Epidemiological and Clinical Characteristics of Human Hepegivirus 1 Infection in Patients with Hepatitis C

Transmission of human hepegivirus 1 (HHpgV-1), a novel human pegivirus, is closely associated with hepatitis C virus (HCV). The impact of HHpgV-1 viremia on HCV infection is unknown. This study aimed to (a) evaluate the impact of HHpgV-1 viremia on HCV viral load and liver injury and (b) elucidate the clinical and molecular epidemiology of HHpgV-1 infection. Methods: Individuals with HHpgV-1 viremia (cases) were identified by screening plasma from 655 HCV-infected adults. HHpgV-1 isolates were sequenced for phylogenetic analysis, and viral load was quantified. Cases were age- and sex-matched to HCV-infected individuals without HHpgV-1 viremia (controls) in a 1:3 ratio. A retrospective case-control analysis was performed to identify differences in HCV viral load and parameters of liver injury. Results: Among HCV-infected adults, 16/655 (2.4%) had HHpgV-1 viremia. Risk groups for HHpgV-1 infection included intravenous drug users, blood product recipients, tattoo recipients, and men who have sex with men. Viral sequences clustered into 2 distinct HHpgV-1 genogroups. Cases had a higher mean HCV viral load than controls, with difference between means of 0.58 log₁₀ IU/mL (P =. 009). Cases were more likely to have an HCV viral load >5 log₁₀ IU/mL (P =. 028). Multiple regression demonstrated the impact of HHpgV-1 viral load and infection status on HCV viral load. HHpgV-1 infection was not associated with higher liver function tests, fibrosis scores, or imaging abnormalities. Conclusions: HHpgV-1 viremia is associated with a higher HCV viral load in co-infected patients. HHpgV-1 infection does not affect progression of HCV-related liver disease.