Birth order and risk of hepatocellular carcinoma in chronic carriers of hepatitis B virus: a case-control study in The Gambia

Liver Int. 2015 Oct;35(10):2318-26. doi: 10.1111/liv.12814. Epub 2015 Mar 11.


Background & aims: Early age at infection with Hepatitis B virus (HBV) increases the risk of chronic infection. Moreover, early HBV infection may further independently increase the risk of hepatocellular carcinoma (HCC) beyond its effect on chronicity.

Methods: The distribution of birth order, a proxy for mode and timing of HBV transmission, was compared in The Gambia between hepatitis B surface antigen (HBsAg)-positive HCC cases recruited from hospitals (n = 72) and two HBsAg-positive control groups without HCC: population-based controls from a community HBV screening (n = 392) and hospital-based controls (n = 63).

Results: HCC risk decreased with increasing birth order in the population-based case-control analysis. Using first birth order as the reference, the odds ratios were 0.52 (95% CI: 0.20-1.36), 0.52 (0.17-1.56), 0.57 (0.16-2.05) and 0.14 (0.03-0.64) for second, third, fourth and greater than fourth birth order respectively (P = 0.01). A similar inverse association was observed in the hospital-based case-control comparison (P = 0.04).

Conclusions: Compared to controls, HCC cases had earlier birth order, a proxy for young maternal age and maternal HBV viraemia at birth. This finding suggests that in chronic HBV carriers perinatal mother-to-infant transmission may increase HCC risk more than horizontal transmission. Providing HBV vaccine within 24 h of birth to interrupt perinatal transmission might reduce the incidence of HCC in The Gambia.

Keywords: Africa; Hepatitis B; birth order; carcinoma; hepatocellular; infectious disease transmission; vertical.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Birth Order*
  • Carcinoma, Hepatocellular / epidemiology*
  • Carrier State / epidemiology*
  • Carrier State / virology
  • Case-Control Studies
  • Female
  • Gambia / epidemiology
  • Hepatitis B Surface Antigens / genetics*
  • Hepatitis B Vaccines / therapeutic use
  • Hepatitis B virus
  • Hepatitis B, Chronic / epidemiology*
  • Hepatitis B, Chronic / transmission
  • Humans
  • Infant
  • Infectious Disease Transmission, Vertical
  • Liver Neoplasms / epidemiology*
  • Logistic Models
  • Male
  • Middle Aged
  • Pregnancy
  • Risk Factors


  • Hepatitis B Surface Antigens
  • Hepatitis B Vaccines