Aflatoxin B1 Exposure and Hepatocellular Carcinoma in South America: A Multinational Cross-Sectional Analysis.

Aflatoxin B1 (AFB1), a dietary mycotoxin classified as a Group 1 carcinogen and a risk factor for hepatocellular carcinoma (HCC), has seen limited biomarker-based evidence linking it to HCC in South America despite favorable regional contamination conditions. Utilizing a newly validated isotope-dilution HPLC-MS/MS method to quantify AFB1-Lysine (AFB1-Lys) adducts, we conducted a cross-sectional study involving 92 HCC patients and 70 healthy controls across six South American nations. The primary case-control analysis, focusing on 64 HCC patients and 70 controls from Argentina and Colombia, revealed that AFB1-Lys concentrations and positivity rates were significantly higher in HCC cases compared to controls (7.16 vs. 0.89 pg/mg albumin; 43% vs. 10%). Multivariable logistic regression demonstrated that detectable AFB1-Lys was significantly and independently associated with HCC (adjusted OR = 3.72), with associations most pronounced, though based on small subgroups, in viral hepatitis-related and cryptogenic HCC. Furthermore, broader regional analysis indicated higher AFB1-Lys positivity rates in HBV-positive patients than in HCV-positive or non-viral HCC cases. Ultimately, chronic dietary aflatoxin exposure shows a consistent, statistically significant association with hepatocarcinogenesis across diverse etiological backgrounds in South America, highlighting an urgent need for integrated regional food safety surveillance and expanded prospective studies.