FGL2/Fibroleukin and Hepatitis C Virus Recurrence Post Liver Transplantation

FGL2/Fibroleukin and Hepatitis C Virus Infection: A Predictor of HCV Recurrence and Progression Post Liver Transplantation

The main objective of this study is to assess whether a recently-developed bioassay for the molecule "secreted fibrinogen-like protein 2" (sFGL2) can be used to predict the recurrence and/or progression of Hepatitis C Virus disease in post liver transplant patients. The hypothesis is that patients with chronic HCV have higher than normal levels of sFGL2 in their blood both pre- and post-transplantation and that this will inhibit their ability to clear HCV, and influence the progression of HCV disease when it recurs.

Study Overview

• Status: Unknown
• Conditions: Liver Transplantation; Hepatitis C

Detailed Description

Hepatitis C Virus infection (HCV) is a serious health problem worldwide, accounting for significant morbidity and mortality. The current treatment, combination therapy with pegylated IFNa/ribavirin results in only a 50% sustained viral response such that HCV is now the leading indication for liver transplantation. Unfortunately, HCV recurrence post-transplantation is universal and it is often difficult to distinguish recurrent HCV from other processes such as rejection, leading to inappropriate or delayed treatment(s) and compounding graft damage. It would be beneficial to have access to a circulating biomarker to distinguish HCV disease recurrence from other processes and to predict the severity of HCV disease progression post-transplantation.

The molecule FGL2 is secreted by cells of the immune system and may be a key immunomodulator affecting graft survival and HCV recurrence. The aim of this study is to assess whether a bioassay for FGL2 can predict HCV disease recurrence and progression after liver transplantation and/or differentiate HCV disease recurrence from acute cellular rejection.

This study will also examine the form of Fc Receptor expressed in these patients. The Fc receptor is hypothesized to be the binding partner of FGL2.

• Study Type: Observational
• Enrollment (Anticipated): 70

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2N2
      • Toronto General Hospital (University Health Network)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Individuals undergoing liver transplantation due to end-stage liver disease caused by Hepatitis C Virus or alcoholic cirrhosis

Description

For HCV positive subjects:

Inclusion Criteria:

1. Able and willing to give written informed consent
2. Willing to follow the study protocol
3. Diagnosis of chronic HCV infection based on two positive serology tests
4. No history of active alcohol or drug abuse
5. All six viral genotypes are considered
6. Pre- and post transplant viral load data must be available

Exclusion Criteria:

1. Pregnancy
2. HBV, HDV or HIV co-infection

For Non-HCV subjects:

Inclusion Criteria:

1. Able and willing to give written informed consent
2. Willing to follow the study protocol

Exclusion Criteria:

1. Free from infection by any of the following: HCV, HBV, HDV or HIV.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
1; Patients undergoing liver transplant for end-stage liver disease due to Hepatitis C
2; Control population: Patients undergoing liver transplantation for end-stage liver disease due to alcoholic cirrhosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
serum FGL2 levels	various time points

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Gary Levy, MD, University Health Network, Toronto

Publications and helpful links

General Publications

• Shalev I, Liu H, Koscik C, Bartczak A, Javadi M, Wong KM, Maknojia A, He W, Liu MF, Diao J, Winter E, Manuel J, McCarthy D, Cattral M, Gommerman J, Clark DA, Phillips MJ, Gorczynski RR, Zhang L, Downey G, Grant D, Cybulsky MI, Levy G. Targeted deletion of fgl2 leads to impaired regulatory T cell activity and development of autoimmune glomerulonephritis. J Immunol. 2008 Jan 1;180(1):249-60. doi: 10.4049/jimmunol.180.1.249.
• Liu H, Zhang L, Cybulsky M, Gorczynski R, Crookshank J, Manuel J, Grant D, Levy G. Identification of the receptor for FGL2 and implications for susceptibility to mouse hepatitis virus (MHV-3)-induced fulminant hepatitis. Adv Exp Med Biol. 2006;581:421-5. doi: 10.1007/978-0-387-33012-9_76. No abstract available.
• Chan CW, Kay LS, Khadaroo RG, Chan MW, Lakatoo S, Young KJ, Zhang L, Gorczynski RM, Cattral M, Rotstein O, Levy GA. Soluble fibrinogen-like protein 2/fibroleukin exhibits immunosuppressive properties: suppressing T cell proliferation and inhibiting maturation of bone marrow-derived dendritic cells. J Immunol. 2003 Apr 15;170(8):4036-44. doi: 10.4049/jimmunol.170.8.4036.

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Anticipated): December 1, 2014
• Study Completion (Anticipated): December 1, 2014

Study Registration Dates

• First Submitted: June 18, 2008
• First Submitted That Met QC Criteria: June 18, 2008
• First Posted (Estimate): June 19, 2008

Study Record Updates

• Last Update Posted (Estimate): July 25, 2013
• Last Update Submitted That Met QC Criteria: July 24, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Disease Attributes; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Recurrence
• Other Study ID Numbers: 08-0385-T