Gabriel Garcia

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of mortality worldwide. Existing studies comparing outcomes after liver transplantation (LT) versus surgical resection among transplant-eligible patients are conflicting.The purpose of this study was to compare long-term survival between consecutive transplant-eligible HCC patients treated with resection versus LT.The present retrospective matched case cohort study compares long-term survival outcomes between consecutive transplant-eligible HCC patients treated with resection versus LT using intention-to-treat (ITT) and as-treated models. Resection patients were matched to LT patients by age, sex, and etiology of HCC in a 1:2 ratio.The study included 171 patients (57 resection and 114 LT). Resection patients had greater post-treatment tumor recurrence (43.9 vs. 12.9 %, p < 0.001) compared to LT patients. In the as-treated model of the pre-model for end stage liver disease (MELD) era, LT patients had significantly better 5-year survival compared to resection patients (100 vs. 69.5 %, p = 0.04), but no difference was seen in the ITT model. In the multivariate Cox proportional hazards model, inclusive of age, sex, ethnicity, tumor stage, and MELD era (pre-MELD vs. post-MELD), treatment with resection was an independent predictor of poorer survival (HR 2.72; 95 % CI, 1.08-6.86).Transplant-eligible HCC patients who received LT had significantly better survival than those treated with resection, suggesting that patients who can successfully remain on LT listing and actually undergo LT have better outcomes.

View details for DOI 10.1007/s10620-013-2947-8

View details for PubMedID 24282054

Abstract

The incidence of hepatocellular carcinoma (HCC) is higher in Asian Americans than in other ethnicities. While hepatitis B virus (HBV) is common, hepatitis C virus (HCV) is more prevalent in some subgroups. Our goal was to determine the etiology of liver disease associated with HCC in subgroups of Asian Americans. This was an analysis of 510 Asian HCC patients at a US medical center. Patients were identified using ICD9 diagnosis. Multivariate logistic regression was used to study predictors of HCV as the cause of HCC. Patients were Southeast Asian, Chinese, and Korean, with similar gender, age, and foreign-born status. Southeast Asians had a similar proportion of HBV- and HCV-related HCC, while Chinese and Korean patients had a higher proportion of HBV-related HCC. HCC was usually associated with HBV in Chinese and Korean patients, but both HCV and HBV were important associations in Southeast Asians.

View details for DOI 10.1007/s10903-013-9871-z

View details for PubMedID 23864445

Abstract

Treatment end-point of therapy for patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) includes HBeAg seroconversion, which ranges from 15% to 22% after 1 year of oral nucleos(t)ides according to clinical trials. Our goal was to determine the incidence and predictors of HBeAg seroconversion in such patients in routine clinical practice because they may differ than reported rates.We conducted a retrospective cohort study of 333 consecutive treatment-naïve HBeAg-positive patients who were treated for CHB between 1/2000 and 6/2010 at three gastroenterology and liver clinics in the USA. Primary study end-point was HBeAg seroconversion-loss of HBeAg and antibody to HBeAg (anti-HBe) development.The majority of patients were Asian (96%). Median treatment duration prior to HBeAg seroconversion was 50 (range 26-52) weeks. Of the 333 study patients, 25% received lamivudine, 16% adefovir, 51% entecavir, and 8% tenofovir. HBeAg seroconversion at month 12 was 8.2%. On multivariate analysis inclusive of age, gender, and antiviral agents, independent predictors for HBeAg seroconversion at month 12 were hepatitis B virus DNA ?1.5?×?upper normal limit (HR?=?2.86 [1.05-7.81], P?=?0.040), but not the choice of nucleos(t)ides.The HBeAg seroconversion rate seen in clinical settings for oral nucleos(t)ides appears much lower than those reported in pivotal trials, especially in patients with lower ALT and higher HBV DNA levels. HBeAg-positive patients should be counseled about the high possibility of the long treatment duration required to achieve recommended treatment end-points.

View details for DOI 10.1111/jgh.12108

View details for PubMedID 23278507

Abstract

Data from registration trials with highly selective patients have shown that hepatitis B envelope antigen (HBeAg)-positive patients with chronic hepatitis B respond well to entecavir (ETV) 0.5 mg daily, with an HBeAg seroconversion rate of 21% at 12 months. However, there are varying data on the treatment outcomes of ETV 0.5 mg daily in routine clinical settings, with seroconversion rates at 12 months ranging from 8 to 48% in studies limited to 44-90 patients from centers in Asia, Europe, and South America.In the present study, we examined long-term treatment efficacy and tolerability in 136 consecutive treatment-naive HBeAg-positive chronic hepatitis B patients treated between January 2005 and January 2011 with ETV 0.5 mg daily at community clinics and tertiary centers in the USA. The primary study end point was HBeAg seroconversion.Sixty-one percent of HBeAg-positive patients were men, mean age 39 ± 12 years, median hepatitis B virus DNA 7.48 (3.7-9.8) log10 IU/ml, median alanine aminotransferase 67 (14-1077) U/l, and median treatment duration 18 (6-60) months. At months 12, 24, and 36, complete viral suppression rates were 41, 66, and 85% and HBeAg seroconversion rates were 4.8, 20, and 30%, respectively. No patients experienced adverse events or developed genotypic resistance to ETV.In clinical settings, ETV is highly tolerable and potent at suppressing hepatitis B viremia; however, the rates of HBeAg seroconversion appear to be much lower than those reported, highlighting the importance of appropriate counseling and planning for long-term therapy.

View details for DOI 10.1097/MEG.0b013e32835b3677

View details for Web of Science ID 000314633700011

View details for PubMedID 23169311

Abstract

Prior studies have shown that precore mutations abolish and basal core promoter (BCP) mutations down-regulate hepatitis B e antigen (HBeAg) production. Thus, the presence of precore and BCP mutations in HBeAg-positive patients indicates an infection with a mixed viral population of wild-type and precore and/or BCP mutant hepatitis B virus (HBV). To date, there has been limited study of the prevalence and clinical significance of precore and BCP mutations in patients with HBeAg-positive chronic hepatitis B.To determine the prevalence, predictors and clinical characteristics of mixed wild-type and precore/BCP HBV infection, through a cross-sectional study, in a US cohort of patients with chronic hepatitis B.We conducted a retrospective study of 828 chronic hepatitis B patients with HBV genotype and mutation panel testing seen at three US gastroenterology and liver clinics from June 2005 to September 2009.A majority of our patients (92.3%) were either Vietnamese or Chinese American. In the HBeAg-positive cohort, 17% of patients had precore mutations only, 28% had BCP mutations only and 5% had both BCP and precore mutations. On multivariate analyses, HBV genotype C, increasing age, lower HBV DNA level and an ALT quotient >2 were independent predictors for the presence of precore and/or BCP mutations.The current distinction and management recommendations for HBeAg-positive vs. HBeAg-negative patients with chronic hepatitis B should be reassessed. Additional biomarkers and treatment endpoints should be studied for their usefulness in predicting continued viral suppression after treatment discontinuation.

View details for DOI 10.1111/apt.12193

View details for Web of Science ID 000313891900011

View details for PubMedID 23278246

Abstract

We aimed to identify risk factors for hepatocellular carcinoma (HCC) in patients with cirrhosis in the United States. We performed a prospective study to identify associations between etiologies of cirrhosis and ethnicity with HCC incidence.We used convenience sampling to select a cohort of 379 patients with cirrhosis who visited the liver clinic at the Stanford University Medical Center from 2001 to 2009 (65% male, 75% white or Hispanic, and 20% Asian). Study end points were HCC diagnosis by histology or noninvasive criteria, liver transplantation, or last screening without HCC. Patients were followed up, with ultrasound or computed tomographic imaging analyses and measurements of serum levels of ?-fetoprotein, approximately every 6 months, for a median time of 34 months (range, 6-99 mo).The etiologies of cirrhosis in the cohort were 68% hepatitis C, 7% hepatitis B, and 25% nonviral. Forty-four patients (12%) were diagnosed with HCC during the follow-up period. Patients with cirrhosis related to viral hepatitis had a statistically significantly higher incidence of HCC than those with nonviral diseases in Kaplan-Meier analysis (P = .04). There was no statistically significant difference in HCC incidence between Asian and non-Asian patients. In a multivariate Cox proportional hazards model that included age, sex, ethnicity, etiology, and Child-Pugh-Turcotte score, viral cirrhosis was associated significantly with HCC, compared with nonviral cirrhosis (hazard ratio, 3.6; 95% confidence interval, 1.3-10.1; P = .02) but Asian ethnicity was not.In a diverse cohort of patients in the United States with cirrhosis, a viral etiology of cirrhosis was associated with increased incidence of HCC, but Asian ethnicity was not. These findings indicate the importance of cirrhosis etiology in determining risk for HCC.

