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; Hepatocarcinogenesis; Hepatocellular carcinoma; Nucleoside analogues; Risk reduction.

Figure 1

Adjusted hazard ratio for hepatocellular carcinoma by serum hepatitis B virus DNA levels at study entry and last follow-up. Data were adjusted for gender, age, cigarette smoking and alcohol consumption using Cox proportional hazards model. HCC: hepatocellular carcinoma; HBV: Hepatitis B virus. Data sourced from Chen et al[11].

Figure 2

Mechanisms of chronic hepatitis B virus infection-related hepato-carcinogenesis[27-32]. cccDNA: Covalently closed circular DNA. HBV: Hepatitis B virus.