The association of primary biliary cholangitis with metabolic syndrome and metabolic dysfunction-associated steatotic liver disease

The precise risk factors contributing to the onset of primary biliary cholangitis (PBC) are still unclear. Although numerous findings indicate that genetic and environmental factors may contribute to PBC by disrupting immune tolerance, recent data also indicate a potential concomitance between PBC and metabolic syndrome, as well as metabolic dysfunction-associated steatotic liver disease (MASLD). In this review, we present a comprehensive examination of the available evidence on the prevalence, pathogenesis, and impact of the coexistence of PBC with MASLD and/or metabolic syndrome. Histologic observations have reported simultaneous occurrences of MASLD and PBC, and the detection of anti-mitochondrial antibodies in MASLD raises concerns about a potential underlying pathophysiologic connection. Conflicting data exist regarding the effect of coexistence of PBC and MASLD: smaller histology-based studies suggest worsened biliary damage and long-term outcomes, whereas the largest available cohorts find no independent adverse effect. Emerging evidence indicates that the cumulative burden of metabolic syndrome, rather than hepatic steatosis alone, may be the primary driver of fibrosis progression in PBC. Evidence suggests a correlation of PBC and metabolic syndrome-related conditions, such as obesity, hyperlipidemia, insulin resistance, and hypertension. This review synthesizes current knowledge on the complex interplay among these conditions and identifies key knowledge gaps that warrant further investigation, with the goal of informing screening strategies and clinical management in patients with overlapping diagnoses.