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.

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.