Hepatitis C Virus, Liver Transplantation
Conditions
Keywords
Hepatitis C Virus, Liver Transplantation, Antiviral Therapy, HCV
Brief summary
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.
Interventions
None listed
Sponsors
Merck Sharp & Dohme LLC
Icahn School of Medicine at Mount Sinai
Schiano, Thomas D., MD
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients age 18-80 with chronic HCV on the liver transplant waiting list may be eligible for participation * The following subjects will be enrolled: * Patients undergoing liver transplantation who are documented HCV viral load undetectable while on antiviral therapy * Patients receiving anti-viral therapy and who have a detectable HCV viral load * Patients not currently receiving antiviral therapy and are HCV PCR (+) will be included and serve as a comparison group
Exclusion criteria
* Patients who are co-infected with HIV and/or HBV will not be included
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HCV RNA PCR levels | Time of Transplantation | The primary objective is to detect and quantitate HCV RNA PCR levels in different anatomic regions of the liver at the time of liver transplantation to ascertain whether there is similar geographic presence and/or clearance of HCV during antiviral therapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HCV persistence | Time of Transplantation | To ascertain whether HCV persistence within the liver is predictive of virological relapse post liver transplantation. |
| Hepatic Fibrosis | Time of Transplantation | To assess the degree of hepatic fibrosis at the site of intrahepatic HCV viral detection in order to ascertain whether HCV viral detection correlates with the degree of fibrosis. This study will also examine whether there can be different degrees of hepatic fibrosis in different geographic portions of the same liver and whether there would be a correlation with the patients' natural MELD score, degree of hepatic synthetic function and ultimate virological response to antiviral therapy. |
| Extrahepatic reservoirs | Time of Transplantation | To examine whether hilar lymph nodes and PBMC are extrahepatic reservoirs of HCV in patients receiving antiviral therapy and then to correlate this with intrahepatic detection of HCV and overall virological response. |
Countries
United States
Outcome results
None listed