title: Low-serum testosterone levels pre-liver transplantation are associated with reduced rates of early acute allograft rejection in men.
abstract: BACKGROUND
  Low pretransplant serum testosterone has recently been associated with increased mortality in men awaiting liver transplantation, but the potential impact on rejection has not yet been investigated.
  
  
  METHODS
  Pretransplantation serum testosterone, SHBG, and other variables were collected on 190 consecutive men who received a liver transplant between 2007 and 2013. Rates of subsequent acute cellular rejection were recorded. Multivariable analysis was performed to define variables associated with rejection and other clinically important end points.
  
  
  RESULTS
  Thirty (16%) of 190 men experienced acute cellular rejection. Lower pretransplant testosterone was associated with lower rejection rates, -7% (95% confidence interval [CI], -2% to -12%) per nmol/L decrease in total testosterone and -4% (95% CI, -0.5% to -7%) per 10 pmol/L decrease in free testosterone. Total testosterone (correlation 0.29, P=0.04) and free testosterone (correlation 0.37, P=0.01) correlated significantly with the histological severity of rejection. Older age at transplant (+5% [95% CI, 9%-2%]) per year, and nonautoimmune etiology of liver disease (OR, 1.0 for autoimmune, 0.22 [95% CI, 0.07-0.73] for hepatitis C virus, and 0.58 [95% CI, 0.21-1.71] for other etiologies) were also associated with decreased rejection risk. In a generalized linear model including the covariates testosterone, SHBG, age, etiology, and MELD, total testosterone remained a significant predictor of rejection (adjusted OR, 1.06; P=0.03), as did age at transplant (OR, 0.95; P=0.01).
  
  
  CONCLUSIONS
  Low preliver transplant serum testosterone independently predicts a decreased risk of acute allograft rejection. Whether testosterone is a marker of disease-associated immune dysfunction or has immune-modulatory effects requires further study.
authors.affiliation: 1 Victorian Liver Transplant Unit, Austin Health, Heidelberg, Victoria, Australia. 2 Department of Medicine, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia. 3 Endocrine Unit, Austin Health, Heidelberg, Victoria, Australia. 4 Address correspondence to: Marie Sinclair, Liver Transplant Unit, Austin Health, 145 Studley Road, Heidelberg, Victoria, Australia 3084.
authors.forename: Marie
authors.initials: M
authors.lastname: Sinclair
authors.forename: Peter W
authors.initials: PW
authors.lastname: Angus
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Gow
authors.forename: Rudolf
authors.initials: R
authors.lastname: Hoermann
authors.forename: Tamara
authors.initials: T
authors.lastname: Mogilevski
authors.forename: Mathis
authors.initials: M
authors.lastname: Grossmann
mesh_terms: D000328:Adult; D064591:Allografts; D015415:Biomarkers / Q000097:blood; D016208:Databases, Factual; D058625:End Stage Liver Disease / Q000097:blood* / Q000601:surgery; D006084:Graft Rejection / Q000097:blood*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007902:Length of Stay; D008099:Liver / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012720:Severity of Illness Index; D013739:Testosterone / Q000097:blood*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D013739:Testosterone