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

Abstract

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.