Acute Liver Injury - Differential Diagnosis Algorithm



Vascular Causes of Acute Liver Injury: 

 • Hepatic vein: Budd-chiari syndrome, Congestion/CHF, Venoocclusive disease

 • Hepatic artery: Shock liver, Thrombosis, Emboli



Hepatocellular Acute Liver Injury:

 • Infectious: HAV, HBV, HCV, HEV, EBV, HSV, CMV, VZV

 • Trauma: Shock liver

 • Metabolic/Hereditary: Wilson Disease, Hemochromatosis, Celiac disease

 • Autoimmune: Autoimmune hepatitis, PBC, PSC, IgG4, HLH

 • Neoplasm - Infiltration: Often breast CA, small cell lung CA, lymphoma, melanoma, myeloma

 • Pregnancy: HELLP

 • Iatrogenic: DILI, Tyelenol, Mushroom poisoning, ETOH



Cholestatic Acute Liver Injury:

 • Extrahepatic - Biliary: Choledocholithiasis, Biliary Stricture, Malignancy, Liver Fluke, Ascariasis, Choledochal cyst

 • Intrahepatic - Obstruction: Biliary stone, Malignancy, PBC, PSC, Cystic fibrosis, Sickle cell, GVHD, Infiltrative



Labs in Hepatocellular Injury:

 • AST: Less specific to liver than ALT

 • ALT: Specific to liver than AST

 • GGT: 

	- Specific to liver

	- Assists in liver specificity to elevated ALP

 • AST/ALT > ALP: Typical of hepatocellular injury

 • Bilirubin - +/- elevation



Labs in Cholestatic Injury:

 • ALP - Surface of bile duct epithelia:

	- Cholestasis/Bile salts augment synthesis of ALP

	- Due to synthesis rises later

	- Half-life: 1 week

 • Direct bilirubin: ↑

 • AST: ↑

 • ALT: ↑

 • GGT/5-NT: ↑

	- ALP > AST/ALT: typical of cholestatic disease

	- If ALP ↑: Check GGT & 5-nucleotidase (5-NT)

	- If both are normal, ALP is from extrahepatic source

	- Tests of synthetic function may be abnormal



AST:ALT Ratios:

 • Alcoholic liver disease: > 2

 • NASH, Chronic viral hepatitis: < 1

 • Cirrhosis: > 1

 • Acute muscle injury: > 3

 • Chronic muscle injury: ~ 1



Unconjugated Bili > 90% of Total Bili Etiology:

 • Gilbert's syndrome

 • Hemolysis



Nonhepatic Source of Liver Enzyme Elevation:

 • Bilirubin: RBC (hemolysis, bleeding, hematoma)

 • AST: Skeletal muscle, cardiac muscle, RBC, kidney, brain

 • ALT: Skeletal muscle, cardiac muscle, kidneys

 • LDH: Heart, RBC (hemolysis)

 • ALP: Bone, first trimester placenta, kidneys, intestines, white blood cells



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