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

Observational Study

Yandi Huang et al. BMC Gastroenterol. 2021.

Abstract

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.

Keywords: Acute-on-chronic liver failure; Androgen; Hepatitis B; Testosterone.

© 2021. The Author(s).

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Conflict of interest statement

The authors declare that they have no competing interest.

Figures

Fig. 1

Fig. 1

Box plot illustrating androgens in survivor and patients who experienced the composite outcome of death or transplant. The composite outcome (n = 55) was associated with lower total testosterone (P < 0.001, A), sex-hormone-binding globulin (P < 0.001, B), free testosterone index (P = 0.032, C) and higher cortisol (P = 0.007, E), androstenedione (P = 0.038, F) compared with those survived without transplant (n = 105). The dehydroepiandrosterone sulfate level was similar among those two groups (P = 0.686, D). TT total testosterone, SHBG sex-hormone-binding globulin, FTI free testosterone index, DHEAS dehydroepiandrosterone sulfate, AND androstenedione, SQRT Square Root

Fig. 2

Fig. 2

Kaplan–Meier survival curves for cases of hepatitis B virus-related acute-on-chronic liver failure. A Transplant-free survival without composite endpoint was lower among men with total testosterone levels below the cutoff of 142.39 ng/dL than among those with total testosterone levels above the cutoff value within 90 days. B Transplant-free survival without death was lower among men with total testosterone levels below the cutoff of 142.39 ng/dL than among those with total testosterone levels above the cutoff value within 90 days

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