The Natural History of Hepatitis C Virus Infection: Host, Viral, and Environmental Factors

Author/Creator ORCID





Citation of Original Publication

Thomas DL, Astemborski J, Rai RM, et al. The Natural History of Hepatitis C Virus Infection: Host, Viral, and Environmental Factors. JAMA. 2000;284(4):450–456. doi:10.1001/jama.284.4.450


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Context Hepatitis C virus (HCV) infection may resolve (viral clearance), persist without complications, or cause end-stage liver disease (ESLD). The frequency and determinants of these outcomes are poorly understood. Objective To assess the incidence and determinants of viral clearance and ESLD among persons who acquired HCV infection from injection drug use. Design and Setting Community-based prospective cohort study with enrollment in 1988-1989 and a median follow-up of 8.8 years. Subjects A total of 1667 persons aged 17 years or older with a history of injection drug use and an HCV antibody–positive test result during follow-up. Main Outcome Measures Viral clearance was assessed in a subset of 919 patients and defined as failure to detect HCV RNA in at least 2 consecutive samples collected 5 or more months apart. End-stage liver disease was assessed at semiannual visits and by review of medical records and death certificates and defined by the presence of ascites, esophageal varices, or hepatic encephalopathy, or when ESLD was stated as a cause of death. Results Viral clearance was observed in 90 persons who were compared with 722 with persistent viremia, while the viremia of 107 was not resolved. Viral clearance occurred more often in nonblacks (adjusted odds ratio [OR], 5.15; 95% confidence interval [CI], 2.60-10.17) and those not infected with human immunodeficiency virus (HIV) (adjusted OR, 2.19; 95% CI, 1.26-3.47). Forty cases of ESLD were observed throughout follow-up (incidence, 3.1 per 1000 person-years). In a multivariate model, risk of ESLD was higher for persons aged 38 years or older at enrollment (adjusted relative incidence, 3.67; 95% CI, 1.96-6.88) and who reported ingestion of more than 260 g of alcohol per week (adjusted relative incidence, 3.60; 95% CI, 1.73-7.52). Of 210 patients without ESLD randomly selected for biopsy, only 2 had cirrhosis. Conclusions Our results indicate that although HCV infection can be self-limited or associated with ESLD, the majority of adults have persistent viremia without clinically demonstrable liver disease. Further research is needed to explain the less frequent clearance of HCV infection among black persons and to improve utilization of treatment for those infected in the context of injection drug use.