Hepatitis B virus mutation may play a role in hepatocellular carcinoma recurrence: A systematic review and meta-regression analysis

J Gastroenterol Hepatol. 2015 Jun;30(6):977-83. doi: 10.1111/jgh.12917.

Abstract

Background and aims: A number of studies have confirmed that antiviral therapy with nucleotide analogs (NAs) can improve the prognosis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative therapy. However, what factors affected the prognosis of HBV-HCC after removal of the primary tumor and inhibition of HBV replication? A meta-regression analysis was conducted to explore the prognostic factor for this subgroup of patients.

Methods: MEDLINE, EMBASE, Web of Science, and Cochrane library were searched from January 1995 to February 2014 for clinical trials evaluating the effect of NAs on the prognosis of HBV-HCC after curative therapy. Data were extracted for host, viral, and intervention information. Single-arm meta-analysis was performed to assess overall survival (OS) rates and HCC recurrence. Meta-regression analysis was carried out to explore risk factors for 1-year OS rate and HCC recurrence for HBV-HCC patients after curative therapy and antiviral therapy.

Results: Fourteen observational studies with 1284 patients met the inclusion criteria. Influential factors for prognosis of HCC were mainly baseline HBeAg positivity, cirrhotic stage, advanced Tumor-Node-Metastasis (TNM) stage, macrovascular invasion, and antiviral agent type. The 1-year OS rate decreased by more than four times (coefficient -4.45, P<0.001) and the 1-year HCC recurrence increased by more than one time (coefficient 1.20, P=0.003) when lamivudine was chosen for HCC after curative therapy, relative to entecavir for HCC.

Conclusions: HBV mutation may play a role in HCC recurrence. Entecavir or tenofovir, a high genetic barrier to resistance, should be recommended for HBV-HCC patients.

Keywords: HBV; hepatocellular carcinoma; nucleotide analogs.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antiviral Agents / therapeutic use
  • Carcinoma, Hepatocellular / etiology*
  • Carcinoma, Hepatocellular / therapy*
  • Combined Modality Therapy
  • Databases, Bibliographic
  • Female
  • Guanine / analogs & derivatives
  • Guanine / therapeutic use
  • Hepatitis B / complications
  • Hepatitis B / drug therapy
  • Hepatitis B / virology*
  • Hepatitis B virus / genetics*
  • Humans
  • Liver Neoplasms / etiology*
  • Liver Neoplasms / therapy*
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Neoplasm Recurrence, Local
  • Prognosis
  • Regression Analysis
  • Tenofovir / therapeutic use

Substances

  • Antiviral Agents
  • entecavir
  • Guanine
  • Tenofovir