Clinical Research
Copyright ©The Author(s) 2005. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 7, 2005; 11(37): 5834-5839
Published online Oct 7, 2005. doi: 10.3748/wjg.v11.i37.5834
Association between thrombotic risk factors and extent of fibrosis in patients with non-alcoholic fatty liver diseases
N Assy, I Bekirov, Y Mejritsky, L Solomon, S Szvalb, O Hussein
N Assy, O Hussein, Liver Unit and Internal Medicine A, Sieff Hospital, Safed, Israel
I Bekirov, Y Mejritsky, Liver Unit and Internal Medicine B, Sieff Hospital, Safed, Israel
L Solomon, Department of Hematology, Sieff Hospital, Safed, Israel
S Szvalb, Department of Pathology, Sieff Hospital, Safed, Israel
N Assy, O Hussein, Technion Faculty of Medicine, Haifa, Israel
Author contributions: All authors contributed equally to the work.
Correspondence to: N Assy, MD, Liver Unit, Sieff Government Hospital, Safed 13100, Israel.
Telephone: +972-4-6828581 Fax: +972-4-6828944
Received: November 15, 2004
Revised: December 3, 2004
Accepted: December 8, 2004
Published online: October 7, 2005

AIM: To evaluate the prevalence of genetic and acquired prothrombotic risk factors and their association with the extent of fibrosis and fatty infiltration in patients with non-alcoholic fatty liver disease (NAFLD).

METHODS: Forty-four patients with chronic hepatitis (28 men and 16 women, with mean age of 4511 and 4912 years, respectively) constituted the patient population of this study. The groups were divided as follows: 15 patients with fatty liver (FL); 15 with non-alcoholic steatohepatitis (NASH); 14 with chronic viral hepatitis (CH) diagnosed by histology and liver technetium scan or ultrasound; and 10 healthy individuals. Thrombophilic, coagulation factors and genetic mutations were diagnosed by standard hemostatic and molecular coagulation assays.

RESULTS: Activated protein C (APC) resistance and protein S were the most prevalent thrombotic risk factors (6% and 10% in NAFLD vs 21% and 14% in CH; P < 0.01 and P < 0.05, respectively). One thrombotic risk factor was identified in 41% of patients (23% mild fibrosis, 18% severe fibrosis) and two thrombotic risk factors in 6% of patients with NAFLD and severe fibrosis. While no differences in APC ratio, lupus anticoagulant, fibrinogen, factor V Leiden, prothrombin, and MTHFR mutation were found. Protein S levels were significantly lower in NASH patients than in patients with FL alone (9219 vs 1062, P < 0.01). Protein C levels were markedly higher in patients with NAFLD and mild or severe fibrosis as compared to the patients with CH, respectively (12840 vs 9614, P < 0.001 or 12936 vs 8813, P < 0.01).

CONCLUSION: Up to 46% of patients with NAFLD may have thrombotic risk factors, and the presence of thrombotic risk factors is correlated with the extent of hepatic fibrosis, suggesting a crucial role of the coagulation system in the pathogenesis of hepatic fibrosis.

Keywords: NASH, NAFLD, Thrombotic risk factors, Fibrosis, Protein S, Protein C