The commonest reason advanced fibrosis is missed in metabolic liver disease is a normal transaminase. Aminotransferases correlate poorly with fibrosis stage, and a substantial share of patients with F3 disease have an ALT inside the reference range — a range itself derived from populations that included people with undiagnosed steatosis.
So do not use ALT as the trigger. Use the risk factors: type 2 diabetes, obesity, metabolic syndrome, or steatosis found incidentally on imaging. In any of those, calculate a FIB-4 — it needs only age, AST, ALT and platelet count, all of which you already have — and act on the result rather than on the enzyme.
FIB-4 below 1.3 reliably rules out advanced fibrosis in primary care and needs only repeating in a few years. Above 2.67 warrants specialist referral. The indeterminate middle is where a second test belongs: transient elastography where available, or an enhanced liver fibrosis score. The failure mode this avoids is the patient reassured for a decade by normal liver enzymes who presents with varices.
- Calculate FIB-4 in every patient with type 2 diabetes or obesity, whatever the ALT.
- Treat FIB-4 below 1.3 as reassuring and repeat it in two to three years rather than annually.
- Refer FIB-4 above 2.67; use a second-line test for the indeterminate range.
- Remember FIB-4 performs poorly under 35 and over 65 — interpret it with age in mind.
- Exclude other causes before attributing fibrosis to metabolic disease: alcohol, hepatitis B and C, and drug history all still need asking about.
Why it matters
A normal transaminase is the most frequent reason a patient with F3 fibrosis is told their liver is fine.
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