Hepatitis B virus infection increases the risk of cholangiocarcinoma: a meta-analysis and systematic review

J Gastroenterol Hepatol. 2012 Oct;27(10):1561-8. doi: 10.1111/j.1440-1746.2012.07207.x.


Background and aim: A number of studies have shown that hepatitis virus infections may be associated with cholangiocarcinoma (CC). However, the relationship between hepatitis B virus (HBV) infection and CC, especially intrahepatic cholangiocarcinoma (ICC), is still controversial.

Methods: Relevant studies were identified by searching PUBMED, EMBASE and Web of Science Datebases up to September 2011. Pooled risk estimates were calculated using a random-effects model. Potential sources of heterogeneity were performed by subgroup analyses. A total of 18 papers were included in this meta-analysis.

Results: The pooled risk estimate of all studies showed a statistically significant increased risk of CC among individuals with HBV infection (rate ratio [RR]: 2.66; 95% confidence interval [CI]: 1.97, 3.60). Compared with those without HBV infection, persons with HBV infection had an increased risk of intra-CC (ICC) (RR: 3.42; 95% CI: 2.46, 43.74), extrahepatic CC (OR: 1.46; 95% CI: 0.98, 2.17), and CC (OR: 2.03; 95% CI: 1.15, 3.56). In a subgroup analysis of HBV infection and risk of ICC, the pooled risk estimate of studies in Asians (RR: 3.63; 95% CI: 2.56, 5.13) was higher than that in non-Asians (RR: 1.93; 95% CI: 0.78, 4.76). A Begg funnel plot and Egger test revealed no evidence for publication bias.

Conclusions: This meta-analysis shows that HBV is associated with increased risk of CC, especially for ICC. Further investigation is needed to focus on the mechanism by which HBV may be involved in the pathogenesis of CC.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Asia / epidemiology
  • Asian People
  • Bile Duct Neoplasms / epidemiology*
  • Bile Duct Neoplasms / ethnology
  • Bile Duct Neoplasms / virology
  • Bile Ducts, Intrahepatic* / virology
  • Cholangiocarcinoma / epidemiology*
  • Cholangiocarcinoma / ethnology
  • Cholangiocarcinoma / virology
  • Female
  • Hepatitis B / epidemiology*
  • Hepatitis B / ethnology
  • Hepatitis B / virology
  • Humans
  • Liver Neoplasms / epidemiology*
  • Liver Neoplasms / ethnology
  • Liver Neoplasms / virology
  • Male
  • Middle Aged
  • Odds Ratio
  • Risk Assessment
  • Risk Factors