Hepatitis E in HIV-Infected Patients

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 DESCRIPTION (provided by applicant): Hepatitis E Virus (HEV) is an RNA virus associated that can cause both acute hepatitis and chronic liver disease in those with HIV or following solid organ transplantation. The HIV Solid Organ Transplant Study (HIVTR) is a multicenter cohort study of HIV-infected adults who received liver and/or kidney transplantation. HCVRES and HEPRO are NIH Cohort Studies that collected data and samples on HIV-HCV infected patients and HCV controls. A total of 589 HIV infected patients plus non-HIV controls will be evaluated for HEV infection. Preliminary data in the HIVTR cohort demonstrates that prior to transplant over 20% of subjects had serologic evidence of prior infection and nearly 2% of liver candidates had recent acute infection. This proposal is designed to determine the prevalence, incidence and clinical significance of HEV in the HIV infected persons in the U.S.. Furthermore, we will evaluate immunologic and virologic correlates of chronicity and the association with liver injury. We propose to perform longitudinal evaluation of HEV serologies using a validated assay methodology as well as HEV RNA characterization by real-time PCR. A sensitive HEV ELISPOT assay developed in our laboratory will be employed to evaluate seronegative cases and the relationship to prior infection, incident disease and risk of chronicity. Using the cohort databases we will assess the clinical correlates of HEV infection persistence and clearance. Additionally, the natural history of those with chronic infection will be determined, including risk of progression to cirrhosis, effect on other recurrent viral infections (HBV and HCV), and in the transplant cohort, the risk of graft loss. The anticipated results will inform future surveillance practices in HIV-infected persons.