View details for DOI 10.1016/j.cgh.2012.08.011

View details for Web of Science ID 000312265900021

View details for PubMedID 22902757

Abstract

The primary treatment endpoint for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B is HBeAg seroconversion; however, data on the durability of response are inconsistent.Our goal was to investigate the rate of recurrent viremia after HBeAg seroconversion and subsequent discontinuation of therapy.We retrospectively studied 88 consecutive Asian American patients who achieved HBeAg seroconversion [loss of HBeAg and development of antibody to HBeAg (anti-HBe)] among 458 HBeAg-positive patients who received oral antiviral therapy at 3 US clinics between March 1998 and November 2010. Recurrent viremia was defined as reappearance of detectable serum hepatitis B virus DNA (>100 IU/mL) on 2 consecutive laboratory tests from previously undetectable levels.Antiviral medications used at the time of HBeAg seroconversion included: lamivudine (23%), adefovir (34%), entecavir (36%), tenofovir (4%), and combination therapy (3%). Antiviral therapy was continued after HBeAg seroconversion in 49 patients (group I) and discontinued in the other 39 patients after consolidation therapy [median=12 months (range, 1 to 55 mo)] (group II). No patients in group I experienced recurrent viremia, whereas 90% in group II did. Elevated alanine aminotransferase also occurred in 38% of group II patients [median peak alanine aminotransferase 249 IU/mL (range, 93 to 1070 IU/mL)].Despite consolidation therapy, almost all patients who discontinued therapy after achieving HBeAg seroconversion and complete viral suppression experienced recurrent viremia, and close to half also experienced biochemical flares. HBeAg seroconversion does not seem to be a durable treatment endpoint for many patients, and they should be monitored carefully for virologic relapse and biochemical flares if antiviral therapy is withdrawn.

View details for DOI 10.1097/MCG.0b013e31825ceed9

View details for Web of Science ID 000312953400018

View details for PubMedID 22941429

Abstract

The majority of data on risk factors (RFs) for hepatocellular carcinoma (HCC) comes from studies involving populations without underlying liver disease. It is important to evaluate RFs for HCC in patients with chronic liver disease since HCC rarely occurs in those without underlying liver disease. We conducted a hospital-based case-control study of 259 incident HCC cases and 781 controls by convenience sampling between 02/2001 and 12/2009 from the liver clinic at Stanford University Medical Center. The study population was 41% White, 14% Hispanic, 3% African American, 40% Asian American, and 2% other race/ethnicity. RFs were examined through medical records and an in-person questionnaire. Alcohol and tobacco use was calculated by cumulative grams of alcohol or cumulative pack(s) of cigarette consumed over one's lifetime. Diabetes mellitus (DM) was defined by random glucose level of ?200 mg/dL. RFs were evaluated using multivariate logistic regression. Independent predictors of HCC risk, after mutual adjustment and additional control for alcohol use, etiology of liver diseases, and DM, included age >40 (OR = 8.5 [2.6-28.3]), male gender (OR = 3.5 [2.2-5.8]), presence of cirrhosis (OR = 2.8 [1.6-4.9]), Asian ethnicity (OR = 2.8 [1.8-4.6]), AFP > 50 (OR = 4.2 [2.6-6.8]), and cumulative lifetime tobacco use of >11,000 packs (OR = 1.7 [1.0-2.9]). Heavy prolonged cigarette smoking, but not alcohol use, was a significant independent predictor for HCC in patients with underlying liver disease. Besides older age, male gender, presence of cirrhosis, and elevated AFP, Asian ethnicity and heavy cumulative tobacco use are strong independent predictors of HCC.

