Acute liver failure in adults: Etiology, clinical manifestations, and diagnosis
- Eric Goldberg, MD
Eric Goldberg, MD
- Associate Professor of Medicine
- University of Maryland School of Medicine
- Sanjiv Chopra, MD, MACP
Sanjiv Chopra, MD, MACP
- Editor-in-Chief — Gastroenterology/Hepatology
- Section Editor — General Hepatology
- Section Editor — Gallbladder and Biliary Tract Disease
- Professor of Medicine
- Harvard Medical School
- Senior Consultant in Hepatology
- James Tullis Firm Chief
- Beth Israel Deaconess Medical Center
- Section Editor
- Robert S Brown, Jr, MD, MPH
Robert S Brown, Jr, MD, MPH
- Section Editor — Liver Transplantation
- Vice Chair, Transitions of Care, Department of Medicine
- Interim Chief, Division of Gastroenterology and Hepatology
- Weill Cornell Medical College
- Professor of Clinical Medicine, Columbia University College of Physicians & Surgeons
Acute liver failure is characterized by acute liver injury, hepatic encephalopathy, and an elevated prothrombin time/international normalized ratio (INR). It has also been referred to as fulminant hepatic failure, acute hepatic necrosis, fulminant hepatic necrosis, and fulminant hepatitis. Untreated, the prognosis is poor, so timely recognition and management of patients with acute liver failure is crucial . Whenever possible, patients with acute liver failure should be managed in an intensive care unit at a facility capable of performing liver transplantation.
This topic will review the etiology, clinical manifestations, and diagnosis of acute liver failure in adults. The prognosis and management of patients with acute liver failure is discussed separately. (See "Acute liver failure in adults: Management and prognosis".)
Acute liver failure refers to the development of severe acute liver injury with encephalopathy and impaired synthetic function (INR of ≥1.5) in a patient without cirrhosis or preexisting liver disease [2,3]. While the time course that differentiates acute liver failure from chronic liver failure varies between reports, a commonly used cutoff is an illness duration of <26 weeks.
Acute liver failure may also be diagnosed in patients with previously undiagnosed Wilson disease, vertically acquired hepatitis B virus, or autoimmune hepatitis, in whom underlying cirrhosis may be present, provided the disease has been recognized for <26 weeks. On the other hand, patients with acute severe alcoholic hepatitis, even if recognized for <26 weeks, are considered to have acute-on-chronic liver failure since most have a long history of heavy drinking. The approach to such patients is discussed elsewhere. (See "Clinical manifestations and diagnosis of alcoholic fatty liver disease and alcoholic cirrhosis" and "Prognosis and management of alcoholic fatty liver disease and alcoholic cirrhosis".)
- Lee WM, Squires RH Jr, Nyberg SL, et al. Acute liver failure: Summary of a workshop. Hepatology 2008; 47:1401.
- http://www.aasld.org/practiceguidelines/Documents/AcuteLiverFailureUpdate2011.pdf (Accessed on August 08, 2012).
- Lee WM, Stravitz RT, Larson AM. Introduction to the revised American Association for the Study of Liver Diseases Position Paper on acute liver failure 2011. Hepatology 2012; 55:965.
- Lidofsky SD. Liver transplantation for fulminant hepatic failure. Gastroenterol Clin North Am 1993; 22:257.
- Gill RQ, Sterling RK. Acute liver failure. J Clin Gastroenterol 2001; 33:191.
- Wright G, Wilmore S, Makanyanga J, et al. Liver transplant for adult hemophagocytic lymphohistiocytosis: case report and literature review. Exp Clin Transplant 2012; 10:508.
- Lee WM. Etiologies of acute liver failure. Semin Liver Dis 2008; 28:142.
- O'Grady JG, Portmann B, Williams R. Fulminant hepatic failure. In: Diseases of the Liver, Schiff L, Schiff R (Eds), Lippincott, Philadelphia 1993.
