Defense Date

2011

Document Type

Thesis

Degree Name

Master of Science

Department

Physiology

First Advisor

Valeria Mas

Abstract

Hepatitis C virus (HCV) is the major cause of chronic hepatitis worldwide and a leading cause for liver transplant. Unfortunately, graft HCV infection is a universal phenomenon despite of pre-transplant prophylactic strategies. Acute HCV infection and innate immune responses elicit an inflammatory scenario that triggers the recruitment of adaptive immune response cells. Of those chronically infected, 30% experience accelerated fibrosis with concomitant cirrhosis development within 5 years post-LT and require re-transplant. With many patients responding unfavorably to antivirals and ineffective vaccines, much attention is now placed on T cell immunity in controlling HCV infection. This study represents a retrospective analysis that examined the association of T cells with respect to liver fibrosis severity progression in a prospective cohort of biopsy samples taken from 27 patients at the time of HCV recurrence disease diagnosis post-LT. For those patients, the fibrosis progression was scored 36 months post-LT by Metavir scoring system. Liver biopsies were classified based on fibrosis severity as Mild (G1; n = 12), Moderate (G2; n = 6), and Severe (G3; n = 9). Additionally, an independent set of liver biopsy samples, taken according to fibrosis severity progression, was classified (G1; n =3, G3; n = 4) and used as a validation set for CD4 gene expression. Real time PCR was performed to study the expression of immune-related genes using the Taqman® probe system. From the results analysis, the CD4 T cell marker encoding gene was down-regulated (2.9-fold) in G3 with respect to G1; although, only borderline significant (p = 0.052). This suggests an inverse relationship of CD4+T cell related-genes expression with respect to worse fibrosis progression in HCV recurrence diagnosed recipients. The validation samples showed a similar trend (1.8 fold decrease in G3 with respect to G1), although not significant. This may be due to impaired T cell function resulting from T cell exhaustion, poor dendritic cell priming and activation, or the use of immunosuppressant drugs. To conclude, CD4 could be a potential biomarker to help in identifying HCV recurrent patients with a high risk of fibrosis development soon after LT.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

August 2011

Included in

Physiology Commons

Share

COinS