Hepatitis: Bass NM

Kadayifci A, Merriman RB, Bass NM. · Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143-0538, USA. · Clin Liver Dis. · Pubmed #17544975 No free full text.

Abstract: There is no proven medical treatment of non-alcoholic steatohepatitis (NASH). Most prior therapeutic trials have had methodologic limitations. Insulin sensitizers are the more promising therapeutic candidates among categories that include antioxidants, lipid-lowering agents, and antiobesity drugs. The future will see the evaluation of novel agents and a comprehensive treatment strategy that addresses the risk factors for the metabolic syndrome. This article reviews the current status of medical management options for NASH.

Davern TJ, Bass NM. · University of California, Division of Gastroenterology, 513 Parnassus Avenue, Room S-357, San Francisco 94143, CA, USA. · Clin Liver Dis. · Pubmed #12879996 No free full text.

Abstract: Hepatotoxicity is the most common cause of fulminant hepatic failure in the United States and the main indication for market withdrawal of drugs. This condition has been increasingly recognized as a problem of enormous medical, financial legal, and regulatory importance. It is in context of this heightened awareness of hepatotoxicity, particularly associated with new high profile drugs, that the authors reviews the published data regarding liver injury related to a novel group of asthma drugs.

Yao FY, Bass NM. · Department of Transplantation, California Pacific Medical Center, San Francisco 94143-0538, USA. · J Hepatol. · Pubmed #10952248 No free full text.

Abstract: BACKGROUND/AIMS: Lamivudine is highly effective in suppressing hepatitis B viral replication and hepatic necroinflammatory activity. The potential for recovery of hepatic decompensation in patients with chronic hepatitis B infection treated with lamivudine has not been established. The aim of this study was to evaluate the effectiveness of lamivudine treatment in severely decompensated cirrhosis due to chronic hepatitis B. METHODS: Thirteen consecutive patients with chronic hepatitis B infection, Child's-Pugh-Turcotte (CPT) score of > or =10 (median score=11) and detectable circulating hepatitis B DNA (range 15 to 9634 pg/ml) were included and treated with lamivudine 150 mg once daily. Hepatitis B envelope antigen (HBeAg) was positive in 9 of 13 patients pre-treatment. RESULTS: Two patients underwent liver transplantation at 4 and 6 weeks after starting lamivudine treatment. The remaining 11 patients were followed for a mean of 17.5 months without liver transplantation (range 3 to 39 months). Significant improvement of liver function, defined as a decrease in CPT score of > or =3, was observed in 9 of 13 patients (69%). In five patients, CPT score improved to <7 and they were placed on the inactive status (UNOS status 7) for liver transplantation. Hepatitis B DNA remained negative in all except one patient who developed breakthrough viral replication 12 months after starting lamivudine treatment, while maintaining stable liver function. Three of seven HBeAg-positive patients who did not undergo liver transplantation lost HBeAg during follow-up, but none had sustained seroconversion to hepatitis B e antibody. CONCLUSION: Lamivudine appears highly effective in reversing severe hepatic decompensation due to replicating hepatitis B infection.

Bahl M, Qayyum A, Westphalen AC, Noworolski SM, Chu PW, Ferrell L, Tien PC, Bass NM, Merriman RB. · Department of Radiology, University of California, San Francisco, Box 0628, L-307, 505 Parnassus Ave, San Francisco, CA 94143-0628, USA. · Radiology. · Pubmed #18796674 No free full text.

