A study of novel biomarkers of hepatitis C related liver injury

Abstract

Chronic hepatitis C virus (HCV) is the most frequent indication for liver transplantation. Unfortunately HCV recurrence is universal following transplantation and many patients will experience aggressive disease recurrence. This thesis comprises 3 related studies with the main focus being an assessment of factors which may impact on the course of HCV recurrence post-transplant. The first study was a retrospective analysis of 118 consecutive HCV-positive liver transplant patients with a median duration of follow-up of 32.4 months. Peak viral RNA ≥ 107 in the first year post-transplant was shown to be an independent predictor of diminished patient survival. The second study was a cross-sectional pilot study using a recently developed CD antibody microarray in patients with various causes for liver disease. This demonstrated disease-specific consensus patterns of expression of CD antigens for patients with chronic liver disease and in particular, the ability to separate major stages of liver disease. In the third study serial CD antigen expression profiles were performed on patients undergoing liver transplantation for HCV infection. Differential antibody expression was most significant in the pre-transplant phase suggesting a significant impact of pre-transplant factors on disease severity post-liver transplantation. The findings in this thesis have demonstrated utility of the CD antibody microarray in the study of human liver disease and have shed light on the importance of post-transplant viral loads in determining the severity of post-transplant HCV recurrence.