INTRODUCTION: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized in patients with primary biliary cholangitis (PBC). While metabolic comorbidities are expected to worsen outcomes, the clinical impact of MASLD in PBC remains uncertain. We investigated whether concomitant MASLD modifies hepatic and cardiovascular outcomes in patients with PBC. METHODS: We conducted a retrospective international cohort study using de-identified electronic health records from the TriNetX global research network, including 172 healthcare organizations between 2010 and 2025. Adult patients with PBC with and without MASLD were matched using propensity score matching (1:1) to balance baseline characteristics. The primary outcomes were all-cause mortality. Major adverse cardiovascular events (MACE) and hepatic decompensation were evaluated as secondary outcomes. Additional outcomes included hepatocellular carcinoma, liver transplantation, and one-year biochemical response (ALP normalization). RESULTS: Among 30 934 patients with PBC (78.9% female; mean age 68 years), 5955 (19.2%) had concomitant MASLD. After matching, 10 856 patients (5428 per group) were included. Over a mean follow-up of 4 years, patients with PBC-MASLD had a lower risk of all-cause mortality (HR 0.60; 95% CI 0.54-0.67) and hepatic decompensation (HR 0.82; 95% CI 0.71-0.93), but higher risk of MACE (hazard ratio HR 1.30; 95% CI 1.14-1.48). One-year biochemical response rates were comparable between groups. Findings remained consistent across multiple sensitivity analyses. CONCLUSION: MASLD identifies a distinct metabolic phenotype of PBC characterized by increased cardiovascular risk but paradoxically lower mortality and hepatic decompensation. These findings highlight the need to integrate cardiovascular risk assessment into the management of patients with PBC.
Tan et al. (Mon,) studied this question.