Impact of Metabolic Dysfunction-Associated Steatotic Liver Disease on Fatigue and Pruritus in Primary Sclerosing Cholangitis: A U.S. Single-Center Study

<b>Background and Aims:</b> Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of liver disease in the United States and frequently coexists with other liver diseases. Despite growing interest, the presence of MASLD in patients with primary sclerosing cholangitis (PSC) remains underexplored. This study aimed to assess the prevalence and characteristics of the MASLD-PSC overlap syndrome, with a specific focus on patient-reported outcomes such as pruritus and fatigue. <b>Methods:</b> A cross-sectional analysis was performed within a prospective cohort of patients with PSC enrolled in the Autoimmune Liver Diseases Registry at a United States tertiary medical center (2018-2024). MASLD overlap was established based on evidence of hepatic steatosis on liver imaging or biopsy, combined with at least one cardiometabolic risk factor. Fatigue and pruritus were assessed using the Chronic Liver Disease Questionnaire (CLDQ) and the 5D Itch Scale. Ordinal logistic regression models were used to explore the potential impact of MASLD overlap on fatigue and pruritus severity. <b>Results:</b> Among 103 PSC patients, 33% had MASLD overlap. These patients were older (55 vs. 46 years, <i>p</i> = 0.006), had a higher BMI (30 vs. 25 kg/m², <i>p</i> < 0.001), and were more likely to have small bile duct involvement (43% vs. 12%, <i>p</i> = 0.002). A history of liver transplantation (LT) was noted in 18% of PSC-only patients, compared to 3% of those with PSC/MASLD (<i>p</i> = 0.055). MASLD overlap was significantly associated with higher pruritus intensity (OR 3.09, 95% CI 1.02-9.28, <i>p</i> = 0.044), but was paradoxically linked to lower fatigue levels (OR 0.37, 95% CI 0.16-0.85, <i>p</i> = 0.020). <b>Conclusions:</b> Patients with PSC/MASLD exhibit distinct clinical features. MASLD overlap was found to significantly impact patient-reported outcomes, with lower fatigue intensity but increased pruritus severity, suggesting a role for metabolic or inflammatory pathways, warranting further investigation.