- 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.
- Kemmer NM, Miskovsky EP. Hepatitis A. Infect Dis Clin North Am 2000; 14:605.
- Hoofnagle JH, Carithers RL Jr, Shapiro C, Ascher N. Fulminant hepatic failure: summary of a workshop. Hepatology 1995; 21:240.
- Wright TL, Mamish D, Combs C, et al. Hepatitis B virus and apparent fulminant non-A, non-B hepatitis. Lancet 1992; 339:952.
- Chu CM, Yeh CT, Liaw YF. Fulminant hepatic failure in acute hepatitis C: increased risk in chronic carriers of hepatitis B virus. Gut 1999; 45:613.
- Lee WM. Acute liver failure. N Engl J Med 1993; 329:1862.
- Muñoz SJ. Difficult management problems in fulminant hepatic failure. Semin Liver Dis 1993; 13:395.
- Ellis AJ, Wendon JA, Williams R. Subclinical seizure activity and prophylactic phenytoin infusion in acute liver failure: a controlled clinical trial. Hepatology 2000; 32:536.
- Kaufman B, Gandhi SA, Louie E, et al. Herpes simplex virus hepatitis: case report and review. Clin Infect Dis 1997; 24:334.
- Schiødt FV, Balko J, Schilsky M, et al. Thrombopoietin in acute liver failure. Hepatology 2003; 37:558.
- Stravitz RT, Lisman T, Luketic VA, et al. Minimal effects of acute liver injury/acute liver failure on hemostasis as assessed by thromboelastography. J Hepatol 2012; 56:129.
- Agarwal B, Wright G, Gatt A, et al. Evaluation of coagulation abnormalities in acute liver failure. J Hepatol 2012; 57:780.
- Caraceni P, Van Thiel DH. Acute liver failure. Lancet 1995; 345:163.
- O'Grady JG, Williams R. Acute liver failure. In: Gastrointestinal emergencies, Gilmore IT, Shields R (Eds), WB Saunders, Eastbourne 1992. p.104.
- Tujios SR, Hynan LS, Vazquez MA, et al. Risk factors and outcomes of acute kidney injury in patients with acute liver failure. Clin Gastroenterol Hepatol 2015; 13:352.
- Mas A, Rodés J. Fulminant hepatic failure. Lancet 1997; 349:1081.
- Shakil AO, Jones BC, Lee RG, et al. Prognostic value of abdominal CT scanning and hepatic histopathology in patients with acute liver failure. Dig Dis Sci 2000; 45:334.
- Poff JA, Coakley FV, Qayyum A, et al. Frequency and histopathologic basis of hepatic surface nodularity in patients with fulminant hepatic failure. Radiology 2008; 249:518.
- Chavarria L, Alonso J, Rovira A, Córdoba J. Neuroimaging in acute liver failure. Neurochem Int 2011; 59:1175.
- Amini M, Runyon BA. Alcoholic hepatitis 2010: a clinician's guide to diagnosis and therapy. World J Gastroenterol 2010; 16:4905.
- Mochida S, Takikawa Y, Nakayama N, et al. Diagnostic criteria of acute liver failure: A report by the Intractable Hepato-Biliary Diseases Study Group of Japan. Hepatol Res 2011; 41:805.
- Viral hepatitis
- Acetaminophen and other hepatotoxins
- Idiosyncratic drug reactions
- CLINICAL MANIFESTATIONS
- Physical examination findings
- - Neurologic examination
- - Other physical examination findings
- Laboratory test abnormalities
- - Laboratory findings associated with specific diagnoses
- Imaging and other studies
- Diagnosing acute liver failure
- Determining the cause of acute liver failure
- - Timing of the evaluation
- - History
- - Physical examination
- - Laboratory evaluation
- - Imaging studies
- - Liver biopsy
- DIFFERENTIAL DIAGNOSIS
- SUMMARY AND RECOMMENDATIONS