The Natural History of Severe Acute Liver Injury

David G. Koch, J. L. Speiser, V. Durkalski, R. J. Fontana, T. Davern, B. McGuire, R. T. Stravitz, A. M. Larson, I. Liou, O. Fix, M. L. Schilsky, Timothy M McCashland, J. E. Hay, N. Murray, O. S. Shaikh, D. Ganger, A. Zaman, S. B. Han, R. T. Chung, R. S. Brown & 12 others S. Munoz, K. R. Reddy, L. Rossaro, R. Satyanarayana, A. J. Hanje, J. Olson, R. M. Subramanian, C. Karvellas, B. Hameed, A. H. Sherker, W. M. Lee, A. Reuben

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1389-1396
Number of pages8
JournalAmerican Journal of Gastroenterology
Volume112
Issue number9
DOIs
StatePublished - Sep 1 2017

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Natural History
Acute Liver Failure
Acetaminophen
Liver
Wounds and Injuries
Hepatic Encephalopathy
Liver Transplantation
International Normalized Ratio
Bilirubin
Jaundice
Alanine Transaminase
Registries
Hepatocytes
Necrosis
Referral and Consultation
Transplants
4-aminophenol

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Koch, D. G., Speiser, J. L., Durkalski, V., Fontana, R. J., Davern, T., McGuire, B., ... Reuben, A. (2017). The Natural History of Severe Acute Liver Injury. American Journal of Gastroenterology, 112(9), 1389-1396. https://doi.org/10.1038/ajg.2017.98

The Natural History of Severe Acute Liver Injury. / Koch, David 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, Timothy M; 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.

In: American Journal of Gastroenterology, Vol. 112, No. 9, 01.09.2017, p. 1389-1396.

Research output: Contribution to journalArticle

Koch, DG, Speiser, JL, Durkalski, V, Fontana, RJ, Davern, T, McGuire, B, Stravitz, RT, Larson, AM, Liou, I, Fix, O, Schilsky, ML, McCashland, TM, Hay, JE, Murray, N, Shaikh, OS, Ganger, D, Zaman, A, Han, SB, Chung, RT, Brown, RS, Munoz, S, Reddy, KR, Rossaro, L, Satyanarayana, R, Hanje, AJ, Olson, J, Subramanian, RM, Karvellas, C, Hameed, B, Sherker, AH, Lee, WM & Reuben, A 2017, 'The Natural History of Severe Acute Liver Injury', American Journal of Gastroenterology, vol. 112, no. 9, pp. 1389-1396. https://doi.org/10.1038/ajg.2017.98
Koch DG, Speiser JL, Durkalski V, Fontana RJ, Davern T, McGuire B et al. The Natural History of Severe Acute Liver Injury. American Journal of Gastroenterology. 2017 Sep 1;112(9):1389-1396. https://doi.org/10.1038/ajg.2017.98
Koch, David 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, Timothy M ; 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. / The Natural History of Severe Acute Liver Injury. In: American Journal of Gastroenterology. 2017 ; Vol. 112, No. 9. pp. 1389-1396.
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title = "The Natural History of Severe Acute Liver Injury",
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.",
author = "Koch, {David G.} and Speiser, {J. L.} and V. Durkalski and Fontana, {R. J.} and T. Davern and B. McGuire and Stravitz, {R. T.} and Larson, {A. M.} and I. Liou and O. Fix and Schilsky, {M. L.} and McCashland, {Timothy M} and Hay, {J. E.} and N. Murray and Shaikh, {O. S.} and D. Ganger and A. Zaman and Han, {S. B.} and Chung, {R. T.} and Brown, {R. S.} and S. Munoz and Reddy, {K. R.} and L. Rossaro and R. Satyanarayana and Hanje, {A. J.} and J. Olson and Subramanian, {R. M.} and C. Karvellas and B. Hameed and Sherker, {A. H.} and Lee, {W. M.} and A. Reuben",
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T1 - The Natural History of Severe Acute Liver Injury

AU - Koch, David G.

AU - Speiser, J. L.

AU - Durkalski, V.

AU - Fontana, R. J.

AU - Davern, T.

AU - McGuire, B.

AU - Stravitz, R. T.

AU - Larson, A. M.

AU - Liou, I.

AU - Fix, O.

AU - Schilsky, M. L.

AU - McCashland, Timothy M

AU - Hay, J. E.

AU - Murray, N.

AU - Shaikh, O. S.

AU - Ganger, D.

AU - Zaman, A.

AU - Han, S. B.

AU - Chung, R. T.

AU - Brown, R. S.

AU - Munoz, S.

AU - Reddy, K. R.

AU - Rossaro, L.

AU - Satyanarayana, R.

AU - Hanje, A. J.

AU - Olson, J.

AU - Subramanian, R. M.

AU - Karvellas, C.

AU - Hameed, B.

AU - Sherker, A. H.

AU - Lee, W. M.

AU - Reuben, A.

PY - 2017/9/1

Y1 - 2017/9/1

N2 - 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.

AB - 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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