Aflatoxin B₁ exposure increases the risk of hepatocellular carcinoma associated with hepatitis C virus infection or alcohol consumption

Background: Hepatocarcinogenicity of aflatoxin B₁ (AFB₁) has rarely been studied in populations with hepatitis C virus (HCV) infection and those without hepatitis B virus (HBV) and HCV infection (non-B-non-C). This case-control study nested in a community-based cohort aimed to investigate the HCC risk associated with AFB₁ in HCV-infected and non-B-non-C participants. Methods: Baseline serum AFB₁-albumin adduct levels were measured in 100 HCC cases and 1767 controls seronegative for anti-HCV and HBsAg (non-B-non-C), and another 103 HCC cases and 176 controls who were anti-HCV-seropositive and HBsAg-seronegative. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using logistic regression. Results: In 20 years of follow-up, the follow-up time to newly developed HCC was significantly shorter in participants with higher serum AFB₁-albumin adduct levels in non-B-non-C (p = 0.0162) and HCV-infected participants (p < 0.0001). Within 8 years of follow-up, HCV infection and AFB₁ exposure were independent risk factors for HCC. Elevated serum AFB₁-albumin adduct levels were significantly associated with an increased risk of HCC newly developed within 8 years of follow-up in non-B-non-C participants with habitual alcohol consumption [crude OR (95% CI) for high vs. low/undetectable levels, 4.22 (1.16–15.37)] and HCV-infected participants [3.39 (1.31–8.77)], but not in non-B-non-C participants without alcohol drinking habit. AFB₁ exposure remained an independent risk predictor for HCV-related HCC after adjustment for other HCC predictors (multivariate-adjusted OR [95% CI], 3.65 [1.32–10.10]). Conclusions: AFB₁ exposure contributes to the development of HCC in participants with significant risk factors for cirrhosis including alcohol and HCV infection.