesner, R. H., Kim, W. R., Menon, K. V., Malinchoc, M., Kamath, P. S., Shah, V. 2005; 41 (2): 353-358


    Assessing severity of disease in patients with alcoholic hepatitis (AH) is useful for predicting mortality, guiding treatment decisions, and stratifying patients for therapeutic trials. The traditional disease-specific prognostic model used for this purpose is the Maddrey discriminant function (DF). The model for end-stage liver disease (MELD) is a more recently developed scoring system that has been validated as an independent predictor of patient survival in candidates for liver transplantation. The aim of the present study was to examine the ability of MELD to predict mortality in patients with AH. A retrospective cohort study of 73 patients diagnosed with AH between 1995 and 2001 was performed at the Mayo Clinic in Rochester, Minnesota. MELD was the only independent predictor of mortality in patients with AH. MELD was comparable to DF in predicting 30-day mortality (c-statistic and 95% CI: 0.83 [0.71-0.96] and 0.74 [0.62-0.87] for MELD and DF, respectively, not significant) and 90-day mortality (c-statistic and 95% CI: 0.86 [0.77-0.96] and 0.83 [0.74-0.92] for MELD and DF, respectively, not significant). A MELD score of 21 had a sensitivity of 75% and a specificity of 75% in predicting 90-day mortality in AH. In conclusion, MELD is useful for predicting 30-day and 90-day mortality in patients with AH and maintains some practical and statistical advantages over DF in predicting mortality rate in these patients. MELD is a useful clinical tool for gauging mortality and guiding treatment decisions in patients with AH, particularly those complicated by ascites and/or encephalopathy.

    View details for DOI 10.1002/hep.20503

    View details for Web of Science ID 000226637900017

    View details for PubMedID 15660383

  • Effect of minimal listing criteria on waiting list registration for liver transplantation: A process-outcome analysis 51st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases Talwalkar, J. A., Kim, W. R., Rosen, C. B., Kamath, P. S., Wiesner, R. H. MAYO CLINIC PROCEEDINGS. 2003: 431–35


    To determine the level of association between minimal listing criteria (MLC) recognition and outcomes associated with waiting list registration for liver transplantation (LT).A total of 147 patients and 201 patients were identified as first-time referrals for LT evaluation between January 1, 1997, and November 30, 1997 (cohort A), and December 1,1997, and December 31, 1998 (cohort B), respectively. Relevant demographic and clinical information was abstracted from medical records. Minimal listing criteria were defined as a Child-Turcotte-Pugh (CTP) score of 7 or higher.Patient age, sex, hepatic disease etiology, and mean CTP scores were similar between cohorts A and B. However, the proportion of registered patients in cohort B with CTP scores of 7 or higher increased significantly after formal MLC recognition (96% vs 82% for cohort A; P=.001). In cohort A, waiting list registration was based on patient age, male sex, nonalcohol-related hepatic disease, and a CTP score of 7 or higher in the absence of formal MLC. The rate of first-time patient referral was also increased in cohort B vs cohort A after formal MLC recognition (80% vs 69%, respectively; P=.002) despite similar clinical characteristics. Although the number of patients with a CTP score of 10 or higher was greater in cohort B vs cohort A, the proportion of patients with advanced end-stage liver disease was similar (29% vs 26%, respectively; P=.72).The explicit recognition of MLC was strongly associated with improvements in appropriate waiting list registration for LT.

    View details for Web of Science ID 000181946600005

    View details for PubMedID 12683695

  • Medical and economic impact of autoimmune hepatitis. Clinics in liver disease Talwalkar, J. A., Kim, W. R. 2002; 6 (3): 649-667


    AIH is a chronic liver disease that has been associated with hepatic failure and death in the absence of liver transplantation. As a result, AIH imparts significant medical and economic burdens on affected patients and health care delivery systems, respectively. The use of accepted methodologies for outcomes and health services research has identified emerging information on the epidemiology and natural history, HRQoL, and resource utilization for similar autoimmune chronic liver diseases such as PBC and PSC. Similar efforts are needed in AIH, and they are supported on the basis of existing data which suggest similar levels of disease burden compared to PBC and PSC. As a result, the ability to plan for disease management strategies in AIH that require the allocation of scarce resources will be feasible.

