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

Liver Transplantation Clinical Trial

Official title:

An Assessment of Intrahepatic HCV RNA Levels at the Time of Liver Transplantation in Patients With HCV Receiving Antiviral Therapy While on the Liver Transplant Waiting List Compared to Those Not Currently Receiving Therapy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01836718
• Other study ID #: MISP-50064
• Secondary ID: 13-00099
• Status: Active, not recruiting
• Phase: N/A
• First received: April 17, 2013
• Last updated: January 27, 2017
• Start date: June 2013
• Est. completion date: June 2018

Study information

• Verified date: January 2017
• Source: Schiano, Thomas D., MD
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: June 2018
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C Virus
• Liver Transplantation

Locations

Country	Name	City	State
United States	Mount Sinai School of Medicine Recanati/Miller Transplantation Institute	New York	New York

Sponsors (3)

Lead Sponsor	Collaborator
Schiano, Thomas D., MD	Icahn School of Medicine at Mount Sinai, Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HCV RNA PCR levels	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	Time of Transplantation
Secondary	HCV persistence	To ascertain whether HCV persistence within the liver is predictive of virological relapse post liver transplantation.	Time of Transplantation
Secondary	Hepatic Fibrosis	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.	Time of Transplantation
Secondary	Extrahepatic reservoirs	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.	Time of Transplantation