A meta-analysis on the risk of hepatocellular carcinoma (HCC) among hepatitis B virus (HBV) genotypes is warranted as the current data are conflicting.


To investigate the relative risk of HCC among the four major HBV genotypes (A–D).


A meta-analysis was performed based on literature search from electronic databases and bibliography between 1950 and 2012. All abstracts with keywords ‘hepatitis B’, ‘hepatocellular carcinoma’ and ‘genotype’ were screened. Studies were included if they reported HBV genotype as an exposure and HCC as an outcome.


Nine hundred and eighty-eight abstracts were found through literature search, among them 43 studies were eligible for this meta-analysis. A total of 14 545 patients with an average age of 43 years were included; 71% were male patients and 17% had cirrhosis. In 33 studies, HCC was found in 1541/6060 (25%) genotype C vs. 550/4417 (12%) genotype B HBV-infected patients [odds ratio (OR) = 2.05, 95% confidence interval (CI) = 1.52–2.76, P < 0.001]. No difference in the risk of HCC was found among genotype A (71/517, 14%) vs. genotype D (170/1506, 11%) HBV-infected patients in 14 studies (OR = 0.94, 95% CI = 0.67–1.32). In 10 studies, the risk of HCC was also found higher among genotype C (498/1659, 30%) than genotype A&D (103/1403, 7%) HBV-infected patients (OR = 2.34, 95% CI = 1.63–3.34, P < 0.001). Subgenotype Ce and Cs HBV-infected patients had similar risk on HCC (OR = 1.13, 95% CI = 0.76–1.67, P = 0.54). On funnel plot analysis, there was no significant publication bias in all comparisons.


Genotype C hepatitis B virus is associated with a higher risk of hepatocellular carcinoma than other major hepatitis B virus genotypes.