Laboratory tests - liver screen
When to send it
- The panel sent when LFTs are persistently abnormal and the cause is not obvious
- *Order it AFTER the history* - alcohol quantified, every drug/supplement/herbal, metabolic risk, travel, transfusion, tattoos, IVDU, family history
- Always paired with an ultrasound
- Repeat borderline LFTs first - ~30% normalise
Yield
- MASLD is the answer in the majority of Australian liver screens - diagnosed by exclusion plus metabolic risk factors
- Positive yield of the full panel for a treatable specific diagnosis: ~10-20%
- Chronic hepatitis B: ~1% of Australians, concentrated in people born overseas (>60% undiagnosed at some point)
Mechanisms targeted
- Each test targets a specific mechanism of chronic injury:
- Viral - ongoing hepatocyte infection and immune-mediated killing
- Autoimmune - loss of tolerance to hepatocyte (AIH) or biliary epithelial (PBC) antigens
- Metabolic/storage - iron (HFE), copper (ATP7B), protease imbalance (alpha-1 antitrypsin)
- Vascular/congestive - raised sinusoidal pressure
- The point is that most of these are treatable and a few are curable - which is why a full screen is worth doing once, properly
The core panel
| Test | Looking for | Notes |
|---|---|---|
| HBsAg, anti-HBc, anti-HBs | Hepatitis B | anti-HBc alone = occult/resolved - matters before immunosuppression |
| Anti-HCV (then HCV RNA if positive) | Hepatitis C | Antibody persists after cure - RNA confirms active infection |
| CMV, EBV serology | Acute hepatitic picture | Usually only in acute presentations |
| Anti-mitochondrial antibody (AMA-M2) + IgM | PBC | Sensitivity and specificity >95%; with a cholestatic picture, biopsy is unnecessary |
| ANA, anti-smooth muscle (anti-actin), anti-LKM-1 + IgG | Autoimmune hepatitis | Raised IgG is as important as the antibody |
| ANCA (atypical pANCA) | PSC - positive in ~80% | Non-specific; MRCP is the diagnostic test |
| Ferritin + transferrin saturation | Haemochromatosis | Ferritin alone is useless - it rises in alcohol, MASLD and any inflammation |
| Caeruloplasmin (+ 24h urinary copper, slit lamp) | Wilson disease | *Test everyone under 40 with unexplained liver disease* |
| Alpha-1 antitrypsin level + phenotype | A1AT deficiency (PiZZ) | Level is an acute phase reactant - falsely normal in inflammation; get the phenotype |
| Coeliac serology (tTG-IgA + total IgA) | Coeliac transaminitis | Normalises on a gluten-free diet |
| TSH | Thyroid disease | Both hyper and hypo raise LFTs |
| IgG4 | IgG4-related sclerosing cholangitis | Steroid-responsive; mimics cholangiocarcinoma |
| Tumour markers - AFP (+ CA19-9 if cholestatic) | HCC, cholangiocarcinoma | Both are raised by benign disease - interpret with imaging |
Synthetic function and portal hypertension
- INR, albumin, platelets - thrombocytopenia is often the first clue to portal hypertension
- Fibrosis assessment: FIB-4 first, then elastography
Imaging
- Ultrasound with Doppler in everyone - steatosis, nodularity, splenomegaly, ascites, focal lesions, portal/hepatic vein patency (Budd-Chiari)
- MRCP if cholestatic
- Echocardiogram if congestive hepatopathy is possible
Biopsy
- Only if the screen is negative and the abnormality persists, if two diagnoses coexist, or if staging changes management
Interpret by the pattern
- Hepatocellular + negative screen + metabolic risk factors -> MASLD -> the work is fibrosis staging and cardiometabolic risk, not more liver tests
- Hepatocellular + raised IgG + ANA/SMA -> autoimmune hepatitis -> biopsy, then prednisolone + azathioprine
- Cholestatic + AMA positive + raised ALP -> PBC -> ursodeoxycholic acid 13-15 mg/kg/day, then obeticholic acid or a fibrate if inadequate response (POISE/Paris II criteria at 12 months)
- Cholestatic + ANCA + IBD -> MRCP for PSC -> no disease-modifying therapy; annual colonoscopy and biliary/gallbladder surveillance
- HBsAg positive -> HBeAg/anti-HBe, HBV DNA, fibrosis staging, HDV serology, HCC surveillance in defined groups
- HCV RNA positive -> direct-acting antivirals, GP-prescribable in Australia, cure >95%
- Ferritin + transferrin saturation raised -> HFE genotype
- Low caeruloplasmin -> 24h urinary copper, slit lamp for Kayser-Fleischer rings, ATP7B sequencing
Always, regardless of cause
- Alcohol minimisation, weight loss, metabolic risk factor treatment
- Vaccinate against hepatitis A and B
- Medication review - the commonest reversible contributor
- HCC surveillance (6-monthly ultrasound +/- AFP) once cirrhotic, and in defined chronic hepatitis B groups even without cirrhosis
Associations
- Metabolic syndrome, T2DM, obesity, OSA - MASLD
- IBD - PSC
- Sjogren, autoimmune thyroid disease, coeliac, RA - PBC and AIH
- Emphysema in a young non-smoker - alpha-1 antitrypsin deficiency
- Neuropsychiatric symptoms, haemolysis, Fanconi syndrome in a young person - Wilson disease
- Right heart failure, constrictive pericarditis, Fontan - congestive hepatopathy
- Thrombophilia, myeloproliferative neoplasm (JAK2), oral contraceptive, pregnancy - Budd-Chiari
- Migration from a hepatitis B or C endemic country
After the screen
- A negative screen does not end the problem - repeat in 3-6 months; MASLD and drug injury are diagnoses of exclusion over time
- Once a cause is found, the prognosis depends on the fibrosis stage, not the aetiology
- Curable/controllable if caught: hepatitis C (cure), hepatitis B (suppression), haemochromatosis (venesection), Wilson (chelation), AIH (immunosuppression), PBC (UDCA)
- The justification for a complete screen is that most of these are silent until cirrhosis
- Two diagnoses coexist more often than expected - alcohol + MASLD (MetALD), HBV + HDV, AIH + PBC overlap
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