Abstract: PURPOSE: To investigate if opposed-phase T1-weighted and fat-suppressed T2-weighted liver signal intensity (SI) loss and visceral fat measurement at magnetic resonance (MR) imaging and body mass index (BMI) are correlated with grade of liver steatosis in patients with nonalcoholic fatty liver disease (NAFLD) or hepatitis C virus (HCV) and human immunodeficiency virus (HIV)-related liver disease. MATERIALS AND METHODS: Committee on Human Research approval and patient consent were obtained for this HIPAA-compliant study. Fifty-two patients (15 men, 37 women) with NAFLD (n = 29) or HCV and HIV-related liver disease (n = 23) underwent prospective contemporaneous MR imaging and liver biopsy. Liver SI loss was measured on opposed-phase T1-weighted and fat-suppressed T2-weighted MR images. Visceral fat area was measured at three levels on water-suppressed T1-weighted MR images (n = 44). Spearman rank correlation coefficients and recursive partitioning were used to examine correlations. RESULTS: Histopathologic liver steatosis correlated well with liver SI loss on opposed-phase T1-weighted MR images (rho = 0.78), fat-suppressed T2-weighted MR images (rho = 0.75), and average visceral fat area (rho = 0.77) (all P < .01) but poorly with BMI (rho = 0.53, P < .01). Liver SI losses on opposed-phase T1-weighted MR imaging of less than 3%, at least 3% but less than 35%, at least 35% but less than 49%, and at least 49% corresponded to histopathologic steatosis grades of 0 (n = 16 of 17), 1 (n = 11 of 16), 2 (n = 7 of 13), and 3 (n = 5 of 6), respectively. A visceral fat area of greater than or equal to 73.8 cm(2) was associated with the presence of histopathologic steatosis in 41 of 44 patients. CONCLUSION: Liver SI loss on opposed-phase T1-weighted MR images and visceral fat area may be used as biomarkers for the presence of liver steatosis and appear to be superior to BMI.

Patel D, Terrault NA, Yao FY, Bass NM, Ladabaum U. · Division of Gastroenterology, Department of Medicine, University of California, 513 Parnassus Avenue, San Francisco, CA 94143-0538, USA. · Clin Gastroenterol Hepatol. · Pubmed #15645408 No free full text.

Abstract: BACKGROUND & AIMS: HCV-related cirrhosis is a leading risk factor for hepatocellular carcinoma (HCC). Surveillance might detect HCC at a treatable stage. We estimated the clinical and economic consequences of a common HCC surveillance strategy in patients with HCV-related cirrhosis in the context of alternative HCC treatment strategies. METHODS: With a Markov model, we examined surveillance with serum alpha-fetoprotein and ultrasound every 6 months in patients with compensated HCV-related cirrhosis from age 45-70 years or death, and HCC treatment with resection, cadaveric liver transplantation (CLT), or living donor liver transplantation (LDLT). RESULTS: Compared to natural history in the base case, surveillance with resection, listing for CLT, or LDLT increased life expectancy by 0.49, 2.58, and 3.81 quality-adjusted life-years (QALYs), respectively, all at costs less than 51,000 US dollars/QALY gained. The consequences of surveillance were most sensitive to the outcomes and costs of HCC treatments but not surveillance test performance characteristics or cost. Prioritizing CLT for patients with HCC over those with decompensated cirrhosis resulted in greater overall life expectancy with minimal increase in cost. CONCLUSIONS: Surveillance for HCC in patients with compensated HCV-related cirrhosis might gain QALYs at acceptable costs. The impact of surveillance depends most on the outcomes and costs of HCC treatments, rather than surveillance test characteristics. By increasing organ availability for timely definitive treatment, LDLT might achieve the greatest gain in life expectancy at acceptable costs. Prioritizing CLT for HCC might increase the population-wide benefits of CLT.

Yao FY, Saab S, Bass NM, Hirose R, Ly D, Terrault N, Lazar AA, Bacchetti P, Ascher NL, Roberts JP. · Department of Medicine University of California, San Francisco, San Francisco, CA, USA. · Hepatology. · Pubmed #14752842 No free full text.

Abstract: The current policy for determining priority for organ allocation is based on the model for end stage liver disease (MELD). We hypothesize that severity of graft dysfunction assessed by either the MELD score or the Child-Turcotte-Pugh (CTP) score correlates with mortality after liver retransplantation (re-OLT). To test this hypothesis, we analyzed the outcome of 40 consecutive patients who received re-OLT more than 90 days after primary orthotopic liver transplantation (OLT). The Kaplan-Meier 1-year and 5-year survival rates after re-OLT were 69% and 62%, respectively. The area under the curve (AUC) values generated by the receiver operating characteristics (ROC) curves were 0.82 (CI 0.70-0.94) and 0.68 (CI 0.49-0.86), respectively (P =.11), for the CTP and MELD models in predicting 1-year mortality after re-OLT. The 1-year and 5-year survival rates for patients with CTP scores less than 10 were 100% versus 50% and 40%, respectively, for CTP scores of at least 10 (P =.0006). Patients with MELD scores less than or equal to 25 had 1-year and 5-year survival rates of 89% and 79%, respectively, versus 53% and 47%, respectively, for MELD scores greater than 25 (P =.038). Other mortality predictors include hepatic encephalopathy, intensive care unit (ICU) stay, recurrent hepatitis C virus (HCV) infection, and creatinine level of 2 mg/dL or higher. Analysis of an independent cohort of 49 patients showed a trend for a correlation between CTP and MELD scores with 1-year mortality, with AUC of 0.59 and 0.57, in respective ROC curves. In conclusion, our results suggest that severity of graft failure based on CTP and MELD scores may be associated with worse outcome after re-OLT and provide a cautionary note for the "sickest first" policy of organ allocation.

