Background/Objectives: Interferon-free direct-acting antiviral (DAA) therapy cures chronic hepatitis C virus (HCV) infection, but its short-term effects on health-related quality of life (HRQoL) are captured differently by generic and disease-specific instruments. We examined longitudinal changes in utility scores and HRQoL in a multicenter Japanese cohort. Methods: Adults with chronic HCV completed the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L), the 8-Item Short-Form Health Survey (SF-8), and the Chronic Liver Disease Questionnaire (CLDQ) at baseline and at 12, 24, and 36 weeks after treatment initiation; 48-week data were included when available. Complete-case panels were analyzed for each instrument (SF-8, n = 112; CLDQ, n = 131; EQ-5D-5L, n = 128). Domain trajectories were summarized and compared with baseline. Results: By week 36, SF-8 general health improved significantly from 50.42 to 52.47, whereas vitality (50.73 to 52.55) and mental health (51.02 to 53.05) showed nonsignificant numerical increases. CLDQ showed improvements in worry (5.21 to 5.82) and total score (5.21 to 5.47). EQ-5D-5L utility values remained high and largely stable (0.913 to 0.920), suggesting ceiling effects in patients with relatively good baseline health status. External real-world evidence also suggested better on-treatment HRQoL with ribavirin-free regimens. Conclusions: In Japanese patients with HCV, interferon-free DAA therapy was associated with early improvements in symptom-proximal and mental domains of HRQoL. Generic utility scores changed little over the short term, indicating that disease-specific patient-reported outcome (PRO) instruments and utility measures should be used together for patient-centered assessment and cost–utility modeling.

Background/Objectives: Direct‑acting antivirals (DAAs) cure hepatitis C virus (HCV) infection and may improve health‑related quality of life (HRQoL), but responsiveness differs across instruments. We quantified longitudinal changes using EQ‑5D‑5L, SF‑8 and CLDQ in a multicenter Japanese cohort. Methods: Adults with chronic HCV completed patient‑reported outcomes (PROs) at baseline and 12/24/36 weeks (48 weeks where available). Complete‑case panels were defined per instrument (SF‑8 n=112, CLDQ n=131, EQ‑5D‑5L n=128). Domain trajectories were summarized and compared with baseline. Results: SF‑8 improved by 36 weeks: General Health 50.42→52.47, Vitality 50.73→52.55, Mental Health 51.02→53.05. CLDQ improved in Worry 5.21→5.82 and Total 5.21→5.47. EQ‑5D‑5L utilities remained high and stable (0.913→0.920), consistent with ceiling effects at high baseline health. External real‑world data indicated better on‑treatment HRQoL with ribavirin‑free regimens. Conclusions: Interferon‑free DAAs yield early, clinically meaningful HRQoL gains in symptom‑proximal and mental domains, while generic utilities show minimal short‑term change. Combining disease‑specific PROs with utilities is essential for patient‑centered care and for parameterizing cost‑utility models in Japan.