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Aim: To weight the prognostic value of thyroid hormones in catastrophic acute‐on‐chronic liver failure (ACLF). Methods: A retrospective cohort (n = 635) and two prospective cohorts (n = 353, and 198) were enrolled in this study. The performance of a novel developed prognostic score was assessed from aspects of reliability, discrimination, and clinical net benefit. Results: Thyroid‐stimulating hormone (TSH) was identified to have the most potential as a prognostic predictor for hepatitis B virus‐related ACLF among thyroid hormones. The novel score (modified chronic liver failure–organ failure score [mCLIF‐OFs]) was developed with weighted TSH and other scored organs in the CLIF‐OFs using the retrospective cohort (n = 635). The predicted risk and observed probabilities of death were comparable across the deciles of mCLIF‐OFs (Hosmer–Lemeshow χ2 = 4.28, p = 0.83; Brier scaled = 11.9). The C‐index of mCLIF‐OFs (0.885 [0.883–0.887]) for 30‐day mortality was significantly higher than that of the CLIF‐OFs, chronic liver failure–sequential organ failure assessment score (CLIF‐SOFAs), CLIF‐C ACLFs, Model of End‐stage Liver Disease (MELD), and Child–Pugh (all p < 0.001). The absolute improvements of prediction error rates of the mCLIF‐OFs compared to the above five scores were from 19.0% to 61.1%. After the analysis of probability density function, the mCLIF‐OFs showed the least overlapping coefficients (27.9%) among the above prognostic scores. Additionally, the mCLIF‐OFs showed greater net benefit than the above five prognostic scores over a wide range of risk threshold of death. Similar results were validated in two prospective ACLF cohorts with HBV and non‐HBV etiologies. Conclusion: Weighted TSH portended the outcome of ACLF patients, which could be treated as a "damaged organ" of the hypothalamic–pituitary–thyroid axis. The novel mCLIF‐OFs is a reliable prognostic score with better discrimination power and clinical net benefit than CLIF‐OFs, CLIF‐SOFAs, CLIF‐C ACLFs, MELD, and Child–Pugh. [ABSTRACT FROM AUTHOR]

Aim: To determine the prognostic risk factors of patients with hepatitis B virus related acute‐on‐chronic liver failure (HBV‐ACLF) treated with plasma exchange (PE)‐based artificial liver support system (ALSS), and create a prognostic predictive model. Methods: A total of 304 HBV‐ACLF patients who received PE‐based ALSS were retrospectively analyzed. Potential prognostic factors on admission associated with survival were investigated. Of note, 101 additional patients were analyzed to validate the performance of the prognostic models. Results: According to 28‐day survival, a total of 207 patients who survived and 97 non‐survivors were identified in the derivation group. Overall, 268 (88.2%) ACLF cases were caused by reactivation of HBV. Cox proportional hazards regression model revealed that age, total bilirubin, ln (alpha‐fetoprotein [AFP]), encephalopathy (HE) score, sodium level, and international normalized ratio (INR) were independent risk factors of short‐term prognosis. We built a model named ALSS‐prognosis model (APM) to predict the 28‐day survival of HBV‐ACLF patients with ALSS; the model APM showed potentially better predictive performance for both the derivation and validation groups than MELD, MELD‐Na, and CLIF‐C ACLF score. Conclusions: Low AFP was found to be an independent risk factor for high mortality in HBV‐ACLF patients treated with PE‐based ALSS. We generated a new model containing AFP, namely APM, which showed potentially better prediction performance than MELD, MELD‐Na, and CLIF‐C ACLF score for short‐term outcomes, and could aid physicians in making optimal therapeutic decisions. [ABSTRACT FROM AUTHOR]

