Outcomes and predictors of treatment failure following direct-acting antiviral therapy in chronic hepatitis C: A retrospective cohort study

Objective: To evaluate the effectiveness of direct-acting antivirals (DAAs) in patients with chronic hepatitis C, assess changes in liver function and hepatic fibrosis following treatment, and identify independent predictors of treatment failure. Methods: This retrospective cohort study included patients who received DAA therapy at Hospital Kuala Lumpur between January 2020 and December 2023. Sustained virologic response (SVR) was assessed at least 12 weeks post-treatment by reverse transcription-polymerase chain reaction for hepatitis C virus (HCV) RNA. Demographic, clinical, and laboratory data were collected and analyzed. Multiple logistic regression analysis was performed to identify independent predictors of treatment failure. Results: A total of 335 patients in the study. The overall SVR rate was 89%. After achieving SVR, significant improvements were observed in liver enzyme levels and non-invasive liver fibrosis scores, whereas the overall Model for End-Stage Liver Disease (MELD) scores remained unchanged. Significant independent predictors of treatment failure included non-compliance with DAA therapy adjusted odds ratio (aOR) 68.3; 95% confidence interval (95% CI ) 16.3-285.0; P <0.001, treatment with sofosbuvir/velpatasvir (aOR 6.1; 95% CI 1.4-26.5; P =0.015), MELD score of 10-15 (a OR 4.6; 95% CI 1.1-18.2; P =0.031), HCV genotype 3 infection (a OR 4.5; 95% CI 1.1-17.6; P =0.031), and elevated serum total bilirubin level (a OR 1.1; 95% CI 1.0-1.1; P =0.003). Conclusions: DAA therapy yielded a high SVR rate, and treatment failure was strongly associated with non-adherence to therapy and advanced liver disease. These findings underscore the necessity of adherence support, early diagnosis, and individualized clinical management to optimize treatment outcomes in patients with chronic hepatitis C.