Hepatitis C virus receptors claudin-1 and occludin after liver transplantation and influence on early viral kinetics

Abstract

Liver transplantation (LT) is a unique model to study hepatitis C virus (HCV) entry into hepatocytes. Recent in vitro studies suggest significant changes in the expression of the HCV receptors claudin‐1 and occludin after HCV infection. Our aims were: (1) to characterize claudin‐1 and occludin expression in grafts from LT recipients and (2) to explore their potential influence on early HCV kinetics and their changes after HCV infection. We included 42 HCV‐infected LT recipients and 19 uninfected controls. Claudin‐1 and occludin were detected in paraffin‐embedded liver biopsies obtained during reperfusion and 3 and 12 months after LT. HCV receptors were characterized by confocal immunofluorescence microscopy; quantification and colocalization studies were performed with dedicated software. Claudin‐1 and occludin expression were restricted to the apical pole of hepatocytes. There was a significant correlation between the amount of scavenger receptor B1 at the time of reperfusion and the HCV‐RNA decay during the first 24 hours following LT (r = 0.55, P = 0.007). Similarly, there was a significant correlation between the levels of claudin and occludin and the slope of HCV‐RNA increase during the first week after LT (r = 0.63, P = 0.005). Occludin and claudin‐1 levels increased significantly 12 months after LT (P = 0.03 and P = 0.007, respectively). The expression pattern of both proteins, however, remained unchanged, colocalizing strongly (60%‐94%) at the apical membrane of hepatocytes. Conclusions. HCV receptor levels at the time of LT seem to modulate early HCV kinetics. Hepatitis C recurrence after LT was associated with increased levels of claudin‐1 and occludin in the hepatocyte cell membrane, although it did not alter their localization within the tight junctions. (HEPATOLOGY 2011;.)