The Natural History of Severe Acute Liver Injury
Open accessAbstract
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.
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Paracetamol accounted for a weighted mean of 55.7% (range 50.0-77.8%) of severe acute liver injury (ALI) and/or ALF.
“Overall, paracetamol accounted for a weighted mean of 55.7% (range 50.0-77.8%) of severe acute liver injury (ALI) and/or ALF [201-208] and 7.3% (range 1.2-29.2%) of drug-induced liver injury (DILI) [209-219] (see Figure 7).”
From Paracetamol (acetaminophen) overdose and hepatotoxicity: mechanism, treatment, prevention measures, and estimates of burden of disease (2023) · cites this paper as [207]
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Cites
Breiman, L. (2001) · Machine Learning · doi:10.1023/a:1010933404324 · Cited by 133,538 · see citing works
Random forests for classification in ecology
Cutler, D. R., Edwards, T. C., Beard, K. H., Cutler, A., Hess, K. T., Gibson, J., & Lawler, J. J. (2007) · Ecology · doi:10.1890/07-0539.1 · Cited by 4,950 · see citing works
Ostapowicz, G., Fontana, R. J., Schiødt, F. V., Larson, A., Davern, T. J., Han, S. H. B., McCashland, T. M., Shakil, A. O., Hay, J. E., Hynan, L., et al. (2002) · Annals of Internal Medicine · doi:10.7326/0003-4819-137-12-200212170-00007 · Cited by 2,227 · see citing works
Self-citationFerenci, P., Lockwood, A. H., Mullen, K. D., Tarter, R. E., Weißenborn, K., & Blei, A. T. (2002) · Hepatology · doi:10.1053/jhep.2002.31250 · Cited by 2,035 · see citing works
Lee, W. M., Squires, R. H., Nyberg, S. L., Doo, E. C., & Hoofnagle, J. H. (2008) · Hepatology · doi:10.1002/hep.22177 · Cited by 769 · see citing works
Self-citationSegal, J. B., & Dzik, S. (2005) · Transfusion · doi:10.1111/j.1537-2995.2005.00546.x · Cited by 662 · see citing works
Surveillance for acute viral hepatitis--United States, 2006.
Wasley, A., Grytdal, S., & Gallagher, K. (2008) · PubMed · Cited by 543 · see citing works
Lessons from look-back in acute liver failure? A single centre experience of 3300 patients
Bernal, W. E., Hyyrylainen, A., Gera, A., Audimoolam, V. K., McPhail, M. J. W., Auzinger, G. M., Rela, M., Heaton, N. D., O’Grady, J. G., Wendon, J. A., et al. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.02.010 · Cited by 435 · see citing works
Surveillance for acute viral hepatitis--United States, 2005.
Wasley, A., Miller, J. T., & Finelli, L. (2007) · PubMed · Cited by 391 · see citing works
Bleeding after liver biopsy does not correlate with indices of peripheral coagulation
Ewe, K. (1981) · Digestive Diseases and Sciences · doi:10.1007/bf01313579 · Cited by 359 · see citing works
Stravitz, R. T., Lisman, T., Luketic, V. A., Sterling, R. K., Puri, P., Fuchs, M. A., Ibrahim, A. E. K., Lee, W. M., & Sanyal, A. J. (2011) · Journal of Hepatology · doi:10.1016/j.jhep.2011.04.020 · Cited by 268 · see citing works
Self-citationFontana, R. J., Hayashi, P. H., Gu, J., Reddy, K. R., Barnhart, H. X., Watkins, P. B., Serrano, J., Lee, W. M., Chalasani, N., Stolz, A., et al. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.03.045 · Cited by 245 · see citing works
Self-citationThe management of fulminant hepatic failure.
