Analysis of Genetic Characteristics of Hepatitis C Virus among Sentinel Surveillance Populations in Fujian Province, China from 2022 to 2025

Objective To analyze the genotype distribution, evolution, and characteristics of resistance-associated substitutions (RASs) of Hepatitis C Virus (HCV) among sentinel surveillance populations in Fujian Province from 2022 to 2025, and to provide a scientific basis for HCV prevention and control. Methods The hepatitis C incidence report data from 2022 to 2025 in Fujian Province were obtained from the China CDC Information System. Full-length HCV genome sequences were obtained through high-throughput sequencing, and bioinformatics software was employed to analyze genetic characteristics and RAS distribution. Results From 2022 to 2025, sentinel surveillance in Fujian Province revealed that HCV infections were predominantly subtype 1b, with escalating trends observed in subtypes 3b and 6a. Phylogenetic analysis demonstrated that most 1b, 3b, and 6a sequences clustered closely with Guangdong Province sequences, while some lineages also grouped with international sequences from Japan and Denmark. Sequences of subtypes 1a and 2a were more likely to cluster with international sequences. In the HCV NS3/4A region, resistance-associated substitutions (RASs) S122G/N/C occurred most frequently in subtypes 1b and 6a (31/91). In the NS5A region, RASs conferring higher drug resistance included L31V and Y93H, R30Q and L28M in subtype 1b, and Q30K+L31M in subtype 3b. In the NS5B region, RASs-C316N was predominantly detected in subtype 1b (21/32), and when coexisting with S556G, it conferred higher resistance to DSV. Concurrent presence of RASs in both NS5B and NS5A regions reduced SOF treatment efficacy. Conclusions The genetic distribution of sentinel populations in Fujian Province tends to be increasingly complex. Population mobility and overseas importation are important factors in virus transmission. Drug resistance-related substitution mutations are commonly present in sentinel populations, and using whole-genome sequencing to track drug resistance mutations generated by genetic diversity in epidemic strains is very important for accurately guiding treatment of hepatitis C patients.