Liver Function Tests

Question 1

Evaluation of isolated mild chronic elevation of aminotransferases

Answer 1

1: Initial evaluation
- Review medications, herbal therapies, recreational drugs
- Screen for alcohol abuse
- Obtain hepatitis B and C serologies
- Screen for haemochromatosis
- Evaluate for fatty liver (AST/ALT < 1 and evidence of RUQ sonography)
2: Second-line evaluation
- Consider autoimmune hepatitis (Serum electrophoresis, Obtain ANA and ASMA if +’ve)
- Obtain TFTs
- Consider Coeliac Disease
3: Third-line evaluation
- Wilson Disease
-a1-antitrypsin deficiency (serum a1-antitrypsin level)
- Consider adrenal insufficiency (8am Serum cortisol, plasma ACTH, high-dose ACTH stimulation test)
- Exclude muscle disorders (CK and aldolase)
4: Observe or liver biopsy
- ALT and AST < 2ULN? Observe
- Otherwise, consider liver biopsy

Question 2

Overview of LFTs

Answer 2

Markers of liver injury - ALT, AST, ALP, Bili
Markers of hepatocellular synthetic function - Albumin, Bilirubin, Prothrombin time

Question 3

Alkaline Phosphatase (ALP)

Answer 3

Derived from both liver and bones
- Can be fractionated to determine origin if necessary
- Normal elevations
- Pregnant women in 3rd trimester. (Contributing placental ALP)
- Blood type O or B can have increases after eating fatty meal (influx of intestinal ALP)
- Infants and toddlers can have transient ALP increase
- Diabetes Mellitus
- Children and adolescents due to increased osteoblastic activity
- Cholestasis if > 4* ULN
- Likely liver origin if other LFT derangement
- Bone disease causing bone-origin ALP increase - Healing fractures, osteomalacia, hyperparathyroidism, Paget disease of the bone, hyperthyroidism, osteogenic sarcoma, bone metastases. Test calcium, serum PTH, 25-hydroxy vit D, Bone scintigraphy

• If liver origin likely, follow up test with Liver US to review for cholestasis.

Question 4

Gamma-glutamyl transpeptidase (GGT)

Answer 4

• Found in hepatocytes and biliary epithelial cells
• Also in kidney, seminal vesicles, pancreas, spleen, heart, brain
• Normal full-term neonates has 6-7* upper limit of adult reference range. Levels decline and reach adult levels by 7/12 age
• Lacks specificity in liver disease ( Other causes of increase include MI, pancreatic disease, renal failure, COPD, DM, alcoholism, phenytoin and barbiturate use.
• Use more as adjunct to review for origin of ALP or aminotransferase elevation.

Question 5

Lactate dehydrogenase (LDH)

Answer 5

• Cytoplasmic enzyme present in tissues through the body.
• 5 isoenzymes able to be isolated with electrophoresis
• Slowest migrating band predominates in the liver.
• Not as sensitive as aminotransferases in diagnosis of liver disease
• More useful as a marker in haemolysis

Question 6

Examination findings indicative of liver disease

Answer 6

• Temporal and proximal muscle wasting
• Stigmata of liver disease (spider naevi, palmar erythema, gynaecomastia, caput medusae)
• Ascites - Shifting dullness
• Encephalopathy (Hepatic flap)
• Signs of advanced alcohol cirrhosis - Dupuytren’s contractures, parotid gland enlargement, testicular atrophy
• Hepatic congestion (raised JVP)
• Splenomegaly - Palpable = 2-3x enlarged
• Hepatomegaly or cirrhosis
• Virchow’s node (palpable L supraclavicular lymph node) or sister mary joseph periunbilical nodule are signs of abdominal malignancy

Question 7

Patterns of liver test abnormalities

Answer 7

Hepatocellular - ^ Bili, AST, ALT
Cholestatic - ^ Bili, ALP

IF all are elevated, more likely to be characterised by higher segment (More AST, ALT would be hepatocellular)
- Low albumin, High PTT, High INR suggests chronic process affecting hepatosynthesis.

Question 8

Magnitude of AST and ALT elevations

Answer 8

• Alcoholic fatty liver disease (AST < 8* and ALT < 5* ULN)
• NAFLD (AST AND ALT < 4* ULN)
• Acute viral hepatitis or toxin-related hepatitis with jaundice (AST and ALT > 25* ULN)
• Chronic HCV infection - Normal to 10* ULN. Most likely < 2* ULN
• Chronic HBV Infection - Most likely 2* ULN but can be > 10* ULN
• Acute liver failure - AST and ALT > 10* ULN + High PT and hepatic encephalopathy

Question 9

Alkaline Phosphatase (ALP)

Answer 9

ALP > 4* ULN likely due to hepatic cholestasis

Question 10

Isolated hyperbilirubinaemia

Answer 10

Fractionate bilirubin to determine whether it is unconjugated or conjugated

^ Conjugated = decreased excretion of bile ductules or leakage of pigment from hepatocytes into serum
-
^ Unconjugated = Overproduction, impairment of uptake, impaired conjugation of bilirubin.
- Haemolysis, ineffective erythropoiesis, Gilbert disease, Crigler-Najjar syndrome)
- Gilbert syndrome - Can have jaundice during times of stress or fasting with normal AST/ALT/ALP with mild unconjugate hyperbilirubinaemia (<4mg/dL)