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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:https://doi.org/10.1001/jama.284.4.450
Author Affiliations: Departments of Medicine (Drs Thomas, Rai, Anania, Nelson, Wilson, and Vlahov, Mss Astemborski and Nolt, and Mr Laeyendecker), Epidemiology (Drs Thomas, Galai, Nelson, Strathdee, and Vlahov, Mss Schaeffer and Johnson), and Pathology (Dr Boitnott), Johns Hopkins Medical Institutions, Baltimore, Md.
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
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