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.

Condition	Differentiating signs and symtoms	Differentiating Tests
Acute hepatits	Jaundice and coagulopathy may be present. Severe acute hepatitis is followed very closely as it has a potential to develop into acute or subacute hepatic failure. Acute hepatitis would not be considered acute liver failure unless hepatic encephalopathy is present. Common causes are viral hepatitis, acetaminophen overdose, alcoholic hepatitis, autoimmune hepatitis and metabolic disorders such as Wilson's disease and hemochromatosis.	Hepatic encephalopathy is absent. Grades of hepatic encephalopathy are: Grade 1: Trivial lack of awareness; euphoria or anxiety; shortened attention span; impaired performance of addition. 67% of cirrhotic patients may have 'minimal hepatic encephalopathy. 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	Jaundice can be seen due to Intra or extrahepatic biliary obstruction, as well as intrahepatic cholestasis due to conditions like drug-induced liver injury.. The absence of hepatic encephalopathy and coagulopathy will differentiate it from acute liver failure.	Absence of hepatic encephalopathy. Normal PT/INR.
Hemolysis	May have jaundice with increased indirect (unconjugated) serum bilirubin. Liver dysfunction may not be present. So, coagulopathy and hepatic encephalopathy would not be there. Common examples are hemolytic anemias.	Absence of hepatic encephalopathy. Normal PT/INR. Abnormal peripheral blood smear.

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

Disease History and clinical manifestations Diagnosis Lab Findings Other blood tests Other diagnostic AST ALT ALK BLR Indirect BLR Direct Viral serology Type of jaundice Pruritis RUQ pain Fever Family history Common bile duct stone Cholestatic Jaundice + + - -/+ 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 PCR or ELISA Primary biliary cirrhosis + -/+ - -/+ N/↑ N/↑ ↑ N ↑ - AMA positive Liver biopsy Primary sclerosing cholangitis + -/+ - -/+ N/↑ N/↑ ↑ N ↑ - Beading on MRCP Liver biopsy