View details for DOI 10.1007/s10552-012-9895-z

View details for Web of Science ID 000300891100006

View details for PubMedID 22258434

Abstract

Commonly known risk factors for infection with hepatitis C virus (HCV) include blood transfusion, injection drug use, intranasal cocaine use, and body tattoos. We hypothesized that Asian Americans infected with HCV may not identify with these established risk factors present in Caucasians and Hispanics, and our aim was to conduct a survey of risk factors in HCV-infected patients in these ethnic groups. In this prospective study, 494 patients infected with HCV completed a detailed risk assessment questionnaire at a liver centre in Northern California from 2001 to 2008. Among subjects participating in this study, 55% identified themselves as Caucasian, 20% as Hispanic, and 25% as Asian. Asian Americans were older, less likely to smoke or consume alcohol, and have a family history of cancer compared with Caucasians and Hispanics. The laboratory profiles were similar, and genotype 1 was the most common infection in all groups (74-75%). The great majority of Caucasians (94%) and Hispanics (86%) identified with commonly known risk factors, which was in contrast to 67% of Asians (P < 0.0001). The most common risk factors in Asians were blood transfusions (50%) and acupuncture (50%). Furthermore, 74% of Caucasians and 66% of Hispanics identified more than one major risk factor, while only 20% of Asians reported having more than one risk factor (P < 0.0001). Survey for established risk factors for acquisition of HCV may be more appropriate for risk assessment of Caucasians and Hispanics, but not for Asian Americans. These findings may guide the development of HCV screening in our increasingly diverse population.

View details for DOI 10.1111/j.1365-2893.2011.01513.x

View details for Web of Science ID 000299097400014

View details for PubMedID 22239506

Abstract

Lesbian, gay, bisexual, and transgender (LGBT) individuals experience health and health care disparities and have specific health care needs. Medical education organizations have called for LGBT-sensitive training, but how and to what extent schools educate students to deliver comprehensive LGBT patient care is unknown.To characterize LGBT-related medical curricula and associated curricular development practices and to determine deans' assessments of their institutions' LGBT-related curricular content.Deans of medical education (or equivalent) at 176 allopathic or osteopathic medical schools in Canada and the United States were surveyed to complete a 13-question, Web-based questionnaire between May 2009 and March 2010.Reported hours of LGBT-related curricular content.Of 176 schools, 150 (85.2%) responded, and 132 (75.0%) fully completed the questionnaire. The median reported time dedicated to teaching LGBT-related content in the entire curriculum was 5 hours (interquartile range [IQR], 3-8 hours). Of the 132 respondents, 9 (6.8%; 95% CI, 2.5%-11.1%) reported 0 hours taught during preclinical years and 44 (33.3%; 95% CI, 25.3%-41.4%) reported 0 hours during clinical years. Median US allopathic clinical hours were significantly different from US osteopathic clinical hours (2 hours [IQR, 0-4 hours] vs 0 hours [IQR, 0-2 hours]; P = .008). Although 128 of the schools (97.0%; 95% CI, 94.0%-99.9%) taught students to ask patients if they "have sex with men, women, or both" when obtaining a sexual history, the reported teaching frequency of 16 LGBT-specific topic areas in the required curriculum was lower: at least 8 topics at 83 schools (62.9%; 95% CI, 54.6%-71.1%) and all topics at 11 schools (8.3%; 95% CI, 3.6%-13.0%). The institutions' LGBT content was rated as "fair" at 58 schools (43.9%; 95% CI, 35.5%-52.4%). Suggested successful strategies to increase content included curricular material focusing on LGBT-related health and health disparities at 77 schools (58.3%, 95% CI, 49.9%-66.7%) and faculty willing and able to teach LGBT-related curricular content at 67 schools (50.8%, 95% CI, 42.2%-59.3%).The median reported time dedicated to LGBT-related topics in 2009-2010 was small across US and Canadian medical schools, but the quantity, content covered, and perceived quality of instruction varied substantially.

