Abstract
Background
Corticosteroid therapy has been commonly administered to patients with acute liver injury (ALI)/acute liver failure (ALF) in Japan to prevent the development of hepatic encephalopathy, but the appropriate timing to start corticosteroid therapy has not been determined and optimal response evaluation of the therapy has not been conducted. We prospectively investigated the optimal timing to start therapy on the established severity indication: the Japan Hepatic Encephalopathy Prediction Model (JHEPM) and prothrombin time (PT).
Methods
This prospective observational study enrolled 469 patients with ALI/ALF from 2004 to 2015. We evaluated 44 patients with ALF on high-dose corticosteroid therapy before hepatic coma development. The predictive performance for coma development was assessed using the receiver operator curve method in both PT and JHEPM probability the day before administering high-dose corticosteroid therapy.
Results
Among these patients, nine developed hepatic coma after the therapy. Selection bias was adjusted using propensity score method. High-dose corticosteroid therapy tended to decrease the risk of coma development although there was no statistical significance. The cut-off value of 53%, 1.95, and 39% in JHEPM probability, PT-international normalized ratio (PT-INR), and PT activity, respectively, showed high sensitivity and specificity.
Conclusions
We propose the appropriate timing to start high-dose corticosteroid therapy in patients with ALI/ALF; 40% of JHEPM probability, 1.53 of PT-INR, and 52% of PT because these values were theoretically discriminated at 98% coverage to the patients with coma. Because the study contained selection bias, the appropriate timing for therapy should be confirmed in a future prospective study.
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Abbreviations
- ALF:
-
Acute liver failure
- ALI:
-
Acute liver injury
- ALT:
-
Alanine aminotransferase
- AST:
-
Aspartate transaminase
- AUROC:
-
Area under the receiver operating characteristic curve
- JHEPM:
-
Japan Hepatic Encephalopathy Prediction Model
- Cre:
-
Creatinine
- PT:
-
Prothrombin time activity
- PT-INR:
-
Prothrombin time-international normalized ratio
- ROC:
-
Receiver–operator curve
- TBil:
-
Total bilirubin
- WBC:
-
White blood cell counts
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Acknowledgements
We thank Koko Motodate for providing excellent secretarial support. This study was supported in part by Grants-in-Aid from the Ministry of Health, Labor and Welfare of Japan to the Intractable Hepatobiliary Diseases Study Group (JP16K21307 and JP16K09370).
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535_2017_1306_MOESM2_ESM.pptx
Supplementary material 2 (PPTX 240 kb) Supplemental Figure Legend. Serial changes of PT and PT-INR are compared between patients with high-dose corticosteroid therapy (Pulse) and those without the Pulse. A and B: One hundred twenty-one patients were divided into the following two groups: 77 patients without high-dose corticosteroid therapy and 44 patients with the therapy. Serial changes in PT-INR (A) and PT (B) are presented as line charts. Y axis indicates each value. X axis indicates timepoints of each evaluation. Statistical significance was evaluated using the Friedman test, and defined as a p value < 0.05. No significant difference is presented as n.s
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Kakisaka, K., Kataoka, K., Suzuki, Y. et al. Appropriate timing to start and optimal response evaluation of high-dose corticosteroid therapy for patients with acute liver failure. J Gastroenterol 52, 977–985 (2017). https://doi.org/10.1007/s00535-017-1306-5
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DOI: https://doi.org/10.1007/s00535-017-1306-5