Antagonistic effect of arsenic exposure and chronic hepatitis viral infection on hepatocellular carcinoma

Background Arsenic from drinking water causes many health hazards including liver diseases, but the long-term effects of arsenic exposure and methylation capability on hepatitis viral infection related liver cancer remain to be elucidated. Methods This 19-year community-based follow-up study included 7,837 participants with urinary arsenic metabolites level from an arseniasis area in northeastern Taiwan. They were recruited in 1991-1994 and followed up to December 2021. A total of 295 liver cancer cases occurred during an average follow-up period of 19.82 years. The data were analyzed using Cox proportional hazards models. Results There was a significantly reverse association between inorganic arsenic level in drinking water and liver cancer showing a hazard ratio (HR) of 0.90 (95% CI = 0.67-1.21), 0.66 (95% CI = 0.48-0.92), and 0.57 (95% CI = 0.41-0.81) for participants with arsenic level in the first, second, and third tertile, respectively, compared to those never exposed. A significantly monotonic decreasing trend was observed between arsenic exposure levels and hepatitis viral infections related liver cancer. Participants with hepatitis viral infection and low inorganic arsenic level in drinking water (≤100.0 ug/L) had at the highest risk of developing liver cancer (HR = 7.04; 95% CI = 4.53-10.94) among study groups. Participants with a higher DMA% had a higher risk of developing hepatitis viral infection related liver cancer (HR = 1.74; 95% CI = 1.19-2.55) than otherwise. Conclusions This long-term follow-up study demonstrates the suppressive role of inorganic arsenic on hepatitis viral related hepatocellular carcinoma. The finding is coherent to previous experimental studies and gives clues for future interventions on hepatitis viral infection related liver cancer.