Meta-analysis: the impact of oral anti-viral agents on the incidence of hepatocellular carcinoma in chronic hepatitis B

Aliment Pharmacol Ther. 2013 Jul;38(2):98-106. doi: 10.1111/apt.12344. Epub 2013 May 28.

Abstract

Background: Five oral nucleos(t)ide analogues are available to treat chronic hepatitis B (CHB). With the availability of newer agents, their efficacy on incidence of hepatocellular carcinoma (HCC) is not well described.

Aim: To determine the efficacy of oral anti-viral agents in reducing HCC risk in relationship with other known factors.

Methods: Published studies of at least 20 CHB patients treated with an oral anti-viral agent and followed for >2 years were analysed for incidence of HCC per 100 person years follow-up.

Results: Pooled homogeneous data from six studies showed lamivudine (LAM) treatment (n = 3306) to reduce HCC risk by 51% compared with no treatment (n = 3585) (3.3 vs. 9.7 per 100 person years, P < 0.0001). Pooled data from 49 studies (23 with LAM; 16 with adefovir; and 10 with entecavir, tenofovir or telbivudine) of 10 025 treated patients showed HCC incidence of 1.3 per 100 person years, independent of the agent used. Patient age >50 years and hepatitis B virus-DNA detectability at HCC diagnosis increased risk of HCC by twofold with a 10-fold higher risk among patients with cirrhosis compared with chronic hepatitis. Meta-regression showed patient age, study location (Eastern vs. Western) and type of study (randomised or not) contributed to heterogeneity.

Conclusions: Lamivudine treatment significantly reduces the incidence of HCC compared with no treatment. However, HCC still develops at a rate of 1.3 per 100 patient years in CHB patients receiving an oral anti-viral agent. This finding highlights the need for continued HCC surveillance, particularly in CHB patients with inadequate viral suppression, older age and cirrhosis.

Publication types

  • Meta-Analysis

MeSH terms

  • Adenine / administration & dosage
  • Adenine / analogs & derivatives
  • Adenine / therapeutic use
  • Administration, Oral
  • Age Factors
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / therapeutic use*
  • Carcinoma, Hepatocellular / epidemiology*
  • Carcinoma, Hepatocellular / etiology
  • Guanine / administration & dosage
  • Guanine / analogs & derivatives
  • Guanine / therapeutic use
  • Hepatitis B, Chronic / complications
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Incidence
  • Liver Neoplasms / epidemiology*
  • Liver Neoplasms / etiology
  • Organophosphonates / administration & dosage
  • Organophosphonates / therapeutic use
  • Randomized Controlled Trials as Topic
  • Reverse Transcriptase Inhibitors / administration & dosage
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Telbivudine
  • Tenofovir
  • Thymidine / administration & dosage
  • Thymidine / analogs & derivatives
  • Thymidine / therapeutic use
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Organophosphonates
  • Reverse Transcriptase Inhibitors
  • Telbivudine
  • entecavir
  • Guanine
  • adefovir
  • Tenofovir
  • Adenine
  • Thymidine