Development and validation of a hepatitis B-specific health-related quality-of-life instrument: CLDQ-HBV.

Hepatitis B virus (HBV) carries a large global burden. Efforts abound to decrease the burden, which necessitates reporting of patient-reported outcomes (PROs). We aimed to develop and validate an HBV-specific PRO instrument using the Chronic Liver Disease Questionnaire (CLDQ). Data were obtained from patients enrolled in our HBV registries who completed the CLDQ, Short Form-36 (SF-36) and FACIT-F. The sample was split randomly 1:1 into training and testing groups. A standard PRO instrument validation pipeline was used to develop and validate the new CLDQ-HBV instrument. HBV patients (n = 1,339) were 48 ± 13 years old, 60% male, 8% cirrhosis, with 53% receiving oral antivirals (OAV). After reduction of 10 redundant items, exploratory factor analysis for the remaining 19 items found 95% of variance was explained by five factors-emotional function, fatigue, systemic symptoms, worry and sleep. Good-to-excellent internal consistency was found: Cronbach's alphas 0.70-0.90 and item-to-own-domain correlations >0.50 for 18/19 items. Known-group validity tests discriminated between HBV patients with and without cirrhosis, with FIB-4 ≥ 3.25 vs <3.25, with and without history of depression or clinically overt fatigue (all p < 0.0001), and treatment (all p < 0.05, all but one <0.0001). After 48-week follow-up, HBV patients receiving OAV (N = 144) with ≥2.7 log 10/mL decline in HBV viral load experienced significant improvements in fatigue, worry and total CLDQ-HBV scores (p < 0.05). The newly developed CLDQ-HBV is a short, disease-specific PRO instrument for HBV patients which was developed and validated using large data set and an established methodology showing excellent psychometric characteristics.