FIB-4 vs FibroScan: how the two tests work together

What FIB-4 and FibroScan each measure

FIB-4 and FibroScan measure fibrosis in completely different ways. FIB-4, from Sterling and colleagues in 2006, is an index calculated from age, AST, ALT and platelet count: (age × AST) / (platelets × √ALT). It costs nothing beyond routine blood tests and can be worked out in any clinic. FibroScan is a brand of vibration-controlled transient elastography (VCTE). A probe on the skin over the liver sends a mechanical pulse into the tissue and times how fast the resulting shear wave travels, and the device reports liver stiffness in kilopascals (kPa); stiffer, more fibrotic liver carries the wave faster. FibroScan can also report the controlled attenuation parameter (CAP), a measure of liver fat. So FIB-4 infers fibrosis from its effects on blood tests, while FibroScan measures a physical property of the liver itself. That is why FIB-4 suits first-line screening of many people, and FibroScan suits the smaller group that FIB-4 cannot clear.

Which test is more accurate?

FibroScan is more accurate than FIB-4 for advanced fibrosis, but neither is perfect, and they work best together. Mózes and colleagues pooled individual data from 37 studies with 5,735 patients with non-alcoholic fatty liver disease who had both VCTE and a liver biopsy, published in Gut in 2022. Median age was 54, median body mass index 30, a third had type 2 diabetes and 30% had advanced fibrosis. The area under the ROC curve for advanced fibrosis was 0.85 for liver stiffness by VCTE, 0.76 for FIB-4 and 0.73 for the NAFLD Fibrosis Score. The 2023 AASLD practice guidance reaches the same conclusion: FIB-4 is statistically inferior to elastography and to serum panels such as the Enhanced Liver Fibrosis (ELF) test, but it is still recommended first because it is cheap, widely available and good at identifying people with a low probability of advanced fibrosis. Its strength is ruling out; FibroScan adds accuracy where FIB-4 is unclear.

The two-step pathway and its cut-offs

The 2023 AASLD guidance on fatty liver disease uses FