The Natural History of Severe Acute Liver Injury.

• Type of Material: Article
• Authors: David G. Koch, Medical University of South Carolina; J.L. Speiser, Medical University of South Carolina; V. Durkalski, Medical University of South Carolina; R.J. Fontana, University of Michigan; T. Davern, California Pacific Medical Center; B. McGuire, University of Alabama; R.T. Stravitz, Virginia Commonwealth University; A.M. Larson, University of Washington; I. Liou, University of Washington; O. Fix, Swedish Medical Center Seattle; M.L. Schilsky, Yale University; T. McCashland, University of Nebraska Medical Center; J.E. Hay, Mayo Clinic, Rochester, MN; N. Murray, Baylor University Medical Center; O.S. Shaikh, University of Pittsburgh; D. Ganger, Northwestern University; A. Zaman, Oregon Health Sciences Center; S.B. Han, University of California, Los Angeles; R.T. Chung, Massachusetts General Hospital; R.S. Brown, Albert Einstein Medical Center; S. Munoz, Jr., University of Pennsylvania; K.R. Reddy, University of Pennsylvania; L. Rossaro, University of California, Davis; R. Satyanarayana, Mayo Clinic, Jacksonville, FL; A.J. Hanje, The Ohio State University; J. Olson, University of Kansas Medical Center; Ram Subramanian, Emory University; C. Karvellas, University of Alberta; B. Hameed, University of California, San Francisco; A.H. Sherker, National Institute of Diabetes and Digestive and Kidney Diseases; W.M. Lee, University of Texas Southwestern Medical Center; A. Reuben, Medical University of South Carolina
• Language: English
• Date: 2017-04-25
• Publisher: Nature Publishing Group: Open Access Hybrid Model Option A
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 by the American College of Gastroenterology
• Final Published Version (URL): http://dx.doi.org/10.1038/ajg.2017.98
• Title of Journal or Parent Work: American Journal of Gastroenterology
• ISSN: 0002-9270
• Volume: 112
• Issue: 9
• Start Page: 1389
• End Page: 1396
• Grant/Funding Information: This project was supported by NIDDK U01-DK-58369 over the past 17 years.
• Research Categories: Health Sciences, General; Health Sciences, Medicine and Surgery

Abstract

OBJECTIVES: Acute liver failure (ALF) is classically defined by coagulopathy and hepatic encephalopathy (HE); however, acute liver injury (ALI), i.e., severe acute hepatocyte necrosis without HE, has not been carefully defined nor studied. Our aim is to describe the clinical course of specifically defined ALI, including the risk and clinical predictors of poor outcomes, namely progression to ALF, the need for liver transplantation (LT) and death. METHODS: 386 subjects prospectively enrolled in the Acute Liver Failure Study Group registry between 1 September 2008 through 25 October 2013, met criteria for ALI: International Normalized Ratio (INR)≥2.0 and alanine aminotransferase (ALT)≥10 × elevated (irrespective of bilirubin level) for acetaminophen (N-acetyl-p-aminophenol, APAP) ALI, or INR≥2.0, ALT≥10x elevated, and bilirubin≥3.0 mg/dl for non-APAP ALI, both groups without any discernible HE. Subjects who progressed to poor outcomes (ALF, death, LT) were compared, by univariate analysis, with those who recovered. A model to predict poor outcome was developed using the random forest (RF) procedure. RESULTS: Progression to a poor outcome occurred in 90/386 (23%), primarily in non-APAP (71/179, 40%) vs. only 14/194 (7.2%) in APAP patients comprising 52% of all cases (13 cases did not have an etiology assigned; 5 of whom had a poor outcome). Of 82 variables entered into the RF procedure: etiology, bilirubin, INR, APAP level and duration of jaundice were the most predictive of progression to ALF, LT, or death. CONCLUSIONS: A majority of ALI cases are due to APAP, 93% of whom will improve rapidly and fully recover, while non-APAP patients have a far greater risk of poor outcome and should be targeted for early referral to a liver transplant center.Am J Gastroenterol advance online publication, 25 April 2017; doi:10.1038/ajg.2017.98.