Overview

• In a retrospective analysis of 551 patients who received chemotherapy before liver resection, the PNPLA3 gene variant was strongly associated with chemotherapy-associated liver injury.
• All patients homozygous for the PNPLA3 I148M (rs738409) variant showed significant liver injury after chemotherapy, and higher injury scores correlated with worse overall survival.
• Researchers used APRI plus ALBI scoring to track liver function during treatment, with homozygous carriers consistently classified as high risk.
• Variant prevalence varies widely by population—over 41% in Japan, over 71% in people of Peruvian descent, and under 10% in some European groups—offering a potential explanation for inconsistent international trial results.
• Authors propose blood testing for the variant and closer liver monitoring to tailor chemotherapy timing or allow recovery before surgery, noting the study is observational and requires prospective validation.