Low-serum testosterone levels pre-liver transplantation are associated with reduced rates of early acute allograft rejection in men.

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).

Conclusion: 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.