Abnormal Liver Tests

General Overview

Hepatocellular pattern
- Disproportionate elevation of AST and ALT compared with alkaline phosphatase
- AST : ALT >2 (with elevated GGT), consider Alcohol
Cholestatic pattern
- Disproportionate elevation in alkaline phosphatase compared with AST and ALT
  - Painful (stone/infection) vs. painless (tumour)
Mixed pattern
Isolated hyperbilirubinemia (with normal serum AST/ALT/ALP)

R=(𝐴𝐿𝑇 ÷ 𝐴𝐿𝑇 𝑈𝐿𝑁)/(𝐴𝐿𝐾 ÷𝐴𝐿𝐾 𝑈𝐿𝑁)
- R > 4 Hepatocellular injury
- R < 2 Cholestatic injury
- R 2-5 Mixed pattern
- Note: All of these patterns may have elevated bilirubin

History, Physical
- Risk of fatty liver, viral hepatitis
- Signs of liver failure
Discontinue hepatotoxic medications and alcohol
Find underlying cause:

CBC/platelet, AST/ALT, Alk Phos, Total Bili, Albumin, PT/INR
HBsAg, HBcAb, HBsAb, HCV Ab (with PCR if positive), iron panel, abdominal ultrasound r/o fatty liver
- If mild elevation and history of alcohol consumption, can repeat initial testing after 3-6 months before moving on to additional testing
Autoimmune: ANA, ASMA, Anti-LKM, IgG
Ceruloplasmin (Wilson), Anti-TTG (with total IgA), TSH, alpha-1 antitrypsin level (phenotyping if indicated)
May consider muscle disorder (CK or aldolase), tick-borne, adrenal insufficiency
Refer to hepatologist for liver biopsy
- If mild elevation may consider expectant management rather than referral
- Refer immediately of acute liver failure for possible transplant

r/o pregnancy, r/o postprandial (<2x ULN, repeat 12h fasting)
Elevated GGT confirms hepatic
- RUQ ultrasonography
  - Common obstructive causes:
    - Intrahepatic (absence of dilatation)
      - PBC, PSC, infiltrative disease, drug (androgenic steroids, phenytoin)
    - Extrahepatic (biliary dilatation)
      - Bile duct stone (choledocholithiasis), PSC, malignancy
If GGT low, consider bone/placenta (pregnancy)
- Calcium, PTH, 25-hydroxy Vit D, Bone scan

Elevated GGT with normal liver biochemical tests including ALP should not lead to an exhaustive work-up

see Jaundice in pediatrics

Unconjugated hyperbilirubinemia
- Overproduction (hemolysis)
  - Hypersplenism
  - G6PD, Thalassemia, Sickle cell, spherocytosis, elliptocytosis, malaria
  - Drug-induced/auto-immune
- Impaired hepatic uptake
  - Portosystemic shunt
  - Drugs (Rifampin)
- Impaired conjugation
  - Hyperthyroidism, hepatitis, Wilson's
  - Gilbert or Crigler-Najar (LFT normal, no evidence of hemolysis/sepsis)
    - History of jaundice during stress/fasting
- Stressor (sepsis) may act on all the above
Conjugated hyperbilirubinemia
- Elevated ALP/GGT
  - Biliary obstruction (eg, gallstones, tumor)
- Elevated ALT/AST
  - Liver disease causing hepatocellular dysfunction (eg, hepatitis, sepsis, or hepatotoxic drugs)
- Normal ALP/GGT
  - Inherited disorders (eg, Dubin Johnson or Rotor syndrome)

References: