Liver international : official journal of the International Association for the Study of the Liver · 2026
Environmental Endocrine-Disrupting Chemicals and Metabolic Dysfunction-Associated Steatotic Liver Disease.
СтатьяМетаанализСистематический обзорНазвание и аннотация: Перевод в очереди
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Zhao Yiwei, He Huifen, Zeng Jiao, Zhang Jingjing
Аннотация
BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly termed non-alcoholic fatty liver disease (NAFLD), represents the most prevalent chronic liver condition worldwide, affecting approximately 25%-30% of the global adult population. Endocrine-disrupting chemicals (EDCs)-including phthalates, bisphenols, per- and polyfluoroalkyl substances (PFAS), persistent organic pollutants (POPs) and heavy metals-are ubiquitous environmental contaminants with established metabolic toxicity. However, the quantitative association between EDC exposure and MASLD prevalence remains incompletely characterised. We conducted a systematic review and meta-analysis to synthesise the current epidemiological evidence on this association.
METHODS: We systematically searched PubMed, Embase, Web of Science and the Cochrane Library from inception through January 2026, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines (PROSPERO: CRD420261298624). Studies were eligible if they reported quantitative associations between measured EDC exposures and MASLD/NAFLD/metabolic-associated fatty liver disease (MAFLD) outcomes in human populations. Two investigators independently screened records, extracted data and assessed methodological quality using a customised Newcastle-Ottawa Scale (NOS). Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. Heterogeneity was assessed via the I2 statistic. Funnel plot asymmetry and Egger's test were used to evaluate publication bias. Sensitivity analyses were performed using leave-one-out methods.
RESULTS: Of 427 records identified, 42 studies encompassing diverse global populations met inclusion criteria and were incorporated into the quantitative synthesis. The meta-analysis demonstrated that: Phthalates: mono (2-ethyl-5-carboxypentyl) phthalate (MECPP; weighted mean difference [WMD]: 2.40, 95% CI: 0.71-4.09), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP; WMD: 2.46, 95% CI: 0.81-4.10) and monobenzyl phthalate (MBzP; WMD: 1.84, 95% CI: 0.10-3.59) showed significant positive associations with MASLD prevalence; pooled analysis of phthalate mixtures yielded an overall OR of 1.17 (95% CI: 1.13-1.21; I2 = 41.4%). Bisphenols: pooled analysis demonstrated a significant positive association with MASLD (OR: 1.29, 95% CI: 1.09-1.50; I2 = 73.0%), with bisphenol A (BPA; OR: 1.32, 95% CI: 0.92-1.72), bisphenol S (BPS; OR: 1.47, 95% CI: 0.96-1.98) and bisphenol F (BPF; OR: 1.19, 95% CI: 0.77-1.61) contributing to this effect. PFAS: the overall pooled effect was OR 0.95 (95% CI: 0.91-1.00; I2 = 22.9%). POPs: the overall OR was 1.30 (95% CI: 1.22-1.37; I2 = 29.2%), with organochlorine pesticides (OCPs; OR: 1.30, 95% CI: 1.19-1.42) and polychlorinated biphenyl (PCB)/OCP combinations demonstrating significant associations. Heavy metals/metalloids: mercury (Hg) demonstrated the strongest positive association (OR: 1.60, 95% CI: 1.15-2.04; I2 = 87.3%), followed by lead (Pb; OR: 1.40, 95% CI: 1.02-1.78) and cadmium (Cd; OR: 1.30, 95% CI: 1.09-1.51; I2 = 79.2%); the overall metals pooled OR was 1.26 (95% CI: 1.16-1.37; I2 = 79.9%). Methodological quality assessed by NOS ranged from 6 to 9 points, with the majority of studies scoring ≥ 7.
