Hepatocellular carcinoma (HCC) incidence is high in The Gambia, and hepatitis B virus (HBV)
infection is the main cause. People coinfected with HBV and hepatitis D virus (HDV) have an even greater risk of HCC and
cirrhosis. Using a new HDV quantitative microarray antibody capture (Q-MAC) assay, we evaluated the association between HDV
infection and HCC or
cirrhosis among participants in The Gambia
Liver Cancer Study. In this case-control study, cases had HCC (n = 312) or
cirrhosis (n = 119). Controls (n = 470) had no clinical evidence of
liver disease and normal serum alpha-foetoprotein. Participants were previously tested for
hepatitis B surface antigen (
HBsAg); we tested HBsAg+ specimens by HDV Q-MAC, western blot and
RNA assays. We evaluated separate cut-offs of the Q-MAC assay for predicting anti-HDV and
RNA positivity. Q-MAC correctly identified 29/29 subjects who were western blot-positive (sensitivity = 100%, specificity = 99.4%) and 16/17 who were
RNA-positive (sensitivity = 94.1%, specificity = 100%). Compared to controls, cases more often had HBV monoinfection (
HBsAg+/HDV
RNA-; 54.1% vs 17.0%; odds ratio [OR] = 6.28; P < 0.001) or HBV-HDV
coinfection (
HBsAg+/HDV
RNA+; 3.9% vs 0%; P < 0.001). Risk estimates (for HCC or
cirrhosis) based on HDV antibody status and adjusted for covariates (demographics, alcohol, smoking, body mass index, anti-HCV and
aflatoxin B1 exposure) yielded consistent results for both HBV monoinfection (adjusted OR = 8.29; 95% confidence interval = 5.74-11.98) and HBV-HDV
coinfection (adjusted OR = 30.66; 95% confidence interval = 6.97-134.95). In this Gambian population, HDV Q-MAC had high sensitivity and specificity for both anti-HDV and HDV
RNA. HDV
infection contributed to the high risk of HCC in The Gambia.