Association between Hepatitis B Surface Antigen Levels and the Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Infection: Systematic Review and Meta-Analysis

Document Type : Systematic Review and Meta-analysis


1 Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Thailand.

2 Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Thailand.

3 Centre of Excellence in Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University, Thailand.


Background: The role of hepatitis B surface antigen (HBsAg) levels in predicting the risk of developing
hepatocellular carcinoma (HCC) has remained unclear. The aim of this study was to obtain the most up-to-date estimated
measure of the association between HBsAg levels and the development of HCC in patients. Methods: We performed a
systematic review by searching for relevant studies on PubMed, Scopus, ProQuest and the Cochrane Central Register
of Controlled Trials from January 2002 to November 2017. We presented the effects of HBsAg levels at each cut-off
value as the odds ratios (ORs) at 95% confidence interval (CI). We also investigated HCC and its potential risk factors
including HBeAg, and HBV DNA. We registered our protocol with the International Prospective Register of Systematic
Reviews (PROSPERO) with the registration number CRD42018081138. Results: We selected 10 studies representing
12 541 cases. At the 100 IU/ml cut-off, the OR for HCC at the high HBsAg level versus the low level was 4.99 (95%
CI, 3.01–8.29) with high inconsistency (I2=79%). At the 1,000 IU/ml threshold, the pooled OR for HCC at the high
HBsAg versus the low level was 2.46 (95% CI, 2.15–2.83) with low variance. We also found correlations between the
risk of HCC and male gender (OR=2.12), hepatitis B e-antigen positivity (OR=2.99), or hepatitis B (HBV) viral load
≥ 2,000 IU/ml (OR=4.37). Conclusion: Our study revealed that HBsAg levels ≥ 100 IU/ml, and notably >1,000 IU/
ml, are associated with an increased risk of HCC development.


Main Subjects

Volume 20, Issue 8
August 2019
Pages 2239-2246
  • Receive Date: 15 June 2019
  • Revise Date: 30 July 2019
  • Accept Date: 12 August 2019
  • First Publish Date: 12 August 2019