Real-world efficacy and safety of sofosbuvir/velpatasvir/voxilaprevir in treatment-naive and treatment-experienced chronic hepatitis c patients: a single-center study.

BACKGROUND: Although international guidelines primarily position the sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) combination as a salvage therapy for treatment-experienced patients, specific national reimbursement policies in Türkiye have uniquely positioned this regimen as a first-line treatment for treatment-naive individuals. Because international protocols largely restrict this combination to salvage settings, there remains limited real-world evidence regarding its efficacy and safety as a first-line therapy. This study aims to evaluate the real-world clinical performance of the SOF/VEL/VOX regimen in both treatment-naive and treatment-experienced patients with chronic hepatitis C (CHC), thereby providing additional real-world evidence for this underexplored clinical setting.

METHODS: This retrospective, single-center observational longitudinal cohort study included 124 non-cirrhotic patients with CHC treated with the SOF/VEL/VOX regimen. The cohort comprised 86 (69.3%) treatment-naive and 38 (30.6%) treatment-experienced patients. Treatment-naive patients received the regimen for 8 weeks, whereas treatment-experienced patients received it for 12 weeks. The primary endpoint was sustained virologic response at 12 weeks post-treatment (SVR12). Liver fibrosis was evaluated using the aspartate aminotransferase-to-platelet ratio index (APRI).

RESULTS: The mean age was 42 years, with a male predominance (81.4%) and a substantial proportion of individuals from the incarcerated population (44.3%). The most prevalent clinical comorbidities within the cohort were hypertension (8.1%) and diabetes mellitus (8.1%). Genotype 1 (58.1%) and genotype 3 (40.3%) were the most common variants. Regarding baseline differences, treatment-experienced patients were younger (mean age: 37.4 vs. 44.1 years) and exhibited a higher prevalence of genotype 1a infection compared to the treatment-naive group. At SVR12, hepatitis C virus ribonucleic acid (HCV RNA) clearance was achieved in 100% of both treatment-naive and treatment-experienced patients, with no significant difference between the groups (p = 1.000). Concomitant with virological clearance, levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) significantly decreased (p < 0.001), reflecting the resolution of hepatic necroinflammation. Furthermore, the median APRI score decreased from 0.28 at baseline to 0.14 at SVR12 (p < 0.001), reflecting the rapid resolution of hepatic necroinflammation following viral clearance rather than definitive structural fibrosis regression in this predominantly non-cirrhotic cohort. The regimen was well tolerated, with no serious adverse events or treatment discontinuations. Minor transient adverse events (3.2%) resolved completely during follow-up.

CONCLUSION: This real-world study demonstrate that the SOF/VEL/VOX combination achieved a 100% SVR12 rate with excellent tolerability in both treatment-naive and treatment-experienced CHC patients. These findings support the use of SOF/VEL/VOX as a first-line option for treatment-naive patients, particularly in settings where alternative pangenotypic regimens are unavailable, while providing high virological efficacy and promoting rapid resolution of hepatic necroinflammation.