title: Association between thrombotic risk factors and extent of fibrosis in patients with non-alcoholic fatty liver diseases.
abstract: OBJECTIVE
  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 45+/-11 and 49+/-12 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 (92+/-19 vs 106+/-2, 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 (128+/-40 vs 96+/-14, P<0.001 or 129+/-36 vs 88+/-13, P<0.01).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Liver Unit, Sieff Government Hospital, Safed 13100, Israel. assy.n@ziv.health.gov.il
authors.forename: N
authors.initials: N
authors.lastname: Assy
authors.forename: I
authors.initials: I
authors.lastname: Bekirov
authors.forename: Y
authors.initials: Y
authors.lastname: Mejritsky
authors.forename: L
authors.initials: L
authors.lastname: Solomon
authors.forename: S
authors.initials: S
authors.lastname: Szvalb
authors.forename: O
authors.initials: O
authors.lastname: Hussein
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000378:metabolism; D001779:Blood Coagulation Factors / Q000378:metabolism; D005234:Fatty Liver / Q000473:pathology*; D005260:Female; D005355:Fibrosis / Q000473:pathology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D011486:Protein C / Q000378:metabolism; D017293:Protein S / Q000378:metabolism; D012307:Risk Factors; D013927:Thrombosis / Q000473:pathology*
chemical_list: D000925:Anticoagulants; D001779:Blood Coagulation Factors; D011486:Protein C; D017293:Protein S