View details for Web of Science ID 000294542600015

View details for PubMedID 21900137

View details for DOI 10.1097/ACM.0b013e31821e4176

View details for Web of Science ID 000292283200011

View details for PubMedID 21715995

Abstract

Previous studies have found ethnicity to be an important predictor of outcomes of treatment with peginterferon (PEG-IFN) and ribavirin (RBV) in chronic hepatitis C. Although the expected sustained virological response (SVR) rates of Hispanics and African Americans are lower than those of Caucasians, SVR rates in Asians appear to be more favorable. However, in some of these studies, hepatitis C virus (HCV) genotype was identified by INNO-LiPA assay, which can mistype the easier-to-treat HCV genotype 6 as genotype 1. Our goal was to compare SVR rates among Caucasian and Asian-American patients with genotype 1 and 2/3 infection whose HCV genotypes were accurately classified by core sequencing testing.A cohort of 269 consecutive treatment-naive HCV-infected patients with genotype 1 or 2/3 (157 Caucasians and 112 Asians) treated with PEG-IFN+RBV from January 2001 to November 2007 at four community-based gastroenterology clinics in Northern California were studied. The analysis of data was by intention-to-treat.The SVR rates for patients with genotype 1 were 45% for Caucasians and 52% for Asians (P=0.37). The SVR rates for patients with genotype 2/3 infection was 77% for Asians and 74% for Caucasians (P=0.7). On multivariate logistic regression analyses adjusting for age, alanine aminotransferase (ALT), baseline viral load, HCV genotype, and treatment adherence, we did not find Asian ethnicity to predict SVR. On a separate analysis, we found that Asians who had HCV genotype 1 or 1b by the less accurate INNO-LiPA assay had significantly higher SVR rates than Caucasians with genotype 1 (64% vs. 45%, respectively, P=0.03).SVR rates were similar in Asian Americans and Caucasians infected with HCV genotype 1 or 2/3 when HCV genotype classification was accurately determined.

View details for DOI 10.1038/ajg.2009.635

View details for Web of Science ID 000277440100019

View details for PubMedID 19904247

Abstract

The results of lamivudine therapy in 4 patients with chemotherapy-induced hepatitis B virus (HBV) reactivation are reported. Cancer chemotherapy-induced reactivation is a known complication in patients with chronic HBV infection or history of HBV infection with recovery. Reactivation of HBV infection has a broad spectrum of manifestations ranging from mild elevation of aminotransferase levels to fatal fulminant hepatitis. Lamivudine is a nucleoside analogue and a potent inhibitor of HBV reverse transcription. The 4 patients treated with lamivudine included 1 woman with breast cancer and 3 men with non-Hodgkin lymphoma, ranging from 41 to 63 years of age. All 4 patients were undergoing standard, multi-agent chemotherapy when they presented with HBV reactivation manifested by sudden onset of fatigue, jaundice, and HBV serology consistent with active HBV infection (detectable serum HBV DNA) in the absence of other known causes of acute hepatitis. Lamivudine therapy (100 mg/d in 3 patients and 150 mg/d in 1 patient) was initiated from 1 to 18 days following the diagnosis of HBV reactivation. All 4 patients showed rapid decrease in aminotransferase levels within 2 weeks after initiating lamivudine therapy. Unfortunately, hepatic synthetic function failed to improve in 2 patients, who both died. The remaining 2 patients had suppression of HBV DNA to undetectable levels after 1 and 4 months of treatment and had biochemical and clinical improvement. The 2 patients who died received lamivudine therapy for 8 days and for 3 weeks. There have been no randomized clinical trials to study the role of lamivudine for prophylaxis or treatment of HBV reactivation associated with chemotherapy. However, based on our limited experience, lamivudine may be efficacious in suppressing potentially fatal HBV reactivation secondary to chemotherapy in patients with chronic HBV infection or prior infection with recovery. Patients who undergo chemotherapy should be screened for the presence of markers of chronic hepatitis B infection or previous HBV infection. We recommend that patients with chronic HBV infection (positive HBV DNA and/or positive HBsAg) or history of HBV infection with recovery (positive hepatitis B core antibody with or without HBsAb) be considered for prophylactic lamivudine use to prevent chemotherapy-induced HBV reactivation.

