Defense Date

2009

Document Type

Thesis

Degree Name

Master of Science

Department

Physiology

First Advisor

Valeria Mas

Abstract

Hepatitis C virus recurrence (which is defined by detection of HCV RNA in serum) in post-transplanted liver is universal but the progression of infection remains unpredictable, varying from case to case. It has been estimated that 75%-80% of the HCV recurrence patients will suffer chronic hepatitis C infection and up to a third of them will progress into the development of fibrosis and cirrhosis within 5 years post-transplantation. Therefore, finding ways to predict early on the progression of fibrosis can contribute to better prognoses. Recent literatures have mentioned that the hepatitis C virus relies on the host microRNA-122 (miR-122) for assistance in replication of the viral genome in hepatocytes. Experimental depletion of miRNA-122 in the cell line Huh 7 has shown up to an 80% decrease in HCV whereas an increase of miRNA-122 has shown an increase of HCV. Since miRNAs are known to have numerous indirect roles by the binding of the target messenger RNAs (mRNAs) and repressing the expression of their proteins, we hypothesized that the elucidation of associations between miRNA-122 and the histological severity in HCV recurrence post-liver transplantation might serve as a biomarker in predicting the outcome of HCV recurrence severity in patients. We also evaluated the expression levels of BCAP31 (a predicted target of miRNA-122), and CD4 (T cell surface molecules involved in immune response) among the HCV recurrence severity groups. RNA samples were isolated from FFPE liver samples from patients with HCV recurrence post-transplantation, and Reverse Transcription and TaqMan Real-Time PCR were carried out for qualitative analysis. We did not see any association between the levels of miRNA-122 expression and severity of HCV recurrence, but we did find a positive correlation between the miRNA-122 expression and the HCV viral load in Group 3 (Severe) at time of HCV recurrence, which supports previous studies of the role of miRNA-122 in HCV replication. We did not find any associations between the expression of BCAP31 and the severity of HCV recurrence but we did discovery an inverse relationship between miRNA-122 and BCAP31 in Group 3 (Severe) at time of HCV recurrence, confirming our assumption of miRNA:mRNA interaction. Also, we did find CD4 expression being statistically significant between Group 1 (Benign) versus Group 3 (Severe), which may support the hypothesis that strong, adequate CD4+ T-cell response is associated with better outcome post-liver transplantation.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

August 2009

Included in

Physiology Commons

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