Skip to main content
Top
Published in: Journal of Gastroenterology 8/2017

01-08-2017 | Original Article—Liver, Pancreas, and Biliary Tract

Appropriate timing to start and optimal response evaluation of high-dose corticosteroid therapy for patients with acute liver failure

Authors: Keisuke Kakisaka, Kojiro Kataoka, Yuji Suzuki, Hidekatsu Kuroda, Yasuhiro Takikawa

Published in: Journal of Gastroenterology | Issue 8/2017

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Sugawara K, Nakayama N, Mochida S. Acute liver failure in Japan: definition, classification, and prediction of the outcome. J Gastroenterol. 2012;47:849–61.CrossRefPubMedPubMedCentral Sugawara K, Nakayama N, Mochida S. Acute liver failure in Japan: definition, classification, and prediction of the outcome. J Gastroenterol. 2012;47:849–61.CrossRefPubMedPubMedCentral
2.
go back to reference Oketani M, Ido A, Tsubouchi H. Changing etiologies and outcomes of acute liver failure: a perspective from Japan. J Gastroenterol Hepatol. 2011;26(Suppl 1):65–71.CrossRefPubMed Oketani M, Ido A, Tsubouchi H. Changing etiologies and outcomes of acute liver failure: a perspective from Japan. J Gastroenterol Hepatol. 2011;26(Suppl 1):65–71.CrossRefPubMed
3.
go back to reference Yamashiki N, Sugawara Y, Tamura S, et al. Outcomes after living donor liver transplantation for acute liver failure in Japan: results of a nationwide survey. Liver Transpl. 2012;18:1069–77.CrossRefPubMed Yamashiki N, Sugawara Y, Tamura S, et al. Outcomes after living donor liver transplantation for acute liver failure in Japan: results of a nationwide survey. Liver Transpl. 2012;18:1069–77.CrossRefPubMed
4.
go back to reference Ware AJ, Jones RE, Shorey JW, et al. A controlled trial of steroid therapy in massive hepatic necrosis. Am J Gastroenterol. 1974;62:130–3.PubMed Ware AJ, Jones RE, Shorey JW, et al. A controlled trial of steroid therapy in massive hepatic necrosis. Am J Gastroenterol. 1974;62:130–3.PubMed
5.
go back to reference Gregory PB, Knauer CM, Kempson RL, et al. Steroid therapy in severe viral hepatitis. A double-blind, randomized trial of methyl-prednisolone versus placebo. N Engl J Med. 1976;294:681–7.CrossRefPubMed Gregory PB, Knauer CM, Kempson RL, et al. Steroid therapy in severe viral hepatitis. A double-blind, randomized trial of methyl-prednisolone versus placebo. N Engl J Med. 1976;294:681–7.CrossRefPubMed
6.
go back to reference Redeker AG, Schweitzer IL, Yamahiro HS. Letter: Randomization of corticosteroid therapy in fulminant hepatitis. N Engl J Med. 1976;294:728–9.CrossRefPubMed Redeker AG, Schweitzer IL, Yamahiro HS. Letter: Randomization of corticosteroid therapy in fulminant hepatitis. N Engl J Med. 1976;294:728–9.CrossRefPubMed
7.
go back to reference Fujiwara K, Yasui S, Yonemitsu Y, et al. Efficacy of high-dose corticosteroid in the early stage of viral acute liver failure. Hepatol Res. 2014;44:491–501.CrossRefPubMed Fujiwara K, Yasui S, Yonemitsu Y, et al. Efficacy of high-dose corticosteroid in the early stage of viral acute liver failure. Hepatol Res. 2014;44:491–501.CrossRefPubMed
8.
go back to reference Ohira H, Takahashi A. Current trends in the diagnosis and treatment of autoimmune hepatitis in Japan. Hepatol Res. 2012;42:131–8.CrossRefPubMed Ohira H, Takahashi A. Current trends in the diagnosis and treatment of autoimmune hepatitis in Japan. Hepatol Res. 2012;42:131–8.CrossRefPubMed
9.
go back to reference Kakisaka K, Kataoka K, Suzuki Y, et al. Necrotic cell death and suppression of T-cell immunity characterized acute liver failure due to drug-induced liver injury. Cytokine. 2016;86:21–8.CrossRefPubMed Kakisaka K, Kataoka K, Suzuki Y, et al. Necrotic cell death and suppression of T-cell immunity characterized acute liver failure due to drug-induced liver injury. Cytokine. 2016;86:21–8.CrossRefPubMed
10.
go back to reference Yasui S, Fujiwara K, Yonemitsu Y, et al. Clinicopathological features of severe and fulminant forms of autoimmune hepatitis. J Gastroenterol. 2011;46:378–90.CrossRefPubMed Yasui S, Fujiwara K, Yonemitsu Y, et al. Clinicopathological features of severe and fulminant forms of autoimmune hepatitis. J Gastroenterol. 2011;46:378–90.CrossRefPubMed
11.
go back to reference Coutinho AE, Chapman KE. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol. 2011;335:2–13.CrossRefPubMedPubMedCentral Coutinho AE, Chapman KE. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol. 2011;335:2–13.CrossRefPubMedPubMedCentral
