Interpretation of liver function tests

Interpretation > Blood

Patterns

Acute hepatitic picture: ALT/AST in 1000s, ALP mildly raised
Chronic hepatitic picture: ALT/AST in 100s
Cholestatic (obstructive) picture: ALP significantly raised, ALT/AST mildly raised, ↑bilirubin
Alcoholic: ↑γGT, ↑mean corpuscular volume, AST/ALT mildly elevated (AST>ALT), ↑bilirubin in acute alcoholic hepatitis (may be disproportionate to ALT/AST)
Cirrhosis/chronic liver disease: liver enzymes may be normal, ↓albumin, ↑coagulation tests

Liver enzymes

Enzymes leak from damaged liver cells and therefore they reflect liver injury (not function).

Aminotransferases – alanine aminotransferase (ALT) and aspartate aminotransferase (AST)

ALT sources: specific to liver
AST sources: liver, heart, skeletal muscle, kidneys, pancreas
Marked increase (>1000):
- Toxin-/drug-induced hepatitis (e.g. paracetamol)
- Acute viral hepatitis (Hep A/B/E, EBV, CMV)
- Liver ischaemia
Modest increase (300-500): chronic viral/alcoholic/autoimmune hepatitis, biliary obstruction
Mild increase (<300): cirrhosis, non-alcoholic fatty liver disease, hepatocellular carcinoma, haemochromatosis/Wilson’s, cardiac
Ratio of ALT:AST
- ALT>AST: chronic liver disease
- AST>ALT: + in established cirrhosis, ++ in alcoholic liver disease

Alkaline phosphatase (ALP)

Main sources: biliary ducts, bone (Paget’s disease, bony metastasis, fractures, osteomalacia, renal bone disease)

Lesser sources: placenta (pregnancy), small intestine (fatty meals), kidneys (chronic kidney disease)

Isoenzyme analysis can confirm

Marked increase (>4x normal): cholestasis (e.g. gallstones, pancreatic cancer, primary biliary cholangitis, primary sclerosing cholangitis, drugs, strictures)

Moderate increase (<3x normal): hepatitis, cirrhosis, infiltration (e.g. hepatocellular carcinoma, liver abscess etc.)

Gamma-glutamyltransferase (γGT)

Mirrors ALP so can be used to confirm if a rise in ALP is of hepatic origin

Raised with alcohol abuse and enzyme-inducing drugs

Bilirubin

Extravascular haemolysis results in breakdown of Hb → globulin (further broken down into amino acids) + haem (further broken down into bilirubin). This unconjugated bilirubin is then conjugated by the liver so it can be excreted in bile. In advanced liver disease, the liver retains its ability to conjugate bilirubin, but it cannot excrete it.

Normal bilirubin values (µmol/L)
Total	≤20
Indirect (unconjugated)	≤15
Direct (conjugated)	≤5

Unconjugated hyperbilirubinaemia: increased ‘indirect’ bilirubin (unconjugated = indirect)
- Increased red blood cell breakdown (haemolytic anaemia)
- Impaired hepatic uptake (drugs, heart failure)
- Impaired conjugation (Gilbert’s syndrome, physiological neonatal jaundice)
Mixed hyperbilirubinaemia
- Hepatocellular dysfunction (liver disease)
Conjugated hyperbilirubinaemia: increased

Functional liver tests

Albumin

Albumin makes up more than half of the total protein in the blood. The remainder is made up by globulins (other blood proteins) which include α1-globulins (α1-antitrypsin), α2-globulins (α2-macroglobulin, haptoglobin), β-globulins (complement, transferrin), and γ-globulins (immunoglobulins). Albumin is synthesised by the liver and has a half-life of around 20 days. Hence, changes in levels happen over weeks.

↓albumin + ↓total protein = cirrhosis, nephrotic syndrome, chronic inflammation, protein-losing enteropathy, alcoholism, protein malnutrition/malabsorption
↓albumin + normal total protein = infection (albumin is a negative acute phase protein)
↓albumin + ↑ total protein = myeloma, Waldenström’s

Prothrombin time/INR

PT/INR depend on clotting factors and fibrinogen which are synthesised by the liver. Some clotting factors have short half-lives (e.g. 6-8 hours) so changes can occur rapidly.

