Lower testosterone levels predict increasing severity and worse outcomes of hepatitis B virus-related acute-on-chronic liver failure in males

BACKGROUND: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a serious liver disease with pathogenesis remaining unclear. This study aims to investigate the association between testosterone levels, stage (early, middle, or late, categorized according to clinical manifestation), severity scores, and clinical outcomes of HBV-ACLF. METHODS: This single-center observational study involved 160 male patients with HBV-ACLF, 151 chronic hepatitis B patients without liver failure (CHB) and 106 healthy controls (HC). Morning blood samples were collected and androgen levels analyzed by chemi-bioluminescent immunoassay. Time to death or liver transplantation within 90 days comprised the primary composite outcome. RESULTS: Serum levels of total testosterone (TT), free testosterone index (FTI), dehydroepiandrosterone sulfate and cortisol were significantly lower among HBV-ACLF than CHB and HC, while androstenedione was higher. Low TT, sex hormone binding globulin and FTI were associated with increased stage (of HBV-ACLF, ascites, and hepatic encephalopathy) and severity scores (Model for End-stage Liver Disease and Chinese Group on the Study of Severe Hepatitis B-ACLF scores). Low TT (< 142.39 ng/dL) was a risk factor for both the composite outcome and for death alone within 90 days. Multivariate analysis revealed TT to be an independent predictor for the composite outcome (hazard ratio 2.57, 95% CI 1.09–6.02; P = 0.030). CONCLUSION: Low serum testosterone is common among male patients with HBV-ACLF and predictive of increased severity and worse outcome of the disease and may play an important role in the progression of HBV-ACLF.