title: YKL-40-gene polymorphism affects acute cellular rejection and fibrosis progression after transplantation for hepatitis C virus-induced liver disease.
abstract: OBJECTIVE
  The development of end-stage graft disease is suspected to be partially determined by an individual genetic background. The aim of our study was to determine the prevalence of YKL-40-gene polymorphism in hepatitis C virus (HCV)-positive patients and its impact on the incidence of acute cellular rejection (ACR), graft fibrosis and antiviral treatment response.
  
  
  METHODS
  A total of 149 patients, who underwent liver transplantation for HCV-induced liver disease, were genotyped for YKL-40 (rs4950928; G/C) by TaqMan Genotyping Assay. The results were correlated with 616 post-transplant graft biopsies regarding inflammation, fibrosis and evidence for ACR.
  
  
  RESULTS
  No association of YKL-40-genotypes was observed regarding mean inflammation grade (P = 0.216) and antiviral treatment outcome (P = 0.733). However, the development of advanced fibrosis (F3-4) was significantly faster in patients with YKL-40-G-allele: t(CC) = 4.6 versus t(CG/GG) = 2.4 years; P = 0.006. Patients with lower fibrosis (F0-2) compared to advanced fibrosis (F3-4) received significantly more frequent dual immunosuppression (calcineurin inhibitors [CNIs]/mofetile mycophenolate [MMF] vs CNIs; P = 0.003). ACR-occurrence was associated with YKL-40-genotypes (ACR: CC = 60.4%, CG = 25.0% and GG = 14.6% vs non-ACR: CC = 74.2%, CG = 23.8% and GG = 2.0%; P = 0.009) and with gender compatibility between donor and recipient (P = 0.012).
  
  
  CONCLUSIONS
  Fibrosis progression and ACR-incidence after transplantation for HCV-induced liver disease seem to be under genetic control. The negative impact of G-allele on post-transplant events observed in our study, deserves attention and should be verified in larger liver transplantation-cohorts.
authors.affiliation: General, Visceral and Transplantation Surgery, Charité Campus Virchow, Berlin, Germany. dennis.eurich@charite.de
authors.forename: Dennis
authors.initials: D
authors.lastname: Eurich
authors.forename: Ulf P
authors.initials: UP
authors.lastname: Neumann
authors.forename: Sabine
authors.initials: S
authors.lastname: Boas-Knoop
authors.forename: Ruth
authors.initials: R
authors.lastname: Neuhaus
authors.forename: Anja
authors.initials: A
authors.lastname: Kiessling
authors.forename: Ali
authors.initials: A
authors.lastname: Yahyazadeh
authors.forename: Christian
authors.initials: C
authors.lastname: Trautwein
authors.forename: Hermann
authors.initials: H
authors.lastname: Wasmuth
authors.forename: Gero
authors.initials: G
authors.lastname: Puhl
authors.forename: Peter
authors.initials: P
authors.lastname: Neuhaus
authors.forename: Marcus
authors.initials: M
authors.lastname: Bahra
mesh_terms: D054392:Adipokines / Q000235:genetics*; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D000071451:Chitinase-3-Like Protein 1; D016572:Cyclosporine / Q000627:therapeutic use; D018450:Disease Progression; D004359:Drug Therapy, Combination; D058625:End Stage Liver Disease / Q000601:surgery / Q000821:virology*; D005260:Female; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D016174:Hepacivirus; D006526:Hepatitis C / Q000150:complications / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D037102:Lectins / Q000235:genetics*; D008103:Liver Cirrhosis / Q000235:genetics* / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D012737:Sex Factors; D018709:Statistics, Nonparametric; D016559:Tacrolimus / Q000627:therapeutic use; D013997:Time Factors; D055815:Young Adult
chemical_list: D054392:Adipokines; D000998:Antiviral Agents; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D007166:Immunosuppressive Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D037102:Lectins; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D016572:Cyclosporine; C417083:peginterferon alfa-2b; D009173:Mycophenolic Acid; D016559:Tacrolimus