    View details for PubMedID 12362573

  • Reliability and validity of the NIDDK-QA instrument in the assessment of quality of life in ambulatory patients with cholestatic liver disease HEPATOLOGY Kim, W. R., Lindor, K. D., Malinchoc, M., Petz, J. L., Jorgensen, R., Dickson, E. R. 2000; 32 (5): 924-929


    The NIDDK-QA instrument, developed and widely used in liver transplant recipients, assesses quality of life (QOL) in four domains, including liver disease symptoms, physical function, health satisfaction, and overall well-being. We investigated whether the instrument may be used as a disease-specific instrument in ambulatory patients with cholestatic liver disease. The NIDDK-QA instrument was administered in 96 patients with primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) seen at the Mayo Clinic. The SF-36, a well-established generic instrument, was also administered. Standard measures for test-retest reliability, internal consistency, and discriminant and concurrent validity were examined. All patients were ambulatory with mostly normal levels of serum bilirubin and albumin concentrations. The reliability of the NIDDK-QA, as measured by test-retest correlation (Pearson coefficients: 0.82-0.99, P <.01) and by internal consistency (Cronbach's alpha: 0.87-0.94) exceeded conventional acceptability criteria. The correlation between domain scores of the NIDDK-QA and SF-36 was clear and logical in that the physical function domain of NIDDK-QA strongly correlated with the physical component summary score of SF-36 (r = 0.86, P <.01). The overall well-being domain of the NIDDK-QA was closely associated with the mental summary score of SF-36 (r = 0.69, P <.01). Among PBC patients, there was a modest yet significant correlation between the Mayo risk score and overall well-being (r = -0.26, P =.03). In the assessment of QOL in patients with cholestatic liver disease, NIDDK-QA is found reliable and valid. These data, combined with our previous study, demonstrate its applicability in a wide spectrum of disease severity, ranging from early, ambulatory-phase disease to decompensated cirrhosis necessitating liver transplantation.

    View details for DOI 10.1053/jhep.2000.19067

    View details for Web of Science ID 000090061000006

    View details for PubMedID 11050040

  • A revised natural history model for primary sclerosing cholangitis MAYO CLINIC PROCEEDINGS Kim, W. R., Therneau, T. M., Wiesner, R. H., Poterucha, J. J., Benson, J. T., Malinchoc, M., LaRusso, N. F., Lindor, K. D., Dickson, E. R. 2000; 75 (7): 688-694


    To describe a natural history model for primary sclerosing cholangitis (PSC) that is based on routine clinical findings and test results and eliminates the need for liver biopsy.Using the Cox proportional hazards analysis, we created a survival model based on 405 patients with PSC from 5 clinical centers. Independent validation of the model was undertaken by applying it to 124 patients who were not included in the model creation.Based on the multivariate analysis of 405 patients, a risk score was defined by the following formula: R = 0.03 (age [y]) + 0.54 loge (bilirubin [mg/dL]) + 0.54 loge (aspartate aminotransferase [U/L]) + 1.24 (variceal bleeding [0/1]) - 0.84 (albumin [g/dL]). The risk score was used to obtain survival estimates up to 4 years of follow-up. Application of this model to an independent group of 124 patients showed good correlation between estimated and actual survival.A new model to estimate patient survival in PSC includes more reproducible variables (age, bilirubin, albumin, aspartate aminotransferase, and history of variceal bleeding), has accuracy comparable to previous models, and obviates the need for a liver biopsy.

    View details for Web of Science ID 000088050900004

    View details for PubMedID 10907383

  • Variant forms of cholestatic diseases involving small bile ducts in adults AMERICAN JOURNAL OF GASTROENTEROLOGY Kim, W. R., Ludwig, J., Lindor, K. D. 2000; 95 (5): 1130-1138


    Cholestasis may result from diverse etiologies. We review chronic cholestatic disorders involving small intrahepatic bile ducts in the adult ambulatory care setting. Specifically, we discuss variant forms of primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) as well as other conditions that may present diagnostic and therapeutic difficulties.We conducted a MEDLINE search of the literature (1981-1997) and reviewed the experiences at the Mayo Clinic. All articles were selected that discussed antimitochondrial antibody (AMA)-negative PBC, small-duct PSC (formerly pericholangitis), and idiopathic adulthood ductopenia.The most common chronic cholestatic liver diseases affecting adults are PBC and PSC. Patients without the hallmarks of either syndrome are diagnosed according to their clinical and histological characteristics. Autoimmune cholangitis is diagnosed if clinical and histological features are compatible with PBC but autoantibodies other than AMA are present. Isolated small duct PSC is diagnosed if patients have inflammatory bowel disease, biopsy features compatible with PSC, but a normal cholangiogram. If ductopenia (absence of interlobular bile ducts in small portal tracts) is found histologically in the absence of PSC, inflammatory bowel disease, and other specific cholestatic syndromes such as drug reaction or sarcoidosis, the most likely diagnosis is idiopathic adulthood ductopenia.Based on these definitions, an algorithm for diagnosis and therapy in patients with laboratory evidence of chronic cholestasis may be constructed, pending results of further investigations into the etiopathogenesis of these syndromes.