12.
go back to reference Karkhanis J, Verna EC, Chang MS, et al. Steroid use in acute liver failure. Hepatology. 2014;59:612–21.CrossRefPubMed Karkhanis J, Verna EC, Chang MS, et al. Steroid use in acute liver failure. Hepatology. 2014;59:612–21.CrossRefPubMed
13.
go back to reference Takikawa Y, Endo R, Suzuki K, et al. Early prediction of short-term development of hepatic encephalopathy in patients with acute liver disease unrelated to paracetamol. A prospective study in Japan. J Hepatol. 2009;51:1021–9.CrossRefPubMed Takikawa Y, Endo R, Suzuki K, et al. Early prediction of short-term development of hepatic encephalopathy in patients with acute liver disease unrelated to paracetamol. A prospective study in Japan. J Hepatol. 2009;51:1021–9.CrossRefPubMed
14.
go back to reference Kakisaka K, Kataoka K, Onodera M, et al. Alpha-fetoprotein: a biomarker for the recruitment of progenitor cells in the liver in patients with acute liver injury or failure. Hepatol Res. 2014;45:E12–20.CrossRefPubMed Kakisaka K, Kataoka K, Onodera M, et al. Alpha-fetoprotein: a biomarker for the recruitment of progenitor cells in the liver in patients with acute liver injury or failure. Hepatol Res. 2014;45:E12–20.CrossRefPubMed
15.
go back to reference Kakisaka K, Kataoka K, Kuroda H, et al. Predictive formula for acute liver failure is useful for predicting the prognosis of patients with acute-on-chronic liver failure. Hepatol Res. 2016;46:459–67.CrossRefPubMed Kakisaka K, Kataoka K, Kuroda H, et al. Predictive formula for acute liver failure is useful for predicting the prognosis of patients with acute-on-chronic liver failure. Hepatol Res. 2016;46:459–67.CrossRefPubMed
16.
go back to reference Oketani M, Ido A, Nakayama N, et al. Etiology and prognosis of fulminant hepatitis and late-onset hepatic failure in Japan: summary of the annual nationwide survey between 2004 and 2009. Hepatol Res. 2013;43:97–105.CrossRefPubMed Oketani M, Ido A, Nakayama N, et al. Etiology and prognosis of fulminant hepatitis and late-onset hepatic failure in Japan: summary of the annual nationwide survey between 2004 and 2009. Hepatol Res. 2013;43:97–105.CrossRefPubMed
17.
go back to reference Randomised trial of steroid therapy in acute liver failure. Report from the European Association for the Study of the Liver (EASL). Gut. 1979;20:620–623. Randomised trial of steroid therapy in acute liver failure. Report from the European Association for the Study of the Liver (EASL). Gut. 1979;20:620–623.
19.
go back to reference Takikawa Y, Harada M, Wang T, et al. Usefulness and accuracy of the international normalized ratio and activity percent of prothrombin time in patients with liver disease. Hepatol Res. 2014;44:92–101.CrossRefPubMed Takikawa Y, Harada M, Wang T, et al. Usefulness and accuracy of the international normalized ratio and activity percent of prothrombin time in patients with liver disease. Hepatol Res. 2014;44:92–101.CrossRefPubMed
20.
go back to reference Kudo M, Todo A, Ikekubo K, et al. Quantitative assessment of hepatocellular function through in vivo radioreceptor imaging with technetium 99m galactosyl human serum albumin. Hepatology. 1993;17:814–9.PubMed Kudo M, Todo A, Ikekubo K, et al. Quantitative assessment of hepatocellular function through in vivo radioreceptor imaging with technetium 99m galactosyl human serum albumin. Hepatology. 1993;17:814–9.PubMed
21.
go back to reference Kakisaka K, Kuroda H, Abe T, et al. Hepatic hemodynamics and elevation of liver stiffness as possible predictive markers of late-onset hepatic failure. Intern Med. 2016;55:1091–5.CrossRefPubMed Kakisaka K, Kuroda H, Abe T, et al. Hepatic hemodynamics and elevation of liver stiffness as possible predictive markers of late-onset hepatic failure. Intern Med. 2016;55:1091–5.CrossRefPubMed
Metadata
Title
Appropriate timing to start and optimal response evaluation of high-dose corticosteroid therapy for patients with acute liver failure
Authors
Keisuke Kakisaka
Kojiro Kataoka
Yuji Suzuki
Hidekatsu Kuroda
Yasuhiro Takikawa
Publication date
01-08-2017
Publisher
Springer Japan
Published in
Journal of Gastroenterology / Issue 8/2017
Print ISSN: 0944-1174
Electronic ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-017-1306-5

Other articles of this Issue 8/2017

Journal of Gastroenterology 8/2017 Go to the issue

Original Article—Liver, Pancreas, and Biliary Tract

Nationwide epidemiological survey of early chronic pancreatitis in Japan