CONCLUSIONS: This meta-analysis of observational studies suggests that environmental exposure to several major EDC classes-including phthalates, bisphenols, persistent organic pollutants and certain heavy metals-is associated with a higher prevalence of MASLD, although the magnitude and consistency of associations vary substantially across chemical classes and individual compounds. Findings for PFAS were heterogeneous and compound-specific. Given the predominantly cross-sectional nature of the available evidence and the considerable between-study heterogeneity, causal inference cannot be drawn. These findings should be interpreted as hypothesis-generating and underscore the need for prospective multi-pollutant studies and mechanistic investigations to clarify the role of EDCs in MASLD pathogenesis.
METHODS: We systematically searched PubMed, Embase, Web of Science and the Cochrane Library from inception through January 2026, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines (PROSPERO: CRD420261298624). Studies were eligible if they reported quantitative associations between measured EDC exposures and MASLD/NAFLD/metabolic-associated fatty liver disease (MAFLD) outcomes in human populations. Two investigators independently screened records, extracted data and assessed methodological quality using a customised Newcastle-Ottawa Scale (NOS). Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. Heterogeneity was assessed via the I2 statistic. Funnel plot asymmetry and Egger's test were used to evaluate publication bias. Sensitivity analyses were performed using leave-one-out methods.
RESULTS: Of 427 records identified, 42 studies encompassing diverse global populations met inclusion criteria and were incorporated into the quantitative synthesis. The meta-analysis demonstrated that: Phthalates: mono (2-ethyl-5-carboxypentyl) phthalate (MECPP; weighted mean difference [WMD]: 2.40, 95% CI: 0.71-4.09), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP; WMD: 2.46, 95% CI: 0.81-4.10) and monobenzyl phthalate (MBzP; WMD: 1.84, 95% CI: 0.10-3.59) showed significant positive associations with MASLD prevalence; pooled analysis of phthalate mixtures yielded an overall OR of 1.17 (95% CI: 1.13-1.21; I2 = 41.4%). Bisphenols: pooled analysis demonstrated a significant positive association with MASLD (OR: 1.29, 95% CI: 1.09-1.50; I2 = 73.0%), with bisphenol A (BPA; OR: 1.32, 95% CI: 0.92-1.72), bisphenol S (BPS; OR: 1.47, 95% CI: 0.96-1.98) and bisphenol F (BPF; OR: 1.19, 95% CI: 0.77-1.61) contributing to this effect. PFAS: the overall pooled effect was OR 0.95 (95% CI: 0.91-1.00; I2 = 22.9%). POPs: the overall OR was 1.30 (95% CI: 1.22-1.37; I2 = 29.2%), with organochlorine pesticides (OCPs; OR: 1.30, 95% CI: 1.19-1.42) and polychlorinated biphenyl (PCB)/OCP combinations demonstrating significant associations. Heavy metals/metalloids: mercury (Hg) demonstrated the strongest positive association (OR: 1.60, 95% CI: 1.15-2.04; I2 = 87.3%), followed by lead (Pb; OR: 1.40, 95% CI: 1.02-1.78) and cadmium (Cd; OR: 1.30, 95% CI: 1.09-1.51; I2 = 79.2%); the overall metals pooled OR was 1.26 (95% CI: 1.16-1.37; I2 = 79.9%). Methodological quality assessed by NOS ranged from 6 to 9 points, with the majority of studies scoring ≥ 7.
CONCLUSIONS: This meta-analysis of observational studies suggests that environmental exposure to several major EDC classes-including phthalates, bisphenols, persistent organic pollutants and certain heavy metals-is associated with a higher prevalence of MASLD, although the magnitude and consistency of associations vary substantially across chemical classes and individual compounds. Findings for PFAS were heterogeneous and compound-specific. Given the predominantly cross-sectional nature of the available evidence and the considerable between-study heterogeneity, causal inference cannot be drawn. These findings should be interpreted as hypothesis-generating and underscore the need for prospective multi-pollutant studies and mechanistic investigations to clarify the role of EDCs in MASLD pathogenesis.