The natural history of hepatitis C virus infection - Host, viral, and environmental factors

Context Hepatitis C virus (HCV) infection may resolve (viral clearance), pe rsist without complications, or cause end-stage liver disease (ESLD), The f requency and determinants of these outcomes are poorly understood. Objective To assess the incidence and determinants of viral clearance and E SLD 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 i njection drug use and an HCV antibody-positive test result during follow-up . Main outcome Measures Viral clearance was assessed in a subset of 919 patie nts and defined as failure to detect HCV RNA in at least 2 consecutive samp les collected 5 or more months apart. End-stage liver disease was assessed at semiannual visits and by review of medical records and death certificate s and defined by the presence of ascites, esophageal varices, or hepatic en cephalopathy, or when ESLD was stated as a cause of death. Results Viral clearance was observed in 90 persons who were compared with 7 22 with persistent viremia, while the viremia of 107 was not resolved. Vira l clearance occurred more often in nonblacks (adjusted odds ratio [OR], 5.1 5; 95% confidence interval [CI], 2.60-10.17) and those not infected with hu man immunodeficiency virus (HIV) (adjusted OR, 2.19; 95% CI, 1.26-3.47). Fo rty cases of ESLD were observed throughout follow-up (incidence, 3.1 per 10 00 person-years). In a multivariate model, risk of ESLD was higher for pers ons 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 alcoh ol 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-li mited or associated with ESLD, the majority of adults have persistent virem ia without clinically demonstrable liver disease. Further research is neede d to explain the less frequent clearance of HCV infection among black perso ns and to improve utilization of treatment for those infected in the contex t of injection drug use.