Non-alcoholic fatty liver disease affects approximately 25-30% of the UK adult population. The vast majority have simple steatosis — benign fat accumulation that requires lifestyle modification but not specialist referral. A minority have non-alcoholic steatohepatitis (NASH) with progressive fibrosis that, if undetected, leads to cirrhosis, liver failure, and hepatocellular carcinoma.
The clinical challenge is identifying which patients have progressed to significant fibrosis — because they look identical on blood tests to those with benign steatosis. ALT may be normal or mildly elevated in both groups. Ultrasound shows steatosis in both. The distinguishing investigation is fibrosis assessment — and the NICE NG49 pathway uses non-invasive fibrosis scores as the gateway.
This guide walks through the pathway step by step, with worked examples and links to the relevant calculators on iatroX.
Step 1 — Who Needs Fibrosis Assessment?
NICE NG49 recommends fibrosis assessment for adults with NAFLD — defined as hepatic steatosis on ultrasound in the absence of significant alcohol consumption (>14 units/week) or other causes of liver disease.
In practice, the patients who need assessment are those with incidental findings of fatty liver on ultrasound (often done for other reasons), persistently elevated ALT (>2x upper limit) without other explanation, metabolic syndrome components (obesity, type 2 diabetes, dyslipidaemia, hypertension), and type 2 diabetes specifically (where the prevalence of significant fibrosis is substantially higher — approximately 15-20% have F3-F4 fibrosis).
Step 2 — Calculate FIB-4
The FIB-4 index is the first-line non-invasive fibrosis test in the NICE NG49 pathway. It uses four readily available variables: age, AST, ALT, and platelet count.
Formula: FIB-4 = (Age × AST) / (Platelets × √ALT)
Interpretation (NICE NG49):
- FIB-4 <1.30 — Low risk of advanced fibrosis. Reassure. Lifestyle advice. Repeat in 3 years (or sooner if risk factors change).
- FIB-4 1.30-2.67 — Indeterminate. Further assessment needed (see Step 3).
- FIB-4 >2.67 — High risk of advanced fibrosis. Refer to hepatology.
Worked example: 54-year-old man, AST 38, ALT 52, platelets 210. FIB-4 = (54 × 38) / (210 × √52) = 2052 / (210 × 7.21) = 2052 / 1514 = 1.36 — indeterminate. Proceed to Step 3.
Step 3 — Indeterminate FIB-4: What to Do Next
The indeterminate zone (1.30-2.67) is where most clinical uncertainty lies — and where the AKT most commonly tests. A FIB-4 in this range means the score alone cannot confidently rule in or rule out advanced fibrosis.
NICE NG49 offers two pathways for indeterminate results:
Option A — Calculate NAFLD Fibrosis Score (NFS). The NFS uses age, BMI, impaired fasting glucose/diabetes status, AST, ALT, platelets, and albumin. It provides a second non-invasive estimate that may reclassify the patient into low-risk or high-risk categories.
Calculate NAFLD Fibrosis Score on iatroX.
NFS interpretation: <-1.455 = low risk (reassure). -1.455 to 0.676 = indeterminate. >0.676 = high risk (refer).
Option B — Refer for specialist non-invasive fibrosis assessment. FibroScan (transient elastography) or the Enhanced Liver Fibrosis (ELF) test. These are more accurate than blood-based scores but require specialist access.
Decision logic: If NFS reclassifies the patient into low-risk or high-risk, act accordingly. If NFS is also indeterminate (both FIB-4 and NFS in their indeterminate ranges), refer for FibroScan/ELF. Two indeterminate scores warrant specialist assessment.
Continuing the worked example: NFS for the same patient: age 54, BMI 31, diabetes (yes), AST/ALT ratio 0.73, platelets 210, albumin 38. NFS = -0.6 — indeterminate. Both FIB-4 and NFS are indeterminate. Refer for FibroScan.
Step 4 — When to Refer Directly to Hepatology
Refer directly (bypassing the scoring pathway) if there are clinical signs of chronic liver disease (spider naevi, palmar erythema, splenomegaly, ascites), platelet count <150 (suggests portal hypertension), or FIB-4 >2.67 (high risk).
For patients with type 2 diabetes, consider a lower threshold for referral — the pre-test probability of significant fibrosis is higher in this group, and the consequences of missed fibrosis are more severe because diabetes accelerates progression.
Step 5 — After Referral: What Happens at the Specialist Level
FibroScan results are reported in kilopascals (kPa). <7.0 kPa = no significant fibrosis (F0-F1). 7.0-9.5 kPa = possible significant fibrosis (F2). >9.5 kPa = probable advanced fibrosis (F3-F4). >12.5 kPa = probable cirrhosis (F4).
If cirrhosis is confirmed, staging with Child-Pugh and prognostic assessment with MELD/MELD-Na becomes relevant for determining management intensity and transplant consideration.
The Key Points for AKT and Clinical Practice
FIB-4 is first-line. NAFLD Fibrosis Score is second-line for indeterminate FIB-4 results. Two indeterminate scores warrant specialist referral for FibroScan or ELF. FIB-4 >2.67 warrants direct hepatology referral. Patients with type 2 diabetes have higher pre-test probability and may warrant a lower referral threshold. ALT can be normal in significant fibrosis — do not be falsely reassured by normal transaminases.
All three calculators are available on iatroX Calculators with NICE NG49-referenced interpretation and cross-links between them.