Clinical trial NCT01836718: Assessment of Intrahepatic Hepatitis C Virus (HCV) RNA Levels at the Time of Liver Transplantation
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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Hepatitis C Virus
Liver Transplantation
Keywords: Hepatitis C Virus
Liver Transplantation
Antiviral Therapy
HCV
Lead sponsor: Schiano, Thomas D., MD
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
name: Icahn School of Medicine at Mount Sinai
First posted: 2013-04-22
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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

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.


Eligibility criteria: 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

Primary outcomes:
measure: HCV RNA PCR levels
timeFrame: Time of Transplantation
Secondary outcomes:
measure: HCV persistence
timeFrame: Time of Transplantation
measure: Hepatic Fibrosis
timeFrame: Time of Transplantation
measure: Extrahepatic reservoirs
timeFrame: Time of Transplantation
Other outcomes:
Locations:
city: New York
country: United States
facility: Mount Sinai School of Medicine Recanati/Miller Transplantation Institute
state: New York
Study officials:
affiliation: Mount Sinai School of Medicine Recanati/Miller Transplantation Institute
name: Thomas D Schiano, MD
role: PRINCIPAL_INVESTIGATOR
References: