HINT: a novel prognostic model for patients with hepatitis B virus-related acute-on-chronic liver failure

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.