title: Factor XIII Val34Leu mutation accelerates the development of fibrosis in patients with chronic hepatitis B and C.
abstract: OBJECTIVE
  There is considerable variation in liver fibrosis stage and progression to cirrhosis among patients with chronic hepatitis B (CHB) or C (CHC). Coagulation pathway activity due to genetic variations could influence the rate of fibrosis. We investigated thrombotic risk factors and their association with the extent and progression of fibrosis in CHB or CHC patients.
  
  
  METHODS
  In total, 194 patients with CHB (n = 88) or CHC (n = 106) were included. Data on demographic and laboratory findings were collected. Liver biopsies were evaluated according to the Ishak classification system. Fibrosis progression rate (FPR), defined as ratio of fibrosis score to duration of infection, was determined for 131 patients. Prevalence of factor V Leiden, prothrombin G20210A, plasminogen activator inhibitor type-1 (PAI-1) 4G/5G and factor XIIIA Val34Leu mutations was evaluated.
  
  
  RESULTS
  Heterozygosity for factor V Leiden, prothrombin G20210A, PAI-1 4G/5G and factor XIIIA Val34Leu mutations was present in 3.1%, 2.1%, 49% and 28% of the patients, respectively. Factor XIII Val34Leu mutation was a risk for enhanced FPR (odds ratio 4.7; P = 0.01). In patients with both factor XIII Val34Leu and PAI-1 4G/5G mutations the risk of an accelerated FPR was further increased (odds ratio 5.0; P = 0.02). Mutations of the other thrombotic genes were not significantly associated with fibrosis stage and FPR.
  
  
  CONCLUSIONS
  Our data show that factor XIII Val34Leu mutation alone or in combination with PAI-1 4G/5G mutation is a risk factor for an increased rate of liver fibrosis development in patients with CHB or CHC.
authors.affiliation: Department of Internal Medicine             Department of Gastroenterology and Hepatology             Department of Pathology             Department of Experimental Immunology             Clinical Research Unit             Department of Vascular Medicine             Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands             Department of Paediatrics, University of Oxford, Oxford, UK             HIV Pathogenesis Program, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Kathelijne
authors.initials: K
authors.lastname: Dik
authors.forename: Joep
authors.initials: J
authors.lastname: de Bruijne
authors.forename: R Bart
authors.initials: RB
authors.lastname: Takkenberg
authors.forename: Joris J
authors.initials: JJ
authors.lastname: Roelofs
authors.forename: Marjan J
authors.initials: MJ
authors.lastname: Tempelmans
authors.forename: Marcel G W
authors.initials: MG
authors.lastname: Dijkgraaf
authors.forename: Huub C
authors.initials: HC
authors.lastname: Gelderblom
authors.forename: Henk W
authors.initials: HW
authors.lastname: Reesink
authors.forename: Joost C M
authors.initials: JC
authors.lastname: Meijers
authors.forename: Peter L
authors.initials: PL
authors.lastname: Jansen
authors.forename: Marcel
authors.initials: M
authors.lastname: Levi