Expression pattern of molecular chaperones after liver transplantation in hepatitis C positive recipients. Relation to serum HCV-RNA titers

Abstract

Hepatitis C (HCV) is one of the main causes of liver transplantation (OLT). Previously we have reported that high serum C RNA level correlates with the severity of histopathological signs and poor clinical outcome. The core antigen of virus C is known to interfere with chaperones in the hepatocytes, results in an endoplasmic reticulum (ER) stress. In this study HCV positive liver transplanted patients were evaluated, whether there are correlations among chaperone expression, recurrence and viral titer. Patients were enrolled after surviving the first month following OLT. Sera were collected regularly, and biopsies were taken on demand following OLT. The diagnosis of recurrent HCV was proven by Knodell-Ishak scoring. In this case ribavirin+interferon were initiated, and maintained for one year. All chaperones were upregulated in the transplanted liver graft showing recurrent hepatitis C disease. ATF6, GP96, GRP78, CNX and CLR chaperones were upregulated significantly compared to their levels in normal livers. Except for one chaperone, the level of upregulation did not correlate with the serum's HCV-RNA titre: the only difference between Group1 and 2 (RNA titre above and below 8.78 106 respectively) was that the level of ATF6 was 1.6 times higher in Group1 compared to Group2. The expression of all chaperones was reduced, and some even became downregulated after the interferon treatment. In accordance with the literature our results suggest that hepatitis C might induce apoptosis through ER-stress. Those cells exposed to a high C viral load, had a lower chance to be eliminated.