Determinants of Nonresponse to Direct-Acting Antivirals in Chronic Hepatitis C Infection: A Narrative Review

Abstract

Direct-acting antivirals (DAAs) have transformed the treatment landscape for chronic hepatitis C virus (HCV) infection, offering sustained virology response rates exceeding 95% across diverse patient populations. However, patients fail to respond to therapy, resulting in persistent infection and continued risk of liver-related morbidity and mortality. A comprehensive review of published literature was conducted to identify host, viral, and disease-related factors associated with treatment failure in the DAA era. Particular focus was given to studies examining cirrhosis, comorbid conditions, virological factors, prior treatment history, and socio-behavioral determinants. The most consistently reported predictors of nonresponse include advanced liver disease (especially decompensated cirrhosis), thrombocytopenia, hypoalbuminemia, high fibrosis scores, HCV genotype 3, prior treatment failure, HIV or HBV co-infection, diabetes mellitus, and poor adherence. Patients with multiple risk factors often require individualized treatment strategies and closer clinical monitoring. Thus, this review aims to explore and summarize the key predictors of nonresponse to DAA therapy in patients with chronic hepatitis C, based on current clinical and epidemiological evidence.