Prevention of hepatocellular carcinoma in patients with chronic hepatitis B

Abstract

Patients with chronic hepatitis B are at significant risk for hepatocellular carcinoma (HCC). Globally, over half a million people each year are diagnosed with HCC, with marked geographical variations. Despite overwhelming evidence for a causal role of hepatitis B virus (HBV) infection in the development of HCC and a well-established relationship between high baseline hepatitis B viral load and cumulative risk of HCC, the molecular basis for this association has not been fully elucidated. In addition, a beneficial role for antiviral therapy in preventing the development of HCC has been difficult to establish. This review examines the biological and molecular mechanisms of HBV-related hepatocarcinogenesis, recent results on the effect of modern nucleos(t)ides on the rate of HCC development in high risk HBV cohorts and the potential mechanisms by which long-term antiviral therapy with potent inhibitors of HBV replication might reduce the risk of HCC in patients with chronic hepatitis B. Although evidence from randomized controlled trials shows the favourable effects of antiviral agents in achieving profound and durable suppression of HBV DNA levels while improving liver function and histology, robust evidence of other long-term clinical outcomes, such as prevention of HCC, are limited.

Keywords: Chronic hepatitis B, Entecavir, Hepatitis B virus, Hepatocellular carcinoma, Hepatocarcinogenesis, Nucleoside analogues, Risk reduction

Core tip: There is overwhelming evidence for the causal role of hepatitis B virus (HBV) infection in the development of hepatocellular carcinoma (HCC). However, evidence for the role of antiviral therapy in HCC prevention is inconclusive, in part due to the slow course of HCC development, which makes conducting outcome studies very challenging, while the effectiveness of modern antiviral agents in suppressing HBV means that untreated control group comparisons are ethically unacceptable. We review the impact of HBV treatment on the risk of HCC development, with special focus on emerging data for modern anti-HBV drugs such as entecavir and tenofovir.