BACKGROUND: Recurrent hepatitis C virus (HCV) infection is particularly aggressive in the post liver transplantation setting, with rapid progression of liver fibrosis. Platelet-derived growth factor (PDGF) is reportedly involved in the pathogenesis of liver fibrosis. The aim of this study was to evaluate the possible contribution of molecular variants of the PDGF-B gene to recurrent HCV infection after liver transplantation. METHODS: DNA was extracted from peripheral blood mononuclear cells of 40 patients who underwent liver transplantation for chronic HCV infection and genotyped for polymorphisms in PDGF-B at positions +1135 (A to C) and +286 (A to G). Intrahepatic PDGF-B expression was detected by immunohistochemistry and assessed semiquantitatively. Forty-seven healthy individuals served as controls. RESULTS: Recurrent HCV infection occurred in 34 patients (85%) after a median interval of 10.5 months (range 1.5-60.0). A statistically significant difference was observed in the distribution of the PDGF-B gene polymorphism at position +1135, but not +286 between patients and controls (P=0.05). The A/A genotype occurred at a highly significantly increased rate in patients with recurrent HCV infection than in those without (64.7% vs. 16.67%, P=0.0001), and in patients with severe than in those with nonsevere recurrence (100% vs. 53.85%, P=0.05). The expression level of intrahepatic PDGF-B was found to be highly correlated with the fibrosis stage (P<0.0001). Further analysis yielded a highly statistically significant relationship between the PDGF-B gene polymorphism at position +1135 and clinical parameters of disease severity. CONCLUSIONS: PDGF-B gene polymorphism appears to be associated with severe recurrent HCV infection after liver transplantation. PDGF-B may play an essential role in the development and progression of hepatic fibrosis. These findings, if confirmed, may have important therapeutic implications.
BACKGROUND: Recurrent hepatitis C virus (HCV) infection is particularly aggressive in the post liver transplantation setting, with rapid progression of liver fibrosis. Platelet-derived growth factor (PDGF) is reportedly involved in the pathogenesis of liver fibrosis. The aim of this study was to evaluate the possible contribution of molecular variants of the PDGF-B gene to recurrent HCV infection after liver transplantation. METHODS: DNA was extracted from peripheral blood mononuclear cells of 40 patients who underwent liver transplantation for chronic HCV infection and genotyped for polymorphisms in PDGF-B at positions +1135 (A to C) and +286 (A to G). Intrahepatic PDGF-B expression was detected by immunohistochemistry and assessed semiquantitatively. Forty-seven healthy individuals served as controls. RESULTS: Recurrent HCV infection occurred in 34 patients (85%) after a median interval of 10.5 months (range 1.5-60.0). A statistically significant difference was observed in the distribution of the PDGF-B gene polymorphism at position +1135, but not +286 between patients and controls (P=0.05). The A/A genotype occurred at a highly significantly increased rate in patients with recurrent HCV infection than in those without (64.7% vs. 16.67%, P=0.0001), and in patients with severe than in those with nonsevere recurrence (100% vs. 53.85%, P=0.05). The expression level of intrahepatic PDGF-B was found to be highly correlated with the fibrosis stage (P<0.0001). Further analysis yielded a highly statistically significant relationship between the PDGF-B gene polymorphism at position +1135 and clinical parameters of disease severity. CONCLUSIONS:PDGF-B gene polymorphism appears to be associated with severe recurrent HCV infection after liver transplantation. PDGF-B may play an essential role in the development and progression of hepatic fibrosis. These findings, if confirmed, may have important therapeutic implications.
Authors: Venkata Muddana; James Park; Janette Lamb; Dhiraj Yadav; Georgios I Papachristou; Robert H Hawes; Randall Brand; Adam Slivka; David C Whitcomb Journal: Pancreas Date: 2010-11 Impact factor: 3.327