HEPATOLOGY WATCHTM
Timely Information for Practicing Physicians
APRIL 1998
CHRONIC HEPATITIS C
Chronic hepatitis C and sustained response to interferon-a therapy. Dr. Patrick Marcellin and coworkers assessed the long-term biochemical, virologic, and histologic outcomes in 80 chronic hepatitis C patients who had a sustained response to interferon- a therapy. The 80 patients were followed for a mean of 4.0 years (range, 1-7.6 years) after the end of interferon-a treatment. During the follow-up period serum ALT levels remained normal in 93% of patients, serum HCV RNA remained undetectable in 96% of patients, and liver HCV RNA was undetectable in 27 patients who were tested. These findings indicate that a sustained response to interferon-a therapy in patients with chronic hepatitis C infection is frequently associated with clearance of intrahepatic HCV RNA and marked histologic improvement, suggesting that the viral infection may be eradicated. (Marcellin P, et al. Ann Intern Med 1997; 127: 875-881)
Interferon-a therapy with and without ribavirin for chronic hepatitis C. The Swedish Study Group has investigated the effectiveness and safety of the treatment of patients with chronic hepatitis C virus (HCV) infection with interferon alfa-2b (Intron-A) and the antiviral agent ribavirin (Virazole) compared to interferon alfa-2b alone. One hundred patients were randomized in a double-blind fashion to receive treatment with interferon alfa-2b (3 MU three times a week) in combination with ribavirin (1000-1200 mg per day) or placebo for 24 weeks. Patients were followed for an additional 24 weeks to confirm a sustained virological response. The combination of interferon alfa-2b and ribavirin was associated with a greater percentage of patients achieving a sustained virological response than that observed with interferon therapy alone (36% vs 18%; p=0.047). The authors showed that chronic hepatitis C patients with high HCV RNA loads (>3 million eq/ml) were the subgroup that benefited from concomitant interferon alfa-2b and ribavirin therapy. (Reichard O, et al. Lancet 1998; 351: 83-87)
CHOLESTATIC LIVER DISEASE
Incidence and prevalence of primary biliary cirrhosis. In a recent study, Dr. J.V. Metcalf and colleagues have described the incidence and prevalence of primary biliary cirrhosis in a localized, well-defined population, the city of Newcastle upon Tyne, England. In addition, their case-finding methods included a review of antimitochondrial antibody serum assay databases at the reference immunology laboratory servicing the city’s hospitals. This serologic marker is sensitive and specific for PBC and is included in autoantibody screening for the investigation of many diseases. The diagnostic criteria for PBC were the following: positive antimitochondrial antibody, cholestatic liver function tests, and diagnostic or compatible liver histology. By identifying patients who fulfilled at least two of these three criteria, they found PBC to be more common in Newcastle (prevalence of 240 per million in 1994) than had previously been reported elsewhere in the world. The authors concluded that PBC is more common than is generally believed and that early diagnosis may benefit patients as advances in therapy are made. (Metcalf JV, et al. International Journal of Epidemiology 1997; 26: 830-836)
Transplantation for primary biliary cirrhosis. Primary biliary cirrhosis (PBC) is one of the more common indications for liver transplantation. Dr. James Neuberger reviews the indications for liver transplantation in PBC patients, prognostic models for transplantation, and the subsequent postoperative course of PBC patients undergoing orthotopic liver replacement. Dr. Neuberger reports that recently some clinical centers have reported that a proportion of patients have developed recurrent disease in the allograft. This finding may become important as post-transplant survival increases beyond 10 years. (Neuberger J. Semin Liver Dis 1997; 17: 137-146)
Hepatocellular carcinoma and primary biliary cirrhosis. Dr. David Jones and colleagues determined the incidence and impact on disease outcome of hepatocellular carcinoma (HCC) in a large cohort of 667 patients with primary biliary cirrhosis. HCC was identified in 2.4% of patients with a mean follow-up of 87.7 months (range, 12-246 months). Only those patients with progressive primary biliary cirrhosis (stage III and IV) were observed to develop HCC, and the median survival following the diagnosis of liver cancer was 3 months (range, 1-40 months). Serum alpha-fetoprotein levels were elevated in the majority of HCC patients and Mayo risk scores over-predicted survival in these poor prognostic patients. The authors suggest that early liver transplantation be considered for those patients with advanced primary biliary cirrhosis at high risk for HCC development. (Jones DEJ, et al. Hepatology 1997; 26: 1138 -1142)
Ductular expression of autoantigens in primary biliary cirrhosis. Drs. Ruth Joplin and M. Eric Gershwin review the role of biliary epithelial cell antigens in immune recognition and damage of biliary epithelium in PBC. An important advance has been the identification of a mitochondrial enzyme, pyruvate dehydrogenase dihydrolipoamide acetyltransferase (PDC-E2), as the major autoantigen in PBC. This atypical membrane distribution of PDC-E2 is present in both early and advanced stages of PBC, suggesting an etiologic role as well as a progression of disease role for this antigen. The authors suggest that this research may help uncover the possible importance of biliary epithelial cell membrane antigens in the pathogenesis of PBC. (Joplin R, Gershwin ME. Semin Liver Dis 1997; 17: 97-103)
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