FGL2/Fibroleukin and Hepatitis C Virus Recurrence Post Liver Transplantation

Hepatitis C Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT00701272
• Other study ID #: 08-0385-T
• Status: Enrolling by invitation
• Phase: N/A
• First received: June 18, 2008
• Last updated: July 24, 2013
• Start date: June 2008
• Est. completion date: December 2014

Study information

• Verified date: July 2013
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 70
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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 Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Liver Transplantation

Locations

Country	Name	City	State
Canada	Toronto General Hospital (University Health Network)	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	serum FGL2 levels		various time points	No