View details for Web of Science ID 000183597500016

View details for PubMedID 12811213

Abstract

Because of the unique demographics of our patient population, we have had the opportunity to dedicate further studies of the management of hepatitis B and hepatitis C. We have experienced a very low HBV recurrence rate with the use of HBIG in patients transplanted for hepatitis B. Investigations, including the use of new antiviral agents, and the development of approaches to minimize or abrogate disease recurrence such as lower levels of immunosuppression are ongoing. Using a standardized approach to the proper evaluation and selection of patients for liver transplantation with alcoholic liver disease or other liver diseases with coexistent alcohol abuse, we report favorable long-term results in these patients. We have reviewed our results and our approach to the management of EBV and posttransplant lymphoproliferative disorder. There is a firm commitment in our laboratories and outpatient clinics to the investigation of disease prevention, reliable detection and screening methods, and treatment modalities for EBV-related disease. We have addressed specific technical considerations to pediatric liver transplant and have discussed unique aspects of postoperative management in these patients. One-third of the transplants performed at Stanford are in children, 42% of whom are less than one year old. Results with our pediatric transplant recipients compare favorably with those of our adult recipients with patient and graft survival rates approaching 90% at one year and exceeding 80% at 46 months for both groups. As a response to the limited organ supply, we have extended our criteria for suitable donors. Most notably, we have utilized older donors and grafts with significant microsteatosis and have observed good results with these grafts as long as ischemia time is minimized. We have also successfully used reduced size grafts for our pediatric patients with good results and are continuing to expand the use of living-related partial grafts and split allografts.

View details for PubMedID 10503106

Abstract

Pulmonary hypertension, defined as mean pulmonary artery pressure (mPAP) greater than or equal to 25 mmHg, is a recognized complication of hepatic dysfunction with portal hypertension and is considered a relative contraindication to liver transplantation. To characterize pulmonary hemodynamic responses in OLT candidates without pre-existing primary pulmonary hypertension, 22 consecutive patients referred for OLT at the Stanford University Hospital underwent prospective right heart catheterization with pressure determinations at baseline and following infusion of 11 crystalloid over 10 min. In addition, EKG, chest X-ray and transthoracic echocardiograms were performed as a part of the routine evaluation. Eleven non-cirrhotic patients served as controls. At baseline, 1/22 (4.5%) OLT patients had pulmonary hypertension while 9/22 (41%) developed pulmonary hypertension following volume infusion (p < 0.0001). In contrast, 0/11 controls manifested elevated pulmonary pressures at baseline or following volume challenge. OLT candidates were found to have significant increases in mean pulmonary pressure and capillary wedge pressure (PCWP) compared to controls, suggesting intravascular volume overload or left ventricular dysfunction as potential causes. OLT candidates who manifested volume-dependent pulmonary hypertension (a) had a 2-fold higher baseline PCWP, (b) currently smoked, and (c) had previously undergone portosystemic shunts. Aggregate analysis of EKG, echo and CXR for determination of volume-mediated pulmonary hypertension revealed a sensitivity of 25%, specificity of 75% and a positive predictive value of 40%. Preoperative identification of patients with a predisposition to manifesting elevated pulmonary pressures in the context of rapid volume infusion offers the potential for improved risk stratification and optimized clinical management.

View details for Web of Science ID A1996WC09400009

View details for PubMedID 8996773

View details for Web of Science ID A1996TX54100016

View details for PubMedID 8775739

Abstract

Preoperative assessment of orthotopic liver transplantation candidates requires definition of both the anatomy and metabolic function of the native liver. Current evaluation techniques combine computed tomographic scanning, duplex ultrasonography with blood chemistry analysis, and physical stigmata of end-stage liver disease. Recently, magnetic resonance imaging (MRI) has emerged as an alternative method for delineation of hepatic and portal venous anatomy. In addition, MRI accurately measures hepatic volume and portal venous blood flow.To examine the role of MRI-derived indexes of hepatic hemodynamics in the preoperative assessment of liver function, 39 consecutive liver transplantation candidates were studied in a prospective manner. Liver function (aspartate aminotransferase), alanine aminotransferase, alkaline phosphatase, total bilirubin, and albumin levels), hematologic indexes (complete blood cell count, prothrombin time), and Child's classification were determined at the time of evaluation. Axial breath-held multiplanar spoiled-gradient echo MRI measured hepatic volume, whereas a cine phase-contrast sequence perpendicular to the portal vein measured flow.Hepatic index, defined as hepatic mass corrected for body surface area, was found to correlate with prothrombin time (p < 0.04) and platelet count (p < 0.03) by multivariate regression analysis. Portal flow index (PFI), defined as portal flow corrected for hepatic mass), was associated with aspartate aminotransferase (p < 0.02), alanine aminotransferase (p < 0.04), and albumin (p < 0.03) by multivariate regression analysis. In addition, PFI was closely correlated with the patients' functional status as determined by Child's classification system. Increasing values of PFI were associated with declining hepatic functional reserve. Child's class A patients had a mean PFI that was two times less than that of Child's class B patients (0.26 +/- 0.04 versus 0.04 +/- 0.06 ml/min/gm; p < 0.02) and five times less than that of Child's class C patients (0.26 +/- 0.04 versus 1.05 +/- 0.14 ml/min/gm; p < 0.001). Similarly, the mean PFI associated with Child's class B was two times less than that of Child's class C (0.46 +/- 0.06 versus 1.05 +/- 0.14 ml/min/gm; p < 0.01). These data show that MRI-derived indexes of portal hemodynamics and hepatic mass (1) correlate well with biochemical indexes of hepatic dysfunction and (2) serve as anatomic and hemodynamic correlates to Child's functional classification.We conclude that MRI may serve to noninvasively delineate preoperative hepatic vascular anatomy and metabolic dysfunction in candidates undergoing examination for liver transplantation.

View details for Web of Science ID A1995QQ96800003

View details for PubMedID 7716717

Abstract

We sought to determine in a double-blinded, placebo-controlled study if the nonsteroidal anti-inflammatory drug sulindac causes regression of sporadic colonic polyps. The impetus for this study is the profound regressive effect of sulindac on polyps in familial adenomatous polyposis.Asymptomatic patients undergoing routine screening flexible sigmoidoscopy were enrolled if they had polyps of < or = 1 cm in size. Of 162 patients screened, 22 patients were randomly enrolled to take 150 mg of sulindac twice daily, and 22 patients took a placebo. Treatment duration was 4 months and was followed by colonoscopy with removal of all polyps.Four patients were dropped from the study (sulindac group) due to urosepsis (1 patient), heartburn (2 patients), and anemia (1 patient). Compliance (determined by monthly pill counting), mean age, and the effect of sulindac vs. placebo on polyp regression or size were not statistically different in the two treatment groups. Analysis of our data indicated that there is only a 0.8% chance that the probability of polyp regression with sulindac is as large as 50%.Four months of treatment with sulindac does not result in a clinically significant regression of sporadic colonic polyps, although a small effect may not have been detected by the size of our study. Our data suggest that the biological response of sporadic and familial polyposis polyps to sulindac is different.

View details for Web of Science ID A1995QP79200017

View details for PubMedID 7698575

Abstract

With this review we have attempted to highlight key issues in the diagnosis and management of HCV infection in immunocompromised patients. Much of the information is preliminary and will require careful assessment with prospective collection of data in large numbers of patients. With the advent of new assays, our ability to diagnose infection is accurate. We are still lacking sufficient data regarding the natural history of infection to aid substantially in the management of these patients. Finally, we desparately need new therapeutic approaches to this disease. Hopefully, with greater understanding of the replication of this virus and the mechanism of liver pathogenicity, novel approaches to treatment will be developed.

View details for PubMedID 7894966

View details for Web of Science ID A1994NV56300029

View details for PubMedID 8017374

Abstract

Ultrasound (US) of the liver surface with a high-frequency, small-parts, short-focused probe has been proposed as a method of diagnosing cirrhosis. US of the liver was performed in 50 consecutive patients undergoing diagnostic liver biopsy to assess the clinical usefulness of this noninvasive procedure in diagnosing hepatic cirrhosis. Eight patients had histologically proved cirrhosis, and 42 had no histologic evidence of cirrhosis. Seven of the eight patients with cirrhosis had a normal liver surface at US, and five of the 42 patients without cirrhosis had an abnormal liver surface. US of the liver surface with this probe was not reliable in this heterogeneous patient population.

