Metals exposure and biomarkers of liver damage: a systematic review and meta-analysis of observational studies

Introduction: Environmental exposure to metals represents a significant global health concern, yet the hepatotoxic potential of these contaminants remains incompletely characterized. This systematic review and meta-analysis aimed to quantify the association between exposure to metals and liver damage as indicated by liver enzyme alterations. Content: We conducted a comprehensive search of electronic databases for epidemiological studies that examined associations between metal exposure and liver enzymes. Using random-effects models, we calculated pooled standardized mean differences (SMDs) with 95 % confidence intervals (CIs) for each metal. Subgroup analyses explored variations by geographical region, exposure assessment methodology, liver biomarkers, and study characteristics. Summary: Thirty-nine studies met inclusion criteria. All four metals showed significant positive associations with liver damage, with cadmium exhibiting the strongest association (SMD=5.98, 95 % CI: 2.16–9.87), followed by lead (SMD=5.48, 95 % CI: 0.63–10.33), mercury (SMD=5.15, 95 % CI: 0.21–10.51), and arsenic (SMD=1.52, 95 % CI: 0.53–2.52). Metal-specific patterns of liver enzyme alterations were observed: arsenic primarily affected transaminases (ALT, AST), while cadmium, mercury, and lead showed stronger associations with AST and GGT. Outlook: This systematic review and meta-analysis provides robust evidence that environmental exposure to arsenic, cadmium, mercury, and lead is significantly associated with liver damage across diverse populations.