HBV‐related acute‐on‐chronic liver failure (HBV‐ACLF) deteriorates rapidly in the short term, which necessitates accurate initial clinical decision making.

To develop a novel prognostic score for patients with HBV‐ACLF and clarify the role of thyroid hormones in HBV‐ACLF.

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.

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.

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.