Serum polychlorinated biphenyls and risk of metabolic dysfunction-associated steatotic liver disease: Cross-sectional and prospective analyses from the Dongfeng-Tongji cohort.

Polychlorinated biphenyls (PCBs) are persistent endocrine-disrupting pollutants, yet evidence linking PCB exposure to metabolic dysfunction-associated steatotic liver disease (MASLD) remains limited, particularly across disease onset and fibrosis burden. We measured serum concentrations of seven PCB congeners (PCB-28, PCB-52, PCB-101, PCB-118, PCB-138, PCB-153, and PCB-180) in 2013 among 3260 participants from the Dongfeng-Tongji cohort, a prospective study of retired employees in China, with follow-up examinations every five years. We examined associations of individual congeners and congener-group summary measures with prevalent and 5-year incident MASLD using multivariable logistic regression. Restricted cubic splines and mixture models characterized dose-response and mixture effects, with subgroup analyses by gender and lifestyle factors. We further assessed liver injury and fibrosis indicators using multivariable logistic and linear regression, including multinomial logistic models for Fibrosis-4-based risk categories. Overall, higher levels of PCB-28, PCB-118, PCB-153, lower- and higher-chlorinated PCBs, and ΣPCBs were associated with increased MASLD prevalence, with stronger associations among males, ever smokers, and frequent meat consumers. Mixture models assigned the greatest weights to PCB-28 and PCB-118. Prospectively, higher ΣPCBs predicted incident MASLD, mainly driven by PCB-118 (OR = 1.70, 95% CI: 1.10-2.64). PCBs were also associated with increased odds of liver injury and higher ALT, GGT, and ALP. Among participants with MASLD, higher PCBs were associated with higher dAAR and FIB-4, and greater odds of high fibrosis risk. These findings indicate that higher PCB exposure was linked to increased MASLD risk, liver injury, and fibrosis burden, suggesting PCBs are modifiable environmental risk factors for MASLD.