Abstract
BACKGROUND: Hepatitis C virus (HCV) infection is associated with neuropsychiatric symptoms, including depression and psychosomatic complaints. While direct-acting antivirals (DAAs) have revolutionized HCV treatment, their impact on mental health and systemic symptoms remains unclear. This study aimed to compare depression severity, liver fibrosis scores, and psychosomatic symptoms in treatment-naive (Tx-naive) and treatment-experienced (Tx-experienced) patients who achieved sustained virologic response (SVR). MATERIALS AND METHODS: A cross-sectional observational study was conducted at two tertiary care hospitals in Pakistan. Patients with chronic HCV were categorized into Tx-naive and Tx-experienced SVR-achieved groups. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9), while fibrosis severity was determined using Fibrosis-4 (FIB-4) scores. Psychosomatic symptoms, including myalgia, asthenia, and functional dyspepsia, were documented. Statistical comparisons were performed using independent t-tests, Mann-Whitney U tests, and Chi-squared tests. RESULTS: A total of 142 patients were analyzed, with 69 in the Tx-naive group and 73 in the Tx-experienced SVR-achieved group. PHQ-9 scores did not significantly differ between groups (p=0.343) or FIB-4 scores (p=0.691). The prevalence of psychosomatic symptoms was comparable across both cohorts, with no statistically significant differences in individual symptoms such as asthenia, myalgia, or burning feet syndrome (all p>0.05). CONCLUSIONS: The findings suggest that HCV itself, rather than DAA therapy, is the primary contributor to depression and somatic symptoms. Achieving SVR does not significantly alter mental health or systemic symptom burden. These results highlight the need for long-term neuropsychiatric monitoring in HCV survivors, as symptoms may persist despite viral clearance. Future research should explore the biological underpinnings of these persistent complaints and assess potential interventions for improving patient quality of life.