Yao FY, Terrault NA, Freise C, Maslow L, Bass NM. · Department of Medicine, Division of Gastroenterology, University of California, San Francisco, CA 94143-0538, USA. · Hepatology. · Pubmed #11481627 No free full text.

Abstract: Uncontrolled studies have suggested a beneficial effect of lamivudine in patients with decompensated cirrhosis caused by replicating hepatitis B virus (HBV). We analyzed the outcome of lamivudine treatment in 23 consecutive patients with severely decompensated HBV-cirrhosis defined as a Child-Pugh-Turcotte (CPT) score of > or =10, and compared with a historical untreated control group of 23 patients matched for age, gender, and baseline CPT score. Significant clinical response, defined as a decrease in the CPT score by > or =3 points, was observed in 14 of 23 (60.9%) treated patients versus none of the controls (P <.0001). The median change in CPT scores was -3.0 (range, -6 to +3) in the treated group versus +1.0 in the controls (range, -1 to +2) (P =.016). Orthotopic liver transplantation (OLT) was performed in 34.8% of treated patients (median, 3.5; range, 1-32 months), versus 73.9% of controls (median, 3.0; range, 1-14 months) (P =.04). Excluding transplanted patients, there were no deaths in the treated group versus 6 deaths in the control group (P =.009). Time to death or OLT was significantly longer in treated patients than in controls (P <.001). Two patients developed lamivudine resistance after 9 and 12 months, respectively. Our results suggest that lamivudine significantly improves hepatic function in over half of the patients with decompensated cirrhosis and replicating HBV, and may confer a survival advantage. However, the small sample size and the use of a retrospective control cohort preclude drawing definitive conclusions. Expedited OLT remains the only viable treatment for lamivudine nonresponders.

Reinus JF, Persky S, Burkiewicz JS, Quan D, Bass NM, Davern TJ. · Division of Gastroenterology and Hepatology, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467, USA. · Ann Intern Med. · Pubmed #11119397 links to  free full text

Abstract: BACKGROUND: In registration trials, zafirlukast, an asthma medication, caused asymptomatic elevated aminotransferase levels in up to 5% of participants. Until now, however, no cases of severe hepatitis attributed to zafirlukast have been reported. OBJECTIVE: To report the clinical characteristics of three patients with severe hepatitis due to zafirlukast. DESIGN: Case report. SETTING: One community hospital and two university hospitals. PATIENTS: Three middle-aged women taking zafirlukast, 20 mg twice per day. INTERVENTION: Discontinuation of zafirlukast therapy in three patients, steroid therapy in two patients, and orthotopic liver transplantation in one patient. MEASUREMENTS: Serum aminotransferase and bilirubin levels, standard blood tests for causes of hepatitis other than drug toxicity, and liver biopsy in two patients. RESULTS: Patient 1 recovered spontaneously, had a severe relapse after inadvertent rechallenge with the medication, and ultimately made a complete recovery. Patient 2 developed subfulminant hepatic failure and required liver transplantation. Patient 3 developed severe hepatitis that improved after treatment with corticosteroids. Liver tissue was available from two patients and showed histologic changes commonly associated with drug reactions. CONCLUSION: Patients receiving zafirlukast may develop severe liver injury and should be observed for signs and symptoms of hepatitis.

Bass NM. · Department of Medicine University of California, San Francisco San Francisco, CA, USA. · Hepatology. · Pubmed #9918944 No free full text.

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