The purpose of this investigation is to evaluate the effect of HIV infection, drug use and other factors on the progression of hepatitis C. The observation of heterogenous outcomes after hepatitis C virus (HCV) infection suggests the hypothesis that viral, genetic, and environmental factors affect disease progression. To examine the relative importance of multiple factors, in a representative setting and with appropriate power, a series of integrated experiments have been designed for specimens from a large cohort (ALIVE) of injecting drug users (IDUs) who have been followed semiannually since 1988. The study population is 1,265 HCV-infected IDUs, including 378 coinfected with HIV at enrollment. By prospectively assessing liver enzymes and actively ascertaining clinical evidence of hepatic failure or death on all participants and evaluating liver biopsies randomly obtained from 210 individuals, an estimated 50 cases of progressive HCV infection will be identified. The effect of HIV infection, drug use, viral heterogeneity, and genetic factors on HCV natural history will be evaluated. Prospective and nested case control analysis will be used to compare the occurrence of putative cofactors among the 50 cases and controls, matched for confounders such as the duration of drug use. After 4 years of rigorous follow-up and reassessment with liver biopsy, the relationship of hepatic histology, liver enzymes, HCV viral load and the clinical expression of disease also will be evaluated. The investigators have experience with all research methods, including assessment of HCV viral load, genotype and quasispecies distribution; HLA haplotype and gene marker characterization; liver biopsy procurement and evaluation; and analytic techniques. Success at minimal expense is likely because the study will utilize a large HCV-infected cohort, an established research setting, eight years of existing data, experienced lab personnel, and superb collaborators.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA010627-05
Application #
6489481
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Davenny, Katherine
Project Start
1998-01-01
Project End
2002-12-31
Budget Start
2002-01-01
Budget End
2002-12-31
Support Year
5
Fiscal Year
2002
Total Cost
$406,266
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Mehta, Shruti H; Brancati, Frederick L; Strathdee, Steffanie A et al. (2003) Hepatitis C virus infection and incident type 2 diabetes. Hepatology 38:50-6
Mehta, Shruti H; Cox, Andrea; Hoover, Donald R et al. (2002) Protection against persistence of hepatitis C. Lancet 359:1478-83
Streiff, Michael B; Mehta, Shruti; Thomas, David L (2002) Peripheral blood count abnormalities among patients with hepatitis C in the United States. Hepatology 35:947-52
Rai, Rudra; Wilson, Lucy E; Astemborski, Jacquie et al. (2002) Severity and correlates of liver disease in hepatitis C virus-infected injection drug users. Hepatology 35:1247-55
Mao, Q; Ray, S C; Laeyendecker, O et al. (2001) Human immunodeficiency virus seroconversion and evolution of the hepatitis C virus quasispecies. J Virol 75:3259-67
Wilson, L E; Umemura, T; Astemborski, J et al. (2001) Dynamics of SEN virus infection among injection drug users. J Infect Dis 184:1315-9
Mehta, S H; Brancati, F L; Sulkowski, M S et al. (2000) Prevalence of type 2 diabetes mellitus among persons with hepatitis C virus infection in the United States. Ann Intern Med 133:592-9
Thomas, D L; Astemborski, J; Vlahov, D et al. (2000) Determinants of the quantity of hepatitis C virus RNA. J Infect Dis 181:844-51
Inglesby, T V; Rai, R; Astemborski, J et al. (1999) A prospective, community-based evaluation of liver enzymes in individuals with hepatitis C after drug use. Hepatology 29:590-6