The Genotypes/Subtypes and Antiviral Drug Resistance of the Hepatitis C Virus from Patients in a Tertiary Care Hospital in Nepal.

While direct-acting antivirals (DAAs) are available for the treatment of chronic Hepatitis C virus (HCV) patients in Nepal, knowledge of the circulating genotypes/subtypes and drug target gene mutations of HCV is currently unavailable. Here, we describe HCV genotypes/subtypes and identify antiviral target gene mutations in patients at a tertiary care hospital using genome data. A cross-sectional study was conducted from December 2019 to February 2024, where PCR followed by whole genome sequencing was performed to identify HCV genotypes/subtypes and drug target gene mutations. Among all the patients who tested positive for anti-HCV, 70.6% (149/211) were HCV RNA positive, while 68.2% (30/44) were genotype/subtype 3a, followed by 1a (18.2%, 8/44) and others (13.6%, 6/44), including new subtypes 3g and 3i from Nepal. Subtype 3a was also the dominant subtype (≥70%) among intravenous drug users and sexual routes of transmission. We found 70.5% of the samples with resistant mutations in the NS3/4A region, 22.7% in NS5A, and 45.5% in NS5B. Resistant mutations against sofosbuvir, pibrentasvir, velpatasvir, daclatasvir, and dasabuvir were found at 25%, 18%, 16%, 16%, and 2%, respectively, mostly on subtype 3a. The predominant HCV genotype/subtype in our patient group was 3a, and resistance mutations against direct-acting antivirals were found in most untreated patients.