Assessment of Intrahepatic Hepatitis C Virus (HCV) RNA Levels at the Time of Liver Transplantation

The purpose of this study is to measure intrahepatic HCV RNA levels at the time of liver
transplantation in patients receiving antiviral therapy while on the liver transplant waiting
list. This will eventually be correlated with the degree of hepatic fibrosis present within
different geographic sites in the cirrhotic liver. Tissue samples will be obtained from the
patient's liver explant as well as hilar lymph nodes. Upon the removal of the cirrhotic liver
at the time of transplantation, the explant will be biopsied multiple times in different
segments of the liver and preserved for viral detection studies as well as analysis of the
degree of fibrosis. Peripheral blood mononuclear cells (PBMCs) will be obtained for viral
detection at the time of transplantation. Serum HCV RNA levels will also be obtained at 1
month, 3 months and 6 months post liver transplantation.

Study Hypotheses:

- Virological relapse or non-response is higher is patients with cirrhosis due to failure
of antiviral medication to concentrate adequately in a fibrotic liver having an altered
sinusoidal micro-architecture

- HCV may persist in different geographic regions of the fibrotic liver in part predicated
on blood supply to that area and this may have an effect on overall virological
response. These differences in viral persistence and detection may exist in different
lobes of the liver or even within a few centimeters within the same portion of the liver
parenchyma.

- PBMC and hilar lymph nodes may be extrahepatic reservoirs of HCV viral persistence in
patients receiving antiviral therapy and may account for virological relapse
post-therapy

- There may be varying degrees of fibrosis within the same cirrhotic liver which may
impact on hepatic synthetic function and antiviral response to treatment.