    View details for Web of Science ID 000086853300006

    View details for PubMedID 10811317

  • Hepatic retransplantation in cholestatic liver disease: Impact of the interval to retransplantation on survival and resource utilization HEPATOLOGY Kim, W. R., Wiesner, R. H., Poterucha, J. J., Therneau, T. M., Malinchoc, M., Benson, J. T., Crippin, J. S., Klintmalm, G. B., Rakela, J., Starzl, T. E., Krom, R. A., Evans, R. W., Dickson, E. R. 1999; 30 (2): 395-400


    The aim of our study was to quantitatively assess the impact of hepatic retransplantation on patient and graft survival and resource utilization. We studied patients undergoing hepatic retransplantation among 447 transplant recipients with primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) at 3 transplantation centers. Cox proportional hazards regression analysis was used for survival analysis. Measures of resource utilization included the duration of hospitalization, length of stay in the intensive care unit, and the duration of transplantation surgery. Forty-six (10.3%) patients received 2 or more grafts during the follow-up period (median, 2.8 years). Patients who underwent retransplantation had a 3.8-fold increase in the risk of death compared with those without retransplantation (P <.01). Retransplantation after an interval of greater than 30 days from the primary graft was associated with a 6.7-fold increase in the risk of death (P <.01). The survival following retransplantations performed 30 days or earlier was similar to primary transplantations. Resource utilization was higher in patients who underwent multiple consecutive transplantations, even after adjustment for the number of grafts during the hospitalization. Among cholestatic liver disease patients, poor survival following hepatic retransplantation is attributed to late retransplantations, namely those performed more than 30 days after the initial transplantation. While efforts must be made to improve the outcome following retransplantation, a more critical evaluation may be warranted for late retransplantation candidates.

    View details for Web of Science ID 000081711500007

    View details for PubMedID 10421646

  • Quality of life before and after liver transplantation for cholestatic liver disease HEPATOLOGY Gross, C. R., Malinchoc, M., Kim, W. R., Evans, R. W., Wiesner, R. H., Petz, J. L., Crippin, J. S., Klintmalm, G. B., Levy, M. F., Ricci, P., Therneau, T. M., Dickson, E. R. 1999; 29 (2): 356-364


    Liver transplantation (LT) is an established therapy for patients with end-stage primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC). In this report, we describe the health status and quality of life (QOL) in patients with these cholestatic liver diseases before and after LT. A QOL questionnaire was completed by 157 adult patients with PBC or PSC before and 1 year after liver transplantation at the Mayo Clinic or Baylor University Medical Center. This questionnaire measured four aspects of QOL, including symptoms; physical, social, and emotional functioning; health perceptions; and overall QOL. Changes in these QOL parameters before and after LT were described, and regression analysis was used to assess the relationships between clinical and QOL factors. There were no differences in QOL parameters between patients with PBC and PSC. QOL following transplantation was substantially better than before transplantation. This was observed in all four aspects of QOL. The degree of improvement as measured by effect size (difference in mean scores divided by the pretransplantation standard deviation) was 0.53 for symptoms (P <.01), 1.16 for function (P <.01), 2.37 for health satisfaction (P <.01), and 1.16 for overall QOL (P <.01). Patients' overall QOL before transplantation was significantly related to subjective and objective health status indicators and clinical factors such as ascites and renal dysfunction. QOL at 1-year follow-up, however, could not be adequately predicted by the pretransplantation subjective health status and clinical factors. Patients with end-stage cholestatic disease undergoing LT experience substantial improvement in all aspects of QOL addressed in this study. The patients' QOL 1 year after LT could not be predicted by pretransplantation variables used in this study.

    View details for Web of Science ID 000078333900007

    View details for PubMedID 9918910

  • Predictive models of natural history in primary biliary cirrhosis. Clinics in liver disease Kim, W. R., Dickson, E. R. 1998; 2 (2): 313-?


    Primary biliary cirrhosis is a slow, progressive disease. Although many years may elapse before asymptomatic primary biliary cirrhosis patients begin experiencing symptoms of liver disease, their overall survival is significantly lower than the normal population. The Mayo natural history model has been developed to depict patient survival in the absence of effective therapeutic intervention. Although there are a number of caveats in applying this model, it has been validated using external data sets and established as an accepted tool for clinical or research purposes. Furthermore, recent data suggest that the Mayo natural history model continues to provide useful, predictive information in the presence of ursodeoxycholic acid therapy, which has been shown to lower the serum bilirubin to the natural history model for patient survival. In addition to the natural history model for patient survival, mathematical models have been developed to describe histologic progression and development of esophageal varices.

    View details for PubMedID 15560035

  • The role of prognostic models in the timing of liver transplantation. Application in cholestatic liver diseases. Clinics in liver disease Kim, W. R., Dickson, E. R. 1997; 1 (2): 263-?


