Development and Validation of a Symptom-Based Patient-Reported Outcome Measure for MASH: The CLDQ-MASH Symptom...

Metabolic dysfunction-associated steatohepatitis (MASH) is associated with a substantial symptom burden. However, no validated symptom-focused patient-reported outcome instrument exists for this population. We aimed to develop and validate the MASH Symptom Questionnaire.

We analyzed subjects with metabolic dysfunction-associated steatotic liver disease (MASLD) from the global MASLD registry with clinical data and completed Chronic Liver Disease Questionnaire-MASH (CLDQ-MASH) instruments. For the new instrument development and preliminary validation, we used CLDQ-MASH items supplemented with symptom-related items from other generic instruments (development sample: n = 2,066) and expert input. A list of 50 symptom-related items was identified. After removal of redundancy, 36 items were retained and evaluated using exploratory factor analysis. Standard pipeline for validation of a patient-reported outcome instrument was applied. The instrument was validated using another independent validation sample from global MASLD registry (validation sample: n = 2,541).

In the development phase, 36 items were distributed in 8 symptom domains: mental, cognitive, fatigue, systemic, abdominal, health distress, sleep disturbance, and peripheral symptoms domains. Seven of 8 domains demonstrated a Cronbach alpha >0.80 (high internal consistency); the remaining peripheral symptoms domain included diverse items. The domain scores significantly discriminated across histologic disease severity (early fibrosis vs. F2-F3 vs. cirrhosis), liver stiffness categories (<10 vs. 10-20 vs. >20 kPa) in both development and independent validation samples. The instrument discriminated well based on nonhepatic comorbidities (type 2 diabetes, hypertension, psychiatric, sleep, pruritus, clinically overt fatigue, GERD, other GI disorders). Similar strong validation properties were noted in the independent validation sample.

The 36-item, 8-domain CLDQ-MASH Symptom Questionnaire represents the first validated, disease-specific symptom questionnaire for patients with MASH showing good psychometric properties. With further external validation, the CLDQ-MASH Symptom Questionnaire has the potential to serve as a standardized tool in both clinical research and routine practice to comprehensively assess disease burden and treatment response.