Nuclear factor B (NF-B) is activated during viral infection and isAn estimated 170 million people worldwide and nearly 4 million people in the United States alone are infected with the hepatitis C virus (HCV). 1,2 Up to 85% of the individuals infected with HCV develop a chronic disease course associated with an increased risk of cirrhosis and hepatocellular carcinoma. 1,3 Currently, end-stage liver disease secondary to HCV infection is the leading indication for orthotopic liver transplantation (OLTx) in the United States. 4 Recurrence of HCV infection after OLTx of HCV patients is universal and associated with HCV viremia and high intragraft HCV antigen levels. 5-9 More than half of OLTx patients transplanted because of HCV-related disease will develop histopathologic evidence of chronic hepatitis 10-12 and some will develop a severe form of fibrosing cholestatic hepatitis associated with progressive allograft failure, 13,14 whereas others will develop allograft cirrhosis 15 and de novo hepatocellular carcinoma. 16 The specific pathogenetic mechanisms contributing to recurrent HCV infection and disease progression in immunocompromised transplant patients remain ill defined. Worse yet, the limited understanding of the pathogenesis of HCV infection in immunocompetent individuals provides little insight into the development of a successful therapeutic strategy for transplant recipients infected with the HCV.Substantial evidence has implicated a pivotal role for liver-specific immune-mediated mechanisms that include the production of inflammatory mediators and activation of host effector cells, in the development and progression of the liver injury associated with chronic HCV infection in immunocompetent individuals. [17][18][19][20] Moreover, recent investigations have documented a low number of apoptotic hepatocytes in HCV-infected liver tissue, 21-23 perhaps as a critical mechanism whereby uninhibited viral replication can occur. 24,25 The transcription factor nuclear factor B (NF-B), initially identified as an inducer of B-cell-specific gene expresssion, 26 is known to regulate the HCV-specific expression of several inflammatory mediator genes and inhibition of apoptotic cell death, which may influence the replication of HCV and the

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2016-11-15T19:40:59

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