Raised PT/INR: liver disease (with impaired function), vitamin K deficiency, consumptive coagulopathy (e.g. disseminated intravascular coagulation)

Other tests

FBC clues

Anaemia = GI bleeding
Macrocytosis = alcohol
Thrombocytopenia = effect of alcohol on bone marrow, hypersplenism, liver cirrhosis or disseminated intravascular coagulation

Further investigations to find cause

Blood tests

Viral
- Viral hepatitides: hepatitis A IgM, hepatitis B surface antigen, hepatitis C IgG, hepatitis E IgM
- CMV serology
- EBV serology
Autoimmune liver screen
- Anti-smooth muscle (autoimmune hepatitis type 1)
- Anti-mitochondrial (primary biliary cholangitis)
- Anti-liver-kidney microsomal (autoimmune hepatitis type 2, hepatitis C/D, drug-induced hepatitis)
- Antinuclear (autoimmune hepatitis type 1, SLE)
Tumour markers – if cirrhosis/weight loss
- α- fetoprotein (hepatocellular carcinoma)
Infiltrative
- Ferritin and transferrin saturation (haemochromatosis) – but be aware ferritin is also an acute phase protein
- Serum copper and caeruloplasmin ± 24-hour urinary copper (Wilson’s disease)
- Fasting glucose and lipids (fatty liver disease)
Metabolic
- α₁-antitrypsin (α₁-antitrypsin deficiency)
- Immunoglobulins and protein electrophoresis (IgM raised in primary biliary cholangitis, IgA raised in alcoholic liver disease, IgG raised in autoimmune hepatitis)
- Tissue transglutaminase antibody (coeliac disease)
Toxins
- Paracetamol level (paracetamol overdose)

Imaging

Abdominal ultrasound: first line imaging (quick and cheap) that is useful for determining liver texture, size and presence of any gallstones or cholecystitis
Abdominal CT: can confirm pancreatitis or tumour
Elastography: grades liver fibrosis in chronic liver disease non-invasively
Magnetic resonance cholangiopancreatography: to look for duct disease/stones if ultrasound normal

Procedures

Ascitic tap: if ascites present
Liver biopsy (CT-guided usually, but done trans-jugular if there is ascites or coagulopathy)

Some non-hepatic causes of deranged LFTs

In addition to any described above:

Drugs
- Hepatitis: tuberculosis antibiotics (rifampicin/isoniazid/pyrazinamide), sodium valproate, methotrexate, methyldopa, amiodarone, statins, paracetamol, phenytoin, ketoconazole/fluconazole, nitrofurantoin, sulfonylureas/sulfonamides
- Cholestasis: co-amoxiclav (may be delayed/severe), clarithromycin/erythromycin, carbamazepine, chlorpromazine, contraceptives, flucloxacillin, sulfonylureas/sulfonamides
Right heart failure
Sepsis
Coeliac disease
Haemolysis
Hyperthyroidism
Right lower lobe pneumonia

Try some scenarios

Find the normal lab values here.

A 17 year old student presents with a fever and sore throat. He has cervical lymphadenopathy. His full blood count shows a lymphocytosis. Liver function tests reveal: ALT 1020, ALP 130, Bilirubin 27, Albumin 36.

Which pattern of LFT derangement is present?

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Which further tests would you consider?

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What is the likely diagnosis?

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How would you manage the patient?

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A 20 year old female with severe depression and bipolar disorder presented to the acute medical unit after a paracetamol overdose. Her paracetamol level is checked and is over the treatment line. Her ALT is 62 but her other liver function tests are normal.

Which treatment would you administer?

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Which blood tests are the most important to check at the end of the infusion?

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If the patient refused the treatment and tried to leave, what would you do? She seems to understand the risks of the decision.

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A 54 year old who drinks 1L vodka daily, presents with vomiting. On examination, he seems to be tremulous and is confused. He has large volume ascites. His blood tests are taken and his liver function tests are as follows: ALT 122, ALP 22, Bilirubin 120, Albumin 22. His coagulation test reveals: INR 3.0. His renal function test reveals: Na⁺ 128, K⁺ 4, Ur 6, Cr 190.

What do you think is going on?

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What is your initial management?

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An ascitic fluid aspirate is taken and the ascitic white cell count is raised. What are you concerned about and what additional treatments would you administer?

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Interpretation of liver function tests

Patterns

Liver enzymes

Bilirubin

Functional liver tests

Other tests

FBC clues

Further investigations to find cause

Blood tests

Imaging

Procedures

Some non-hepatic causes of deranged LFTs

Try some scenarios

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