IN PATIENTS with primary sclerosing cholangitis (PSC), metabolic dysfunction–associated steatotic liver disease (MASLD) overlap was associated with significantly greater pruritus intensity but paradoxically lower fatigue severity, according to a US single-centre analysis of patient-reported outcomes. MASLD overlap prevalence was one in three within this cohort, suggesting that metabolic liver changes may modulate symptom profiles in PSC.
MASLD Overlap Alters Clinical Features and Symptoms
The study included 103 patients with PSC from a tertiary autoimmune liver disease registry between 2018 and 2024. MASLD overlap was defined based on imaging or biopsy evidence of hepatic steatosis alongside at least one cardiometabolic risk factor. Patients with MASLD overlap were older and had higher body mass index than those with PSC alone. Small bile duct involvement was more common in the overlap group.
Patient-reported outcomes for fatigue and pruritus were captured with validated instruments, with ordinal logistic regression models adjusting for clinically relevant factors. MASLD overlap emerged as a significant determinant of pruritus severity: those with the overlap had more than threefold higher odds of greater pruritus intensity than patients without MASLD overlap. In contrast, MASLD overlap was linked to reduced fatigue severity, with approximately two-thirds lower odds of high fatigue intensity after adjustment.
Clinical Implications for Hepatology Practice
These findings indicate that the coexistence of metabolic steatosis may influence symptom burden in PSC beyond traditional cholestatic mechanisms. The unexpectedly lower fatigue levels in MASLD overlap patients challenge assumptions about symptom patterns in overlapping liver disease states and suggest under-recognised biological influences, possibly metabolic or inflammatory pathways.
Given the high prevalence of MASLD in general populations with metabolic risk, clinicians should consider routine assessment of steatosis and symptom burdens such as pruritus and fatigue in PSC. Future research should define mechanistic underpinnings and assess whether these symptom differences translate into distinct management needs.
Reference
Rojas-Amaris N et al. Impact of Metabolic Dysfunction-Associated Steatotic Liver Disease on Fatigue and Pruritus in Primary Sclerosing Cholangitis: A U.S. Single-Center Study. J Clin Med. 2025;14(22):8083.
