In this study, we characterized the molecular epidemiology of 61 HCV-infections in Huazhou County, which ranked among the top five counties in Shaanxi Province, Northwest China, for HCV infection prevalence. All 61 strains belonged to HCV subtype 2a in distinct phylogenetic clusters indicating that HCV has been introduced independently followed by local transmissions with estimated dates of 8 to 20 years before sampling by NS5B sequence analyses. Among 61 HCV-infections, 26.2% were members of the Huazhou HCV transmission network. Having a history of blood transfusion and living in Shi village were more likely to be in the membership of transmission network. This is, as far as we are aware, the first phylogenetic analysis of the HCV transmission network among the general population in Shaanxi province. It provides helpful knowledge to better understand HCV transmission risk in high-prevalence regions and offers suggestions for public-prevention strategy.
At present, the distributions of HCV genotypes in Mainland China show remarkable geographic and demographic differences. Subtype 2a, once predominantly transmitted through contaminated blood transfusions prior to the 1900s, has seen a decline in prevalence after the 1992 ban on paid blood donations, but it remains to be one of the most prevalent subtypes alongside subtype 1b. Conversely, subtypes 3a, 3b, and 6a, associated with injection drug use, have increased, according to recent studies [12]. Shaanxi province had less diversified genotype distribution patterns compared to southern Chinese provinces, with subtype 2a being particularly prevalent [5, 12–13]. Our study revealed that subtype 2a was independently multiple introduced in Huazhou County between 8 to 20 years ago, with most strains that originated from northwest China. These strains contributed to the local epidemic over the last twenty years.
Subtype 2a was found in individuals with intravenous drug use, unsafe medical practices, and high risk sexual behaviors [11]. Reports have highlighted unsafe medical procedures as the primary risk factors for HCV outbreaks across various Chinese provinces from 2011 to 2012 [14–15]. Despite the government has significantly reinforced nosocomial infection control through the China Viral Hepatitis Prevention and Control Program over the last decade, the potential for unsafe medical practices in private clinics to contribute to the spread of HCV in Huazhou County cannot be fully excluded. It is suggested that relevant government agencies should enhance the regulatory oversight of healthcare facilities, in rural areas, to curb the transmission of HCV.
In our study, only 26.2% of participants from Huazhou County were identified in subtype 2a phylogenetic clusters, a rate lower than those reported in similar studies among HIV/HCV coinfected patients in Guangdong (44.0%) [7] and Dehong (39.1%) [9], China, as well as among drug users in Vancouver, Canada (31.0%) [16]. The variations in the study populations might have accounted for the different results. Our study found an association between clustering in the transmission network and the history of blood transfusions, which previously recognized as a risk factor for acquiring hepatitis C [17–18]. Although it is currently unlikely for individuals to infect hepatitis C through transfusions, our phylogenetic analysis indicated that individuals with a history of blood transfusions are at a heightened risk of transmitting HCV, underscoring the necessity for targeted interventions for this demographic. Furthermore, the residence region was another factor associated with network clustering. Specifically, individuals from Shi Village exhibited a high degree of clustering within the transmission network, indicating a closely-knit genetic relationship and suggesting a potential social structure of closely related transmissions centered around Shi Village. This finding emphasized the urgent need for enhanced treatment and prevention in this community. Interventions that focus on traits linked to the potential risks of molecular transmission has proven effective in preventing further infections in settings where injecting or sexual network data is unavailable [19]. Consequently, providing treatment as a preventive service to residents of Shi Village and individuals who have a history of blood transfusions could be an efficient way to prevent the spread of HCV.
This study has several limitations. First, the small sample size of the study limits the findings. The samples were collected for a case-control study on the risk factors for hepatitis C infection. About half of the patients were unable to obtain the genetic data. Individuals who were diagnosed with HCV within the last three years may have recovered. Furthermore, compared to the patient group, the control group had more HCV RNA positive samples in the study. People who have chronic hepatitis C may not be aware that they have the infection because it is usually asymptomatic. It is recommended that the county-wide coverage of HCV testing and molecular epidemiology research be expanded. Second, no phylogenetic relationships within Shaanxi Province have been found. This could be due to the fact that, in the past 10 years, relatively little sequence data of HCV subtype 2a from Shaanxi Province has been published.