    Prognostic models have been developed for patients with primary biliary cirrhosis and primary sclerosing cholangitis to predict survival without transplantation. In patients undergoing liver transplantation, these models have been used in assessing postoperative mortality and morbidity. Recent data suggest that preoperative recipient physiology, such as impaired functional status or renal insufficiency, is the most important determinant of transplant outcome. Survival, quality of life, morbidities and resource use are the key variables to be considered in the timing of transplantation.

    View details for PubMedID 15562568

  • Does antimitochondrial antibody status affect response to treatment in patients with primary biliary cirrhosis? Outcomes of ursodeoxycholic acid therapy and liver transplantation HEPATOLOGY Kim, W. R., Poterucha, J. J., Jorgensen, R. A., Batts, K. P., Homburger, H. A., Dickson, E. R., Krom, R. A., Wiesner, R. H., Lindor, K. D. 1997; 26 (1): 22-26


    Approximately 5% to 10% of patients with features otherwise consistent with primary biliary cirrhosis (PBC) lack antimitochondrial antibodies (AMA). Most of these patients have other autoantibodies, a syndrome recently named "autoimmune cholangitis." We report our experience in patients with AMA-negative PBC treated with ursodeoxycholic acid (UDCA) and/or liver transplantation (OLT). The study of response to UDCA was performed as follows. While recruiting patients for a previously reported multicenter trial, we identified 8 patients with AMA-negative PBC. The patients were given UDCA and followed up at regular intervals. The characteristics of AMA-negative patients at presentation were similar to those of AMA-positive patients with PBC. The clinical outcomes and sequential liver biochemistries of UDCA treatment were also comparable with those of AMA-positive patients. The study of outcome of OLT was performed as follows. We identified OLT recipients at the Mayo Clinic who had clinical, radiological, and histological features compatible with PBC. Their pretransplant AMA status was determined, and each AMA-negative patient was paired with 2 AMA-positive patients. Of 85 OLT recipients with a diagnosis of PBC, 6 (7.1%) were AMA negative, including 1 who had undergone UDCA therapy. After a median of 36 months of follow-up, graft and patient survival rates and subsequent histological changes (disease recurrence and steroid-resistant or late rejections) were comparable in AMA-negative and -positive PBC patients. In summary, in our experience of 13 AMA-negative PBC patients (including 9 who met the criteria for a diagnosis of autoimmune cholangitis), treatment with UDCA or OLT resulted in similar outcomes to those found in AMA-positive patients. We conclude that AMA status does not affect the response in PBC patients to treatment with UDCA or OLT.

    View details for Web of Science ID A1997XH50100004

    View details for PubMedID 9214447

  • Preoperative predictors of resource utilization in liver transplantation. Clinical transplants Kim, W. R., Therneau, T. M., Dickson, E. R., Evans, R. W. 1995: 315-322


    Orthotopic liver transplantation (OLT) has been shown to be effective in prolonging life and improving its quality in patients with end-stage liver disease. However, it remains one of the most expensive surgical procedures performed today. In an era when economic efficiency and financial accountability are being emphasized, it is imperative to consider resource utilization in evaluating candidates for OLT. We prospectively followed 106 patients who underwent OLT at the Mayo Clinic for primary biliary cirrhosis and primary sclerosing cholangitis between 1990 and 1994. Hospital and professional charges for the initial hospitalization were obtained on all patients. Univariate and multivariate models were constructed using preoperative clinical variables that had been previously found to be important in predicting clinical outcomes. The preoperative variables considered were age, gender, diagnosis of liver disease, Mayo risk score, Child's score, nutritional status, Karnofsky score, INR, serum levels of albumin, bilirubin, and creatinine, and the presence/absence of ascites, edema, encephalopathy, renal failure (serum creatinine >2.0) and gastrointestinal bleeding. Of the 106 patients, 3 were excluded from the analysis because they received multiple transplants during the initial hospitalization. Of the hospital charges we analyzed, the surgical fee for transplantation and donor acquisition expense were fixed in advance and, therefore, excluded. The following preoperative variables were found to be significant in the univariate analysis: Mayo risk score, Child's score, nutritional status, Karnofsky score, INR, serum levels of bilirubin and creatinine, presence of renal failure, and gastrointestinal bleeding. In the multivariate analyses, Karnofsky score of 40 or less was associated with a 48% increase in total charges. Poor nutritional status and renal failure were associated with a 34% and 31% increase, respectively. We identified 3 preoperative variables as significant independent predictors of resource utilization in liver transplantation. In an effort to maximize the economic efficiency with which liver transplantation is performed, we believe these factors should be taken into consideration in determining both the timing of transplantation and the suitability of potential transplant recipients.

    View details for PubMedID 8794277