BACKGROUND/RATIONALE:
It is estimated that approximately a quarter of a million patients in the United States have a dual infection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) and this prevalence is expected to increase due to the improved survival of HIV-infected patients. Veterans have been disproportionately affected by HCV with reported prevalence rates ranging from 5% to 35%, resulting in a substantial increase in the rates for liver disease in the VA system.
OBJECTIVE(S):
Specific Aim #1 Compare the incidence rates of three separate liver disease outcomes (acute liver failure, cirrhosis and hepatocellular carcinoma) between the dual HCV-HIV infection cohort and each of the HCV monoinfection cohort or the HIV monoinfection cohort, while adjusting for the presence of risk factors for liver disease (e.g. demographic features, other viral hepatitis, alcoholic cirrhosis), and other potential confounders (e.g. health resource use, psychiatric disorders including alcohol and drug use).
Specific Aim #2 Compare the overall mortality rates between the dual HCV-HIV infection cohort and each of the HCV monoinfection cohort or the HIV monoinfection cohort, while adjusting for demographic features, comorbid disease severity of HIV and non-HIV related disorders, HIV therapy (HAART), and other potential confounders (e.g. health resource use, psychiatric disorders including alcohol and drug use).
METHODS:
This is a retrospective cohort study in US veterans using information collected in several national VA databases.
The three study cohorts were identified from all patients hospitalized between 10/1992 and 10/2000 with HCV or HIV. Inception time for follow up was defined by the date of the first hospitalization with either infection. Patients with liver disease recorded prior to the inception date were excluded. We identified 13,368 patients with HIV monoinfection, 36,126 with HCV monoinfection, and 5,068 patients with dual HCV HIV infection.
To further characterize the study cohorts and to collect data on outcomes and covariates, information will be collected from VA databases including the PTF, Outpatient files and the Beneficiary Identification and Records Locator Subsystem Death File.
FINDINGS/RESULTS:
We identified 11,678 veterans with HIV moninfection, 26,641 veterans with HCV monoinfection, and 4761veterans with dual HCV/HIV infection between 1991 and 2000 who fulfilled the inclusion and exclusion criteria. We examined the incidence of cirrhosis, and HCC among these three cohorts. Incidence rates, cumulative incidence, and Cox proportional hazard ratios were calculated. We recorded our findings in five manuscripts (4 published, and one submitted) all attached in the appendix. For example (publication #1) , as compared to HCV moninfection, we found dual infection to be a significant risk factor for cirrhosis during the pre-HAART era but it was not associated with hepatocellular carcinoma, irrespective of time period. There was an increased risk of cirrhosis in patients with coinfection during the pre-HAART era (before 10/1996) (hazard ratio=1.48, p=0.02), but not among patients who entered the cohort during the HAART era. The unadjusted incidence rate of hepatocellular carcinoma in patients with coinfection and HCV-only was 1.3 and 2.0/1000 person-years, respectively (p=0.04). In the multivariate model, coinfection was not associated with hepatocellular carcinoma (hazard ratio=0.84, p=0.40).
IMPACT:
Our studies provide a first-time estimate for the absolute and relative risks of clinically signifcant liver disease in patients with HCV and HIV moninfection and dual infection.
PUBLICATIONS:
Journal Articles
- Giordano TP, Visnegarwala F, White AC, Troisi CL, Frankowski RF, Hartman CM, Grimes RM. Patients referred to an urban HIV clinic frequently fail to establish care: factors predicting failure. AIDS Care. 2005; 17(6): 773-83.
- Shelburne SA, Visnegarwala F, Darcourt J, Graviss EA, Giordano TP, White AC, Hamill RJ. Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy. AIDS. 2005; 19(4): 399-406.
- Kramer JR, Giordano TP, Souchek J, Richardson P, Hwang LY, El-Serag HB. The effect of HIV coinfection on the risk of cirrhosis and hepatocellular carcinoma in U.S. veterans with hepatitis C. American Journal of Gastroenterology. 2005; 100(1): 56-63.