Tectorigenin has received attention due to its antiproliferation, anti-inflammatory, and antioxidant activities. In this study, we investigated the effects of tectorigenin on lipopolysaccharide (LPS)/D-galactosamine(D-GalN)-induced fulminant hepatic failure (FHF) in mice and LPS-stimulated macrophages (RAW 264.7 cells). Pretreatment with tectorigenin significantly reduced the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), histological injury, apoptosis, and the mortality of FHF mice, by suppressing the production of inflammatory cytokines such as TNF-α and IL-6. Tectorigenin also suppressed the activation of the inflammatory response in LPS-stimulated RAW 264.7 cells. Tectorigenin-induced protection is mediated through its mitigation of TLR4 expression, inhibition of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathway activation, and promotion of autophagy in FHF mice and LPS-stimulated RAW 264.7 cells. Therefore, tectorigenin has therapeutic potential for FHF in mice via the regulation of TLR4/MAPK and TLR4/NF-κB pathways and autophagy. [ABSTRACT FROM AUTHOR]

Summary: Background: HBV‐related acute‐on‐chronic liver failure (HBV‐ACLF) deteriorates rapidly in the short term, which necessitates accurate initial clinical decision making. Aims: To develop a novel prognostic score for patients with HBV‐ACLF and clarify the role of thyroid hormones in HBV‐ACLF. Methods: A retrospective cohort of 635 HBV‐ACLF patients was enrolled to develop and validate a novel prognostic score for HBV‐ACLF. Additionally, a cross‐sectional cohort (n = 199) and a prospective longitudinal HBV‐ACLF cohort (n = 56) were recruited to clarify the association between thyroid hormone status and the 30‐day mortality of HBV‐ACLF. Results: HINT, a novel prognostic score based on hepatic encephalopathy, INR, neutrophil count, and thyroid‐stimulating hormone (TSH) using the deriving cohort (n = 426), was significantly higher in non‐survivors than survivors (1.17 ± 2.38 vs −1.87 ± 1.26, P < 0.0001). The AUROC of HINT for 30‐day mortality was 0.889, which was significantly higher than that of the Child‐Pugh, MELD, CLIF‐SOFA, CLIF‐C ACLF, and COSSH‐ACLF scores (all P < 0.05). These results were confirmed in the validation cohort (n = 209), except that the AUROC of HINT was comparable to that of COSSH‐ACLF (P = 0.357). Among thyroid hormones, only the TSH level on admission was significantly lower in non‐survivors than in survivors (P = 0.01). During the 14‐day longitudinal observation, TSH levels increased significantly in the improvement group (P < 0.001) but did not change in the deterioration or fluctuation groups, and gradually increased in survivors (P < 0.001) but not in non‐survivors. Conclusions: HINT, as a prognostic score for HBV‐ACLF, is simpler than and superior to the Child‐Pugh, MELD, CLIF‐SOFA, and CLIF‐C ACLF scores and at least comparable with the COSSH‐ACLF score. Sequential TSH measurements may facilitate prediction of the clinical course of ACLF. [ABSTRACT FROM AUTHOR]

Artificial liver support systems (ALSS) are widely used to treat patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). The aims of the present study were to investigate the subgroups of patients with HBV-ACLF who may benefit from ALSS therapy, and the relevant patient-specific factors. 489 ALSS-treated HBV-ACLF patients were enrolled, and served as derivation and validation cohorts for classification and regression tree (CART) analysis. CART analysis identified three factors prognostic of survival: hepatic encephalopathy (HE), prothrombin time (PT), and total bilirubin (TBil) level; and two distinct risk groups: low (28-day mortality 10.2–39.5%) and high risk (63.8–91.1%). The CART model showed that patients lacking HE and with a PT ≤ 27.8 s and a TBil level ≤455 μmol/L experienced less 28-day mortality after ALSS therapy. For HBV-ACLF patients with HE and a PT > 27.8 s, mortality remained high after such therapy. Patients lacking HE with a PT ≤ 27.8 s and TBil level ≤ 455 μmol/L may benefit markedly from ALSS therapy. For HBV-ACLF patients at high risk, unnecessary ALSS therapy should be avoided. The CART model is a novel user-friendly tool for screening HBV-ACLF patient eligibility for ALSS therapy, and will aid clinicians via ACLF risk stratification and therapeutic guidance. [ABSTRACT FROM AUTHOR]