Human Health Effects of Chronic Microcystin Exposure: A Systematic Review and Meta-Analysis of Hepatic, Renal, and Metabolic Outcomes

Abstract

Microcystins (MCs) are cyanobacterial hepatotoxins that contaminate bloom-affected freshwater, drinking-water sources, aquatic food webs, and recreational environments. Human evidence for chronic or repeated exposure remains fragmented across study designs and organ systems. We systematically reviewed epidemiological evidence for hepatic, renal, and metabolic outcomes and integrated supporting mechanistic toxicology. PubMed, Scopus, and Web of Science searches identified 9021 records published from 1990 to 2025; an update search was conducted in April 2026. Risk of bias was assessed using a domain-based framework adapted from the Newcastle–Ottawa Scale and OHAT. The review was not prospectively registered. The qualitative evidence architecture retained 192 studies: 34 human epidemiological studies and 158 supporting mechanistic or contextual studies. Only seven independent adjusted estimates met the one-study–one-main-estimate rule for the primary quantitative synthesis. The hepatic meta-analysis included two estimates (OR 2.13; 95% CI, 1.29–3.53), the renal finding was a descriptive single-study estimate (OR 4.81; 95% CI, 1.96–11.81), and the metabolic meta-analysis included four estimates (OR 1.73; 95% CI, 1.00–2.98) with substantial heterogeneity (I2 = 91%; prediction interval, 0.56–5.36). Mechanistic evidence supported biological plausibility but was not treated as causal human evidence. Human evidence was relatively more consistent for hepatic outcomes, although it remained limited to two independent studies with different endpoints; renal and metabolic findings remain sparse or heterogeneous.