HEPATOLOGY WATCH^®

Editorial Board: Emmet B. Keeffe, MD (Chair); M. Eric Gershwin, MD; Ira S. Goldman, MD; John L. Gollan, MD, PhD; Kris V. Kowdley, MD; Paul Martin, MD; Marion G. Peters, MD

JANUARY 2005

CHRONIC HEPATITIS C VIRUS (HCV) INFECTION

Factors affecting HCV clearance and progression to fibrosis. Barbara Piasecki et al. examined the role of alcohol, race, and viral coinfection in the natural clearance of HCV in a retrospective study of 203 spontaneously recovered subjects (anti-HCV+ and HCV RNA-) and 293 patients with chronic HCV (anti-HCV+ and HCV RNA+) identified among a population seen at the Philadelphia Veterans Affairs Medical Center between January 2000 and July 2002. Multivariate analysis showed alcohol use disorder and HIV coinfection to be associated with a reduced clearance of HCV. In contrast, an association between black race and HCV clearance was not statistically significant, and HBV coinfection was found to be a predictor of an increased rate of HCV clearance. These findings indicate that the likelihood of spontaneous clearance of HCV may be affected by alcohol use and viral coinfection, but not race. In a second study, Vincent Di Martino et al. performed a survey of 472 women with chronic HCV infection to examine the influence of estrogen exposure on progression of fibrosis. Among these patients, 157 women completed the survey and had an estimated date of initial HCV infection (96 were postmenopausal, 96 had previous pregnancies, and 105 had used oral contraceptives). Multivariate analysis identified the fibrosis progression rate to be higher in postmenopausal and nulliparous women. Among postmenopausal women, the use of HRT was associated with a lower rate of fibrosis progression. Prior use of oral contraceptives was not found to significantly influence the progression of fibrosis. These results suggest that menopause is associated with a higher rate of fibrosis progression in HCV-infected women and that HRT and previous pregnancies may have a beneficial impact. (Piasecki BA, et al. Hepatology 2004; 40: 892-899 and Di Martino V, et al. Hepatology 2004;40:1426-1433)

Peginterferon alfa-2a plus ribavirin in HCV patients with normal ALT levels. Stefan Zeuzem et al. conducted a multicenter trial in which HCV patients with persistently normal ALT levels were randomized to receive the following treatments: 1) peginterferon alfa-2a 180 ug/week plus ribavirin 800 mg/day for 24 weeks (n = 212); 2) peginterferon alfa-2a plus ribavirin for 48 weeks (n = 210); or 3) no treatment (n = 69). Patients were monitored for 72 weeks. Clearance of HCV RNA did not occur in any patient in the untreated control group. In contrast, sustained virological response (SVR) rates of 30% and 52% were achieved in the 24-week and 48-week combination therapy treatment arms, respectively. Genotype 1-infected patients in the 48-week treatment group had a higher SVR rate compared to those in the 24-week treatment group (40% vs. 13%). The SVR rates for patients with genotype 2 or 3 infection in the 24-week and 48-week treatment groups were similar (72% and 78%). ALT flares were not observed. These findings showed that the results of peginterferon alfa-2a and ribavirin combination therapy in HCV patients with persistently normal ALT levels are similar to those in HCV patients with elevated ALT levels. (Zeuzem S, et al. Gastroenterology 2004;127:1724-1732)

HEPATITIS B VIRUS (HBV) VACCINATION

18-year follow-up of a randomized trial. Man-Fung Yuen and colleagues from the University of Hong Kong tested long-term immunogenicity in 88 subjects who had participated in a HBV vaccine study 18 years earlier. The subjects had been randomized to receive 3 different HBV vaccination regimens: 2-dose recombinant; 3-dose recombinant; and 3-dose plasma-derived vaccines. The two 3-dose vaccine regimen groups had a significantly higher geometric mean titer of anti-HBs and a higher proportion of subjects with anti-HBs titers ≥10 mIU/mL than the 2-dose regimen group. No differences were found between subjects receiving the 3-dose recombinant and the 3-dose plasma-derived vaccine regimens. Anamnestic responses were documented in 70 subjects and no subject became HBsAg(+). Benign breakthrough HBV infection indicated by isolated anti-HBc positivity occurred in 3 patients. These findings showed that the 3-dose regimens were more effective than the 2-dose regimen and that a booster dose was not necessary for up to 18 years after the primary vaccination. (Yuen M-F, et al. Clin Gastroenterol Hepatol 2004;2:941-945)

ACUTE LIVER FAILURE (ALF)

Hypothermia therapy for intracranial hypertension. The encephalopathy of ALF is associated with cerebral edema resulting in increased intracranial pressure (ICP). Treatment options are limited and approximately 30% of patients with ALF and increased ICP die from cerebral herniation while waiting for a suitable liver transplantation donor. Rajiv Jalan and others utilized cooling blankets to reduce the core temperature to 32-33 degrees C in 14 patients with ALF and increased ICP. Hypothermia reduced ICP and significantly decreased arterial ammonia concentration, cerebral blood flow, brain cytokine production, and markers of oxidative stress. With a median of 32 hours of cooling (range, 10-118 hours), 13 patients were successfully maintained until liver transplantation. The transplantation procedures were tolerated without significant complications, and all 13 patients had complete neurological recovery. These data demonstrate that increased ICP can be reduced by hypothermia therapy and further studies are warranted. (Jalan R, et al. Gastroenterology 2004;127:1338-1346)

RECOMMENDED REVIEWS

Polycystic liver disease (PCLD). Autosomal dominant PCLD has been linked to 3 distinct genetic mutations: two are associated with cystic liver and renal disease, and the third mutation results in isolated PCLD. In this review, Gregory Everson et al. describe the natural history, genetics, molecular biology, and management PCLD. (Everson GT, et al. Hepatology 2004;40:774-782)

Hepatitis E. Suzanne Emerson and Robert Purcell provide a global perspective of hepatitis E infection in a brief review in the December 2nd issue of the New England Journal of Medicine. (Emerson SU and Purcell RH. N Engl J Med 2004;351:2367-2368)

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