Clinical trial NCT00701272: FGL2/Fibroleukin and Hepatitis C Virus Recurrence Post Liver Transplantation
Official title: FGL2/Fibroleukin and Hepatitis C Virus Infection: A Predictor of HCV Recurrence and Progression Post Liver Transplantation
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Liver Transplantation
Hepatitis C
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2008-06-19
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: serum FGL2 levels
timeFrame: various time points
Secondary outcomes:
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Toronto General Hospital (University Health Network)
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Gary Levy, MD
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.4049/jimmunol.180.1.249.
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. doi: 10.1007/978-0-387-33012-9_76. No abstract available.
citation: 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.