Trey, C., & Davidson, C. S. (1970) · PubMed · Cited by 244 · see citing works
Ichaı̈, P., Duclos‐Vallée, J., Guettier, C., Hamida, S. B., Antonini, T., Delvart, V., Saliba, F., Azoulay, D., Castaing, D., & Samuel, D. (2007) · Liver Transplantation · doi:10.1002/lt.21036 · Cited by 242 · see citing works
Surveillance for acute viral hepatitis - United States, 2007.
Daniels, D. S., Grytdal, S., & Wasley, A. (2009) · PubMed · Cited by 221 · see citing works
Hemostasis and Fibrinolysis in Severe Liver Failure and Their Relation to Hemorrhage
Boks, A. L., Brommer, E. J. P., Schalm, S. W., et al. (1986) · Hepatology · doi:10.1002/hep.1840060115 · Cited by 192 · see citing works
Hugenholtz, G. C. G., Adelmeijer, J., Meijers, J. C. M., Porte, R. J., Stravitz, R. T., & Lisman, T. (2013) · Hepatology · doi:10.1002/hep.26372 · Cited by 190 · see citing works
Self-citationEvaluation of coagulation abnormalities in acute liver failure
Agarwal, B., Wright, G. A. K., Gatt, A., et al. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2012.06.020 · Cited by 185 · see citing works
Management of Fulminant Hepatic Failure
Detry, O., Honoré, P., Meurisse, M., & Jacquet, N. J. (1998) · Acta chirurgica Belgica · doi:10.1080/00015458.1998.12098423 · Cited by 161 · see citing works
Yeoman, A. D., Westbrook, R., Zen, Y., Bernal, W. E., Al–Chalabi, T., Wendon, J. A., O’Grady, J. G., & Heneghan, M. A. (2014) · Journal of Hepatology · doi:10.1016/j.jhep.2014.05.021 · Cited by 158 · see citing works
Unrecognized acetaminophen toxicity as a cause of indeterminate acute liver failure
Khandelwal, N., James, L. P., Sanders, C. M., Larson, A. M., Lee, W. M., & and the Acute Liver Failure Study Group (2010) · Hepatology · doi:10.1002/hep.24060 · Cited by 155 · see citing works
Self-citationLisman, T., Bakhtiari, K., Adelmeijer, J., Meijers, J. C. M., Porte, R. J., & Stravitz, R. T. (2012) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2012.04770.x · Cited by 124 · see citing works
Self-citationDevarbhavi, H. C., Singh, R., Patil, M., et al. (2012) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2012.07279.x · Cited by 101 · see citing works
Clinical Features, Diagnosis, and Natural History of Drug-Induced Liver Injury
Fontana, R. J., & Hayashi, P. H. (2014) · Seminars in Liver Disease · doi:10.1055/s-0034-1375955 · Cited by 76 · see citing works
Self-citationRandom forest classification of etiologies for an orphan disease
Speiser, J. L., Durkalski, V., & Lee, W. M. (2014) · Statistics in Medicine · doi:10.1002/sim.6351 · Cited by 59 · see citing works
Self-citationElinav, E., Ben‐Dov, I. Z., Hy‐Am, E., Ackerman, Z., & Ofran, Y. (2004) · Journal of Hepatology · doi:10.1016/j.jhep.2004.09.009 · Cited by 44 · see citing works
Weerasinghe, S. V. W., Moons, D. S., Altshuler, P. J., et al. (2011) · Hepatology · doi:10.1002/hep.24203 · Cited by 31 · see citing works
Acute Hepatitis in Israeli Travelers
Lachish, T., Tandlich, M., & Schwartz, E. (2013) · Journal of Travel Medicine · doi:10.1111/jtm.12039 · Cited by 20 · see citing works
Attempting to predict the unpredictable in acute liver injury
O’Grady, J. (2004) · Journal of Hepatology · doi:10.1016/j.jhep.2004.11.007 · Cited by 17 · see citing works
Slow but Steady Progress in a Field with Many Knowledge Gaps
Hayashi, P. H., & Chalasani, N. (2014) · Seminars in Liver Disease · doi:10.1055/s-0034-1375952 · Cited by 17 · see citing works
Acute liver failure: What is it?
Wlodzimirow, K. A., Eslami, S., Abu–Hanna, A., et al. (2011) · Hepatology · doi:10.1002/hep.25519 · Cited by 4 · see citing works
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Chidiac, A. S., Buckley, N. A., Noghrehchi, F., & Cairns, R. (2023) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2023.2223959 · Cited by 215 · see citing works
Stravitz, R. T., Fontana, R. J., Meinzer, C., Durkalski‐Mauldin, V., Hanje, A. J., Olson, J., Koch, D., Hamid, B., Schilsky, M. L., McGuire, B., et al. (2021) · Hepatology · doi:10.1002/hep.31767 · Cited by 50 · see citing works
Self-citationRole of Hepatitis E Virus Infection in North American Patients With Severe Acute Liver Injury
Fontana, R. J., Engle, R. E., Gottfried, M., Hammed, B., Hanje, J., Durkalski, V., Kleiner, D. E., Nguyen, H., Nishimura, N., Lee, W. M., et al. (2020) · Clinical and Translational Gastroenterology · doi:10.14309/ctg.0000000000000273 · Cited by 9 · see citing works
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- Authors
- Koch, D. G., Speiser, J. L., Durkalski, V, Fontana, R. J., Davern, T., McGuire, B., Stravitz, R. T., Larson, A. M., Liou, I., Fix, O., Schilsky, M. L., McCashland, T., Hay, J. E., Murray, N., Shaikh, O. S., Ganger, D., Zaman, A., Han, S. B., Chung, R. T., Brown, R. S., Munoz, S., Reddy, K. R., Rossaro, L., Satyanarayana, R., Hanje, A. J., Olson, J., Subramanian, R. M., Karvellas, C., Hameed, B., Sherker, A. H., Lee, W. M., & Reuben, A.
- Affiliations
- Medical University of South Carolina (US)
- University of Michigan (US)
- California Pacific Medical Center (US)
- University of Alabama at Birmingham (US)
- Virginia Commonwealth University (US)
- University of Washington (US)
- Swedish Medical Center (US)
- Yale University (US)
- University of Nebraska Medical Center (US)
- Mayo Clinic (US)
- Baylor University Medical Center (US)
- University of Pittsburgh (US)
- Northwestern University (US)
- Oregon Health & Science University (US)
- University of California, Los Angeles (US)
- Massachusetts General Hospital (US)
- Jefferson Einstein Philadelphia Hospital (US)
- University of Pennsylvania (US)
- University of California, Davis (US)
- The Ohio State University (US)
- University of Kansas Medical Center (US)
- Emory University (US)
- University of Alberta (CA)
- University of California, San Francisco (US)
- National Institute of Diabetes and Digestive and Kidney Diseases (US)
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Koch, David G
- ORCID
- Venue
- American Journal of Gastroenterology
- Published
- 2017-09
- Volume
- 112
- Issue
- 9
- Pages
- 1389-1396
- ISSN
- 0002-9270 (ISSN-L)
- PMC
- PMC5587371
- OpenAlex
- W2607713342
- Cited by
- 143
- References
- 31
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 21 · 2023: 13 · 2022: 19 · 2021: 15 · 2020: 20 · 2019: 17 · 2018: 10 · 2017: 6
- FWCI
- 8.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The American Journal of Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK058369, U01DK058369, P30DK043351)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Keywords
- acute liver injury, acute liver failure, acetaminophen hepatotoxicity, liver necrosis, hepatic encephalopathy, liver transplantation, mortality, outcome prediction, random forest, bilirubin, international normalized ratio, natural history (disease)
- MeSH terms
- Adult, Alanine Transaminase, Data Interpretation, Statistical, Female, Hepatic Encephalopathy, Humans, Male, Middle Aged, Prognosis, Registries, Severity of Illness Index, United States, Adverse Drug Reaction Reporting Systems, International Normalized Ratio, Chemical and Drug Induced Liver Injury
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