Weighted thyroid‐stimulating hormone disturbance in prognosis of hepatitis B virus‐related acute‐on‐chronic liver failure

Abstract

AbstractAimTo weight the prognostic value of thyroid hormones in catastrophic acute‐on‐chronic liver failure (ACLF).MethodsA 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.ResultsThyroid‐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.ConclusionWeighted 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.