Following liver transplantation, recurrence of the primary pathologic process has been postulated for a number of diseases including primary biliary cirrhosis and primary sclerosing cholangitis. Disease recurrence is a major cause of post-transplant morbidity in patients undergoing transplantation for hepatitis B viral (HBV) infection. Whether graft reinfection occurs with the newly identified hepatitis C virus (HCV) is unknown. Using molecular techniques including Southern analysis and polymerase chain reaction (PCR) to identify viral DNA and RNA in patients transplanted for HBV and HCV respectively, we will examine the prevalence of graft infection, factors predictive of post-transplant recurrence, as well as the effect of immunosuppression on viral replication. The immune system plays a pivotal role both in the clearance of HBV following acute infection, and in hepatic damage resulting from chronic HBV infection. Suppression of the immune system as occurs in the liver transplant recipient frequently leads to aggressive post-transplant hepatitis in patients with prior HBV infection. We propose to study the mechanism by which hepatic damage is mediated in these patients. Specifically, we will examine if serum HBV DNA reflects hepatic viral replication, and whether there is a relationship between HBV DNA and hepatic damage. Cytokines, a family of proteins released by inflammatory cells in, response to infections such as HBV, are both mediators of the host response to initial infection and propagators of immune-mediated damage in chronic infection. Using PCR, we will investigate the local release of cytokines by lymphocytes in the liver of patients with recurrent HBV and correlate cytokine mRNA levels with evidence of hepatic damage. Identification of factors predictive of graft infection with HBV will aid in the pre-transplant selection of patients at lower risk for recurrence. Understanding the mechanism of hepatotoxicity of these viruses and the effects of immunosuppression on viral replication has implications not only for liver transplant recipients, but for all infected patients.
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