Transaminitis - Elevated Liver Chemistry Tests
Patterns ...

Transaminitis - Elevated Liver Chemistry Tests

Patterns of Liver Chemistry Test Elevation:

1. Hepatocellular: ALT and AST ↑

2. Cholestatic: ALK-P↑ + direct hyperbilirubinemia

3. Infiltrative: (e.g. malignancy, sarcoid): ALK-P ↑ w/o significant bilis

4. Non-hepatic: e.g. indirect hyperbili, non-hepatic alk phos ↑, non-hepatic AST ↑

Calculate the “R ratio”:

 • R ratio = (ALT/ULN) ÷ (Alk Phos/ULN)

 • Hepatocellular: R ratio > 5

 • Cholestasis: R ratio < 2

 • Mixed: R ratio between 2-5

1. Causes of hepatocellular injury (↑AST/ALT; R ratio >5):

Any degree of AST/ALT elevation:

 • Meds/toxins, e.g. acetaminophen. See list below*

 • ETOH (typically 2:1 AST:ALT ratio, AST<8x ULN)

 • Nonalcoholic fatty liver (often AST & ALT <4x ULN)

 • Viral infection (Hep A-E, CMV, EBV, VZV, HSV)

 • Cirrhosis (usually nl or mild degree of elevation)

 • Other: Autoimmune Hepatitis (AIH), Celiac disease, Hemochromatosis, A1AT, Wilson’s, Congestive hepatopathy

Extreme AST/ALT elevation, e.g., >1000 (acute processes):

 • Ischemia – e.g. shock, cardiac arrest, Budd-Chiari

 • Meds/toxins – e.g. acetaminophen overdose

 • Acute viral infection – hepatitis A-E, HSV, VZV, EBV, CMV

 • Acute biliary obstruction

 • Rarer causes: autoimmune hep, acute Wilson’s, HELLP syndrome, alcoholic hep, malignant infiltration

2. Causes of cholestatic injury pattern (↑ALK and bili; R ratio<2):

 • Bile duct obstruction – choledocholithiasis, malignancy (cholangio, pancreatic, ampullary), ascending cholangitis, primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC), chronic pancreatitis with strictures

 • Hepatitis in general – usually also with AST/ALT elevation

 • Cirrhosis – e.g. MELD score includes bili

 • Meds/toxins – meds: anabolic steroids, allopurinol, amox/clav, cephalosporins, captopril, carbamazepine, diltiazem, erythromycin, estrogens, TPN, TMP-SMX

3. Causes of infiltrative pattern (primarily ALK-P elevation): 

First send GGT, if ↑likely hepatic, can also test fractionated ALK-P (bone, gut, hepatic)

 • Sarcoidosis or other granulomatous disease (e.g. TB, certain fungal infxns)

 • Amyloidosis

 • Malignancy: lymphoma, metastasis to liver, HCC

 • Hepatic extramedullary hematopoiesis

4. Non-hepatic causes of abnormal LFTs:

 • Indirect hyperbilirubinemia – Gilbert’s syndrome (5% of population), hemolysis, resorption of large hematoma

 • Alk phos elevation – ALK-P is also expressed in bone (e.g. ↑ in Paget’s, bony mets), intestines (e.g., ↑ in SBO), and placenta (third trimester pregnancy)

 • AST elevation – AST is most abundant in liver tissue but also present in muscle (e.g., ↑ rhabdomyolysis, heat stroke, acute MI), kidney, brain, and RBCs

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