Acute liver failure differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Husnain Shaukat, M.D [2]

Overview

Acute liver failure must be differentiated from other diseases that cause signs and symptoms of jaundice, coagulopathy, and encephalopathy. The differentials include acute hepatitis, cholestatic jaundice, and hemolytic jaundice. The common causes of acute hepatitis causing acute liver failure include acetaminophen toxicity, viral hepatitis, alcoholic hepatitis, autoimmune hepatitis, acute fatty liver of pregnancy, Wilson's disease, ischemic hepatitis and hepatic congestion due to right heart failure and Budd–chiari syndrome.

Differentiating Acute Liver Failure from other Diseases

Acute liver failure must be differentiated from other diseases that cause signs and symptoms of jaundice, coagulopathy, and encephalopathy.[1][2][3][4]

Condition Differentiating signs and symtoms Differentiating Tests
Acute hepatits
  • Severe acute hepatitis is followed very closely as it has a potential to develop into acute or subacute hepatic failure.
  • Hepatic encephalopathy is absent.
  • Grades of hepatic encephalopathy are:
    • Grade 1: Trivial lack of awareness; euphoria or anxiety; shortened attention span.
    • Grade 2: Lethargy or apathy; minimal disorientation for time or place; subtle personality change; inappropriate behavior; impaired performance of subtraction.
    • Grade 3:  Somnolence to semi-stupor, but responsive to verbal stimuli; confusion; gross disorientation.
    • Grade 4:  Coma (unresponsive to verbal or noxious stimuli).
Cholestasis
Hemolysis

Abbreviations: RUQ= Right upper quadrant of the abdomen, LFT= Liver function test, SIRS= Systemic inflammatory response syndrome, ERCP= Endoscopic retrograde cholangiopancreatography, N= Normal, AMA= Anti mitochondrial antibodies, LDH= Lactate dehydrogenase, GI= Gastrointestinal, CT= Computed tomography

Classification of jaundice based on etiology Disease History and clinical manifestations Diagnosis
Lab Findings Other blood tests Other diagnostic
Family history Fever RUQ Pain Pruritis AST ALT ALK BLR Indirect BLR Direct Viral serology
Jaundice Hepatocellular Jaundice Hemochromatosis + - -/+ - ↑/N ↑/N N - Ferritin ↑ Liver biopsy
Wilson's disease + - -/+ - N ↑/N N - Serum cerulloplasmin ↑ Liver biopsy
Viral hepatitis - -/+ - - ↑↑ N ↑/N N + Specific viral antibody for each type -
Alcoholic hepatitis - - - - ↑↑ N ↑/N N - - -
Drug induced hepatitis - -/+ - - N ↑/N N - - -
Autoimmune hepatitis -/+ - - -/+ N ↑/N N - Anti-LKM antibody Liver biopsy
Cholestatic Jaundice Common bile duct stone -/+ - + + N N N - Dilated ducts on sono CT/ERCP
Hepatitis A cholestatic type - -/+ + + N N N + HAV- AB Abdominal ultrasound
EBV / CMV hepatitis - -/+ + + N N N + Positive serology
Primary biliary cirrhosis -/+ - -/+ + N/↑ N/↑ ↑? - AMA positive Liver biopsy
Primary sclerosing cholangitis -/+ - -/+ + N/↑ N/↑ ↑? - Beading on MRCP Liver biopsy
Isolated Jaundice Crigler-Najjar type 2 + - - - N N N N - Genetic testing
Gilbert + - - - N N N N - Genetic testing
Rotor syndrome + - - - N N N N - Genetic testing Liver biopsy
Dubin-Johnson syndrome + - - - N N N N - Genetic testing Liver biopsy
Hereditory spherocytosis + - -/+ - N N N N - Genetic testing Osmotic fragility
G6PD deficiency + - - - N N N N - Genetic testing
Thalassemia + - - - N N N N - Genetic testing
Sickle cell disease + - - - N N N N - Genetic testing
Paroxismal nocturnal hemoglobinoria - - - - N N N N - Flocytometery
Immune hemolysis - -/+ - - N N N N - Autoantibodies
Hematoma - -/+ - - N N N N - Anemia Truma or surgery in history

References

  1. Escorsell A, Mas A, de la Mata M, Spanish Group for the Study of Acute Liver Failure (2007). "Acute liver failure in Spain: analysis of 267 cases". Liver Transpl. 13 (10): 1389–95. doi:10.1002/lt.21119. PMID 17370334.
  2. Bower WA, Johns M, Margolis HS, Williams IT, Bell BP (2007). "Population-based surveillance for acute liver failure". Am J Gastroenterol. 102 (11): 2459–63. doi:10.1111/j.1572-0241.2007.01388.x. PMID 17608778.
  3. Kumar R, Shalimar. Bhatia V, Khanal S, Sreenivas V, Gupta SD; et al. (2010). "Antituberculosis therapy-induced acute liver failure: magnitude, profile, prognosis, and predictors of outcome". Hepatology. 51 (5): 1665–74. doi:10.1002/hep.23534. PMID 20196116.
  4. Lee WM, Stravitz RT, Larson AM (2012). "Introduction to the revised American Association for the Study of Liver Diseases Position Paper on acute liver failure 2011". Hepatology. 55 (3): 965–7. doi:10.1002/hep.25551. PMC 3378702. PMID 22213561.

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