Dr. Josue Flores presented a fascinating case of sub-acute painful jaundice that was caused by an infiltrating lymphoma. Dr. Flores gave us a lot of useful tips for evaluating liver function studies!
Purpose of Liver function tests:
•Detect hepatic disease
•Differentiate among different hepatobiliary disorders
•Measure extent of injury
•Monitor response to therapy
COMPONENTS:
Alanine aminotransferase (ALT)
•Specific marker of hepatocellular injury
Aspartate aminotransferase (AST)
•Found in liver, cardiac muscle, skeletal muscle, kidney, and brain
Alkaline phosphatase
•Found in liver in hepatocytes on canalicular membrane •Pregnancy from placenta •Blood types O and B after fatty meal •Diabetes mellitus •Children and adolescents •Gradually increases from ages 40 to 65
GGT:
•Correlates with alkaline phosphatase
•Found in bile duct epithelial cells
Bilirubin - Reflects hepatic uptake, conjugation and excretory function
Albumin
•Reflects hepatic synthesis
•Correlates with severity of liver dysfunction
•Less sensitive due to 2-3 week half-life
Prothrombin time
•Accurate measure of liver dysfunction due to shorter half life of coagulation factors •Measures II, V, VII, and X
Patterns of Liver Function Abnormalities:
1.Hepatocellular injury
2.Cholestasis
3.Mixed
4.Isolated hyperbilirubinemia
*R ratio = (ALT ÷ ALT ULN) ÷ (ALP ÷ ALP ULN)
•Hepatocellular > 5
•Cholestatic < 2
1. HEPATOCELLULAR INJURY
Classification of liver injury:
•Massive > 10,000
•Severe > 15X
•Moderate 5-15X ULN
•Mild 2-5X ULN
•Borderline < 2x ULN
Highest elevations are seen in:
•Direct hepatoxin exposure e.g. acetaminophen
•Ischemic hepatopathy
•Amanita phalloides
Workup to consider:
•HAV IgM
•HBsAG, HBcAb IgM, HBsAb
•HCV Ab
•HSV, EBV, CMV
•ANA, ASMA, Anti-LKM, IgG
•Ceruloplasmin
•Serum drug panel
•Urine toxicology
•CK and aldolase
•Pregnancy test and UA
•Doppler ultrasound
•+/- n-acetyl cysteine
•If workup is negative, consider liver biopsy
Acute Liver Failure Diagnostic Criteria:
•Aminotransferases > 15x upper limit of normal
•Hepatic encephalopathy
•Prolonged prothrombin time i.e. INR > 1.6
Liver consultation for referral to transplant center
2. CHOLESTASIS
Elevated Alk Phos
•Categorize the cholestasis by anatomy with RUQ ultrasound: Extrahepatic versus Intrahepatic
•Biliary duct dilatation indicates extrahepatic
•If other liver chemistry is normal, obtain GGT or fractionated ALKP
DDx of Cholestasis
•Choledocholithiasis
•Malignancy
•Primary Sclerosing Cholangitis
•Primary Biliary Cholangitis
•Chronic pancreatitis
•HIV/AIDS associated cholangiopathy
Evaluation:
•Endoscopic retrograde cholangiopancreatography (ERCP)
•MRI cholangiopancreatography (MRCP)
•If diagnosis is unclear, obtain liver biopsy
3. MIXED - see above
4. ISOLATED HYPERBILIRUBINEMIA
•Isolated Hyperbilirubinemia
•Fractionate the bilirubin to distinguish between overproduction and defects in uptake or excretion
Unconjugated:
•Overproduction
•Hemolytic disorders
•Impaired uptake
•Impaired excretion
•Gilbert Disease
•Jaundice during stress
•Unconjugated bilirubin < 4 mg/dL
•Crigler-Najjar Syndrome
•Defects in UDP glucuronosyltransferase activity
•Drugs
Conjugated:
Dubin-Johnson Syndrome
•Defect in excretion into bile ducts
Rotor Syndrome
•Defect in re-uptake of bilirubin by hepatocytes •
Typically presents as jaundice in the 2nd decade
They are benign conditions
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