Abstract IA37: Prevention of Hepatocellular Carcinoma (HCC) with antiviral therapy

Abstract

Abstract On a world-wide basis, chronic viral hepatitis accounts for nearly 75% of all cases of HCC. One of the important implications of this is that HCC may be more readily preventable either by vaccination or with anti-viral therapy. Antiviral therapy against hepatitis B has largely evolved away from using alpha interferon to nucleoside analogues. Lamivudine is the nucleoside analogue agent that has been best studied in preventing HCC. In a large prospective, randomized placebo-controlled trial of lamivudine therapy in patients with advanced liver disease associated with HBV infection, 3.9% of patients receiving lamivudine developed HCC compared to 7.4% on placebo (p=0.047) (1). More recently entecavir and tenofovir have become widely used as the main antiviral agents to control HBV infection. Both agents appear to be very effective in controlling HBV infection but data on their ability to reduce the risk of HCC are controversial. At least two meta-analyses have been done of the anti-cancer benefits of antiviral therapy. Chronic HCV infection appears to be associated with about 30% of HCCs worldwide but in some regions including Europe and the United States it is the leading underlying cause of HCC. The evidence is substantial that effective treatment of hepatitis C can reduce the risk of HCC. The HALT-C Trial was a large randomized controlled trial carried out at multiple sites within the United States, enrolling more than 1,000 patients and randomized patients with HCV infection and advanced fibrosis (bridging hepatic fibrosis or cirrhosis) to receive long-term maintenance therapy with a low dose of peginterferon alfa or to remain untreated for a period of 4 years (2). The initial report from this study showed that antiviral therapy did not reduce the rate of either hepatic decompensation or HCC but an analysis of liver related outcomes after 7 to 8 years of follow up among patients who did not respond to therapy colleagues found that patients who achieved viral cure had significantly lower rates of hepatic decompensation, liver transplantation, or HCC than patients with remained non-responders to interferon (3). This was confirmed in other large cohort studies from several countries in Europe and Canada and meta-analyses. In summary, antiviral treatment for viral hepatitis appears to have benefits in decreasing the risk of HCC in chronically infected patients. This benefit is most pronounced in patients with chronic hepatitis C and advanced hepatic fibrosis or cirrhosis in patients achieving viral clearance and seems much more marginal in patients with chronic hepatitis B where antiviral therapy usually results in viral suppression rather than elimination.