Factors Associated With Hepatitis C Treatment Failure: A Regional Case–control Study in Kazakhstan

Introduction: Direct-acting antiviral therapy achieves high cure rates in chronic hepatitis C; however, a minority of patients do not achieve a sustained virologic response. The aim of this study was to evaluate clinical, demographic, and virologic factors associated with failure to achieve a sustained virologic response among patients with chronic hepatitis C treated in the Turkestan Region of Kazakhstan. Methods: We performed a retrospective case-control study of 168 adults treated with direct-acting antivirals between January 2018 and December 2022. The control group comprised 126 patients who achieved a sustained virologic response, and the case group comprised 42 patients without a sustained virologic response. Demographic characteristics, disease duration, treatment duration, adherence, hepatitis C virus genotype, pretreatment alanine aminotransferase level, liver elastography, and fibrosis stage were analyzed. Results: Patients without a sustained virologic response had higher pretreatment alanine aminotransferase levels (p=0.03), higher liver stiffness values on elastography (p=0.007), and a longer duration of chronic hepatitis C before treatment (p<0.0001). Genotype 3 was more frequent among cases than controls (59.5% vs 24.6%; p<0.0001), and F4 fibrosis was also more common (40.5% vs 10.3%; p<0.0001). Treatment duration greater than 12 weeks (p=0.02) and lower treatment adherence (p<0.0001) were more frequent in the case group. Age, sex, ethnicity, and previous pegylated interferon/ribavirin therapy did not differ significantly between groups. Conclusion: Failure to achieve a sustained virologic response was associated with greater biochemical activity, more advanced liver fibrosis, longer disease duration, genotype 3 infection, and lower treatment adherence. Adherence represents a potentially modifiable factor that may be addressed through structured follow-up and patient counseling.