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

NCT01836718 | Unknown

• 2 other identifiers: MISP-5006413-00099
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatitis C Virus; Liver Transplantation

Keywords

Hepatitis C Virus; Liver Transplantation; Antiviral Therapy; HCV

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• HCV persistence

  Time of Transplantation

• Hepatic Fibrosis

  Time of Transplantation

• Extrahepatic reservoirs

  Time of Transplantation

Study Arms (3)

HCV RNA (-) on anti-viral therapy

Patients undergoing liver transplantation who are documented HCV viral load undetectable while on antiviral therapy

HCV RNA (+) on anti-viral therapy

Patients undergoing liver transplantation who are receiving anti-viral therapy and who have a documented detectable HCV viral load

HCV RNA (+) not on anti-viral therapy

Patients undergoing liver transplantation who are not currently receiving anti-viral therapy and are documented viral load positive will be included and serve as a comparison group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with Chronic Hepatitis C on the Mount Sinai Recanati/Miller Transplantation Institute's Liver Transplant Waiting list may be eligible for participation

You may qualify if:

• 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

You may not qualify if:

• Patients who are co-infected with HIV and/or HBV will not be included

Sponsors & Collaborators

• Schiano, Thomas D., MD: lead
• Merck Sharp & Dohme LLC: collaborator
• Icahn School of Medicine at Mount Sinai: collaborator

Study Sites (1)

Mount Sinai School of Medicine Recanati/Miller Transplantation Institute

New York, New York, 10029, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, serum, liver explant tissue and hilar lymph nodes will be obtained for testing. With subject consent, any unused specimens will be retained indefinitely for use in future research either related or unrelated to this study, which may include genetic testing.

MeSH Terms

Conditions

Hepatitis C

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Study Officials

• Thomas D Schiano, MD

  Mount Sinai School of Medicine Recanati/Miller Transplantation Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2013
• First Posted: April 22, 2013
• Study Start: June 1, 2013
• Primary Completion: December 1, 2017
• Study Completion: June 1, 2018
• Last Updated: January 30, 2017

Record last verified: 2017-01

Locations

US (1)