Platelet-derived growth factor gene polymorphism in recurrent hepatitis C infection after liver transplantation.
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.
Liver Institute and Department of Medicine D, Rabin Medical Center, Beilinson Campus, Petah Tiqva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. gbenari@bezeqint.net
Ziv
Z
Ben-Ari
Anat R
AR
Tambur
Orit
O
Pappo
Jaqueline
J
Sulkes
Vera
V
Pravica
Ian
I
Hutchinson
Tirza
T
Klein
Ran
R
Tur-Kaspa
Eytan
E
Mor
D005260:Female; D019698:Hepatitis C, Chronic / Q000209:etiology / Q000235:genetics* / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008103:Liver Cirrhosis / Q000150:complications / Q000235:genetics* / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020574:Proto-Oncogene Proteins c-sis / Q000032:analysis / Q000235:genetics*; D012008:Recurrence
D020574:Proto-Oncogene Proteins c-sis