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 7837 participants with urinary arsenic metabolite levels 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 participants occurred during an average follow-up period of 19.82years. The data were analyzed using Cox proportional hazards models. Results There was a statistically significant reverse association between inorganic arsenic levels in drinking water and liver cancer showing a hazard ratio (HR) of 0.90 (95% confidence interval [CI]=0.67 to 1.21), 0.66 (95% CI=0.48 to 0.92), and 0.57 (95% CI=0.41 to 0.81) for participants with arsenic levels in the first, second, and third tertile, respectively, compared with those never exposed. A statistically 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 levels in drinking water (≤100.0 μg/L) had the highest risk of developing liver cancer (HR=7.04, 95% CI=4.53 to 10.94) among study groups. Participants with a higher percentage of dimethylarsinic acid had a higher risk of developing hepatitis viral infection–related liver cancer (HR=1.74, 95% CI=1.19 to 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 consistent with previous experimental studies and gives clues for future interventions on hepatitis viral infection–related liver cancer.