Pattern recognition & investigation guidance for Australian GP
FIB-4 = (Age × AST) ÷ (Platelets × √ALT)
Validated for age ≥ 35. GESA recommends as first-line fibrosis assessment in MAFLD.
| Pattern | Key Features |
|---|---|
| Hepatocellular | ALT/AST ↑↑ predominant (R-factor ≥ 5). Viral, toxic, autoimmune, metabolic. |
| Cholestatic | ALP ↑↑ predominant (R-factor ≤ 2). Obstruction, PBC, PSC, drug-induced. |
| Mixed | R-factor 2–5. Drug reactions, granulomatous, evolving disease. |
| Isolated GGT ↑ | Non-specific. Alcohol, enzyme inducers, MAFLD, obesity. |
| Isolated ALP ↑ | If GGT normal → bone origin. If GGT ↑ → hepatobiliary. |
| Isolated bilirubin ↑ | Gilbert's if unconjugated, mild, LFTs otherwise normal. |
R = (ALT ÷ ALT ULN) ÷ (ALP ÷ ALP ULN)
R ≥ 5 → Hepatocellular
R ≤ 2 → Cholestatic
R 2–5 → Mixed
| Ratio | Suggests |
|---|---|
| < 1 (ALT > AST) | Viral hepatitis, MAFLD, acute toxic injury |
| > 1 | Alcohol, advanced fibrosis/cirrhosis, muscle |
| > 2 (AST < 300) | Strongly suggests alcohol-related liver disease |
| Score | Risk | Action |
|---|---|---|
| < 1.3 | Low | Repeat FIB-4 every 1–3 years |
| 1.3 – 2.67 | Indeterminate | Second-line: Fibroscan (VCTE), ELF, or Hepascore |
| > 2.67 | High | Refer to hepatology / liver clinic |
Age < 35: FIB-4 less validated — interpret with caution.
Age ≥ 65: Consider adjusted lower cutoff of 2.0 (lower specificity at standard cutoff).
Second-line thresholds: VCTE ≥ 8 kPa · ELF ≥ 9.8 · Hepascore ≥ 0.60 → refer to specialist.
| Severity | Repeat Interval |
|---|---|
| Normal | No routine repeat needed |
| Borderline (1–1.5× ULN) | 3–6 months (sooner if clear transient cause identified) |
| Mild (1.5–3× ULN) | 4–6 weeks to confirm persistence |
| Moderate (3–10× ULN) | 4–6 weeks alongside investigation |
| Severe (10–25× ULN) | 1–2 weeks with urgent workup |
| Massive / Urgent (>25× / >500) | 24–72 hours / daily if admitted |
| Isolated GGT ↑ | 3–6 months (address cause first) |
| Isolated bilirubin ↑ (Gilbert's) | No routine repeat needed |
| Isolated ALP ↑ (bone) | As clinically indicated for bone condition |
Key principle: Confirm persistence before committing to a full workup. 16–30% of mildly elevated LFTs normalise on repeat testing. If normalised → likely transient cause → reassure.
Post-investigation: If cause identified and managed (e.g. MAFLD with lifestyle change, medication stopped), repeat in 3–6 months to confirm improvement. If FIB-4 low risk, repeat FIB-4 every 1–3 years (GESA 2024).