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 was 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 monoinfection, 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 provided a first-time estimate for the absolute and relative risks of clinically signifcant liver disease (cirrhosis, fulminant hepatic failure, and hepatocellular carcinoma) in veteran patients with HCV and HIV moninfection with HCV and dual infection with HCV/HIV.

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External Links for this Project

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PUBLICATIONS:

Journal Articles

1. Giordano TP, Kramer JR, Souchek J, Richardson P, El-Serag HB. Cirrhosis and hepatocellular carcinoma in HIV-infected veterans with and without the hepatitis C virus: a cohort study, 1992-2001. Archives of internal medicine. 2004 Nov 22; 164(21):2349-54. [view]
2. Kramer JR, Giordano TP, Souchek J, El-Serag HB. Hepatitis C coinfection increases the risk of fulminant hepatic failure in patients with HIV in the HAART era. Journal of Hepatology. 2005 Mar 1; 42(3):309-14. [view]
3. Giordano TP, Morgan RO, Kramer JR, Hartman C, Richardson P, White CA, Suarez-Almazor ME, El-Serag HB. Is there a race-based disparity in the survival of veterans with HIV? Journal of general internal medicine. 2006 Jun 1; 21(6):613-7. [view]
4. El-Serag HB, Giordano TP, Kramer J, Richardson P, Souchek J. Survival in hepatitis C and HIV co-infection: a cohort study of hospitalized veterans. Clinical Gastroenterology and Hepatology. 2005 Feb 1; 3(2):175-83. [view]
5. 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. The American journal of gastroenterology. 2005 Jan 1; 100(1):56-63. [view]

Conference Presentations

1. White DL, Green LK, Tavakoli-Tabasi S, Kuzniarek J, Ramsey DJ, Sansgiry S, Francis J, El-Serag HB. Higher total serum testosterone level is associated with increased risk of biopsy-confirmed advanced hepatic fibrosis and inflammation but not advanced steatosis in male Veterans with chronic hepatitis C. Poster session presented at: Digestive Disease Week Annual Meeting; 2012 May 19; San Diego, CA. [view]
2. Buscher AB, Davila J, Hartman C, Giordano TP. In virologically suppressed HIV infected patients, 4-and 6-month follow-up intervals do not increase the risk of virologic failure at 12 months, compared to 3-month intervals. Poster session presented at: Digestive Disease Week Annual Meeting; 2012 May 18; San Diego, CA. [view]

DRA: none
DRE: none
Keywords: none
MeSH Terms: none