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

Academic Appointments

Administrative Appointments

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

Boards, Advisory Committees, Professional Organizations

  • Senior Fellow, Center for Innovation in Global Health (2015 - Present)
  • Treasurer, AASLD (2014 - Present)
  • Chair, Development Committee, AASLD (2011 - 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)


Stanford Advisees


All Publications

  • 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) ?2 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 ?2 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

  • 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

  • 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 HEPATOLOGY Flemming, J. A., Vittinghoff, E., Kim, W. R., Terrault, N. 2013; 58: 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

  • 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

  • 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

  • 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

  • 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

  • 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

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