Testosterone and Estradiol as Novel Prognostic Indicators for HBV-Related Acute-on-Chronic Liver Failure

Abstract

Background: HBV-related acute-on-chronic liver failure (HBV-ACLF) has a high short-term mortality and urgently needs an early warning system with simplicity and high accuracy. Previous studies show that sex hormones play potential roles in the progression of HBV-related liver diseases.Aims: To explore the effect of testosterone and estradiol on the occurrence and prognosis of HBV-ACLF.Methods: A prospective cohort of 300 chronic hepatitis B (CHB) patients was enrolled among which 108 were diagnosed with HBV-ACLF at admission and 20 developed to HBV-ACLF during hospitalization. We compared the level of serum testosterone and estradiol of patients with varied ACLF background, disease severity and cirrhosis conditions and analyzed the predictive ability of short-term prognosis. A novel prognostic model involving testosterone was developed and further validated in the HBV-ACLF group.Results: The baseline estradiol level of HBV-ACLF group was significantly higher while testosterone was lower than that of non-ACLF group. The estradiol level increased while the testosterone level decreased as the number of organ failures increased. Testosterone had high accuracy in predicting the short-term mortality in HBV-ACLF (AUROC = 0.726) and estradiol did better in predicting the occurrence of ACLF during hospitalization (AUROC = 0.695). The novel prognostic model involving testosterone (TATIM model) was proved to have considerable prediction efficiency in HBV-ACLF cohort with or without cirrhosis.Conclusion: Testosterone could be utilized as short-term prognostic indicator for HBV-related ACLF and estradiol can help to predict its occurrence. TATIM model is a novel prognostic model for HBV-related ACLF with simplicity and good performance irrespectively of liver cirrhosis.Clinical Trial Registration Number: This study was based on a sub-cohort from the prospective multicenter cohort (NCT02457637).

DHEA and Its Metabolites Reduce the Cytokines Involved in the Inflammatory Response and Fibrosis in Primary Biliary Cholangitis

“…In PBC patients under 40, the level of estrogen (E2) was below the reference range for fertile women. As reported earlier, low levels of estradiol [ 30 ] or testosterone [ 31 , 32 ] could predict mortality in chronic liver diseases. In addition, we found that the level of DHEA in both younger and older PBC patients was still within the reference range for healthy females.…”

The immune and metabolic treatment approach of using testosterone on mice models of liver injury

“…Several studies have shown a relationship between testosterone and liver injury ( Al-Qudimat et al, 2021 ). Even though testosterone treatment improves liver injury and metabolic syndrome, and its effect on type two diabetes mellitus is well-documented ( Sun et al, 2021 ), testosterone effects on hepatic injury are still limited. In the present study, we conducted an experimental prospective study on the effect of testosterone treatment on liver injury by assessing liver enzymes, metabolic and oxidative stress, and real-time PCR for the liver and prostate.…”

The role of sex hormones and receptors in HBV infection and development of HBV‐related HCC

“…45,46 In cohort study noticed that hormone level significantly changes HBV-related acute-on-chronic liver failure (HBV-ACLF) and HCC patients. 47,48 Besides, hormone related therapy reduced HCC risk and improved survival outcome in HBV infection female patients. 49,50 Thus, Sex hormone and related receptors play important roles in gender disparity in HBV infection and HCC.…”

“…In vivo studies found that sex hormones regulated HBV replication and transcription, and estrogen supplement suppress chemical‐induced HCC cells proliferation 45,46 . In cohort study noticed that hormone level significantly changes HBV‐related acute‐on‐chronic liver failure (HBV‐ACLF) and HCC patients 47,48 . Besides, hormone related therapy reduced HCC risk and improved survival outcome in HBV infection female patients 49,50 .…”