View details for Web of Science ID A1992JN60800005

View details for PubMedID 1523310

View details for Web of Science ID A1992HJ56900020

View details for PubMedID 1595261

Abstract

Although hepatitis C infection has been clearly demonstrated to be transmitted through blood products or blood contamination, most cases of sporadic hepatitis C infection are unassociated with parenteral risk factors, and it is unclear how infection might be acquired by nonparenteral means. One potential mode of nonparenteral transmission is through body secretions. We used a highly sensitive and specific polymerase chain reaction assay to determine whether hepatitis C viral genomic RNA could be detected in secretions obtained from nineteen individuals with chronic hepatitis C virus infection. Although hepatitis C genomic RNA was found in all 19 sera, hepatitis C virus RNA was not detected in any samples of saliva, semen, urine, stool or vaginal secretions from these patients. Viral titers in serum ranged from 10(2) to 10(7) polymerase chain reaction units/ml. The sensitivity of our polymerase chain reaction assay indicates that, if hepatitis C virus were in secretions, it would be present in amounts less than 1 to 4 polymerase chain reaction units/ml. This contrasts with hepatitis B virus infection, in which serum titers frequently are in excess of 10(9) copies of hepatitis B genomes/ml. Body secretions have been found to contain up to 10(6) copies of hepatitis B genomes/ml. Our findings support seroepidemiological studies indicating that nonparenteral transmission of hepatitis C through secretions is uncommon and probably much less efficient than hepatitis B virus infection.

View details for Web of Science ID A1991GN09800003

View details for PubMedID 1657752

View details for Web of Science ID A1990DQ62200023

View details for PubMedID 1697132

Abstract

Study Objective: To determine the efficacy of adenine arabinoside monophosphate (Ara-AMP vidarabine phosphate) with or without human leukocyte interferon in chronic hepatitis B. Study Design: Randomized, double-blinded, placebo-controlled trial with 6-month treatment and an 18-month follow-up. Setting: Referral-based liver-disease clinics at three university medical centers. Patients: Twenty-five patients with chronic active hepatitis or cirrhosis and 39 with chronic persistent hepatitis. Interventions: Thirteen patients received intramuscular Ara-AMP, 2.5 mg/kg body weight, twice daily, alternated monthly for 6 months with subcutaneous human leukocyte interferon, 5 million units, twice daily. Painful paresthesia of the legs necessitated dosage reduction and early discontinuation of enrollment. Twenty-four patients received intramuscular Ara-AMP, 2.5 mg/kg, twice daily, alternated monthly for 6 months with a matching placebo given subcutaneously twice daily. Twenty-seven patients received placebo by intramuscular and subcutaneous injections twice daily for 6 months. Measurements and Main Results: Of the 64 patients, 95% had symptomatic and virologic data available and 64% had biopsies at 12 months; at 24 months, 77% had data available and 56% had repeat biopsies. The highest dropout rate was seen in the group receiving Ara-AMP. The group receiving the placebo was less symptomatic (Karnofsky score of 96% compared with 91% in the group receiving Ara-AMP/placebo and 92% in the group receiving Ara-AMP/human leukocyte interferon, p = 0.02) at 12 but not at 24 months. Loss of DNA polymerase, the hepatitis B e antigen, and the serum hepatitis B virus DNA was similar in all three groups. Histologically, erosion of the limiting plate and lobular activity favored Ara-AMP at 12 but not at 24 months and these differences did not result in differences in the histologic diagnosis. Conclusion: These results do not support the use of Ara-AMP and human leukocyte interferon in chronic persistent or chronic active hepatitis B.

View details for Web of Science ID A1987J946200002

View details for PubMedID 2441633

View details for Web of Science ID A1985AFD8700027

View details for PubMedID 3979964

Abstract

Survival data from 379 patients with chronic hepatitis B were analyzed to determine life expectancy for the patient from the time of first contact. One hundred twenty-one patients had chronic persistent hepatitis, 128 had chronic active hepatitis, and 130 had chronic active hepatitis with cirrhosis. The frequency of symptoms (p less than 0.001), stigmata of chronic liver disease (p less than 0.001), and liver function test abnormalities (p less than 0.001) increased as the histologic features worsened, whereas the percentage of patients with circulating hepatitis B DNA polymerase declined (p less than 0.001). Women were uncommon in our series and had less severe disease than men (p less than 0.02). Fifty-one patients had died by the time of this analysis. The estimated 5-year survival rates were 97% for patients with chronic persistent hepatitis, 86% for those with chronic active hepatitis, and 55% for those with chronic active hepatitis with cirrhosis. The usual cause of death was liver failure and its sequelae. A multivariate analysis found age of 40 years or more, total bilirubin level of 1.5 mg/dL or more, ascites, and spider nevi to be factors that identified patients at a higher risk of death. The prognosis for patients with chronic hepatitis B is similar to that for patients with chronic hepatitis of other causes.

View details for Web of Science ID A1984TR73200006

View details for PubMedID 6486592