Association between occult hepatitis B infection and the risk of hepatocellular carcinoma: a meta-analysis

Liver Int. 2012 Feb;32(2):231-40. doi: 10.1111/j.1478-3231.2011.02481.x. Epub 2011 Feb 23.


Background: The association between occult hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) remains controversial.

Aims: We conducted a meta-analysis of prospective studies and retrospective studies to examine whether occult HBV infection increases the risk of HCC.

Methods: Two independent reviewers searched databases for eligible studies published in English or Chinese dated from 1966 to 6 April 2010. The odds ratios or the relative risks (RRs) of each study were considered respectively.

Results: We identified 16 eligible studies. A significantly increased risk of HCC was found in subjects with occult HBV infection in comparison with non-infected controls in both retrospective [OR(unadjusted) =6.08, 95% confidence interval (CI)=3.45-10.72] and prospective studies (RR(adjusted) =2.86, 95% CI=1.59-4.13), and occult HBV increased the risk for HCC in both hepatitis C virus (HCV)-infected populations (summary RR=2.83, 95% CI=1.56-4.10) and in non-infected populations (OR(unadjusted) =10.65, 95% CI=5.94-19.08). A higher prevalence of occult HBV was observed in individuals who were positive for anti-HBs and anti-HBc (OR(unadjusted) =1.81, 95% CI=1.06, 3.09).

Conclusion: Our findings suggest that occult HBV infection was associated with an increased risk of HCC. Occult HBV may serve as a cofactor in the development of HCV-related HCC, and it may also play a direct role in promoting Non-B and Non-C HCC growth. Suggestive evidence indicates that individuals with a concomitant presence of anti-HBs and anti-HBc had an increased risk of occult HBV infection. However, further studies are needed to clarify these observations.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / epidemiology
  • Carcinoma, Hepatocellular / virology*
  • Comorbidity
  • Databases, Bibliographic
  • Female
  • Hepacivirus / immunology
  • Hepacivirus / isolation & purification
  • Hepatitis B Antigens / immunology
  • Hepatitis B virus / immunology
  • Hepatitis B virus / isolation & purification
  • Hepatitis B, Chronic / complications*
  • Hepatitis B, Chronic / diagnosis
  • Hepatitis B, Chronic / epidemiology
  • Humans
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / virology*
  • Male
  • Prospective Studies
  • Retrospective Studies
  • Risk Assessment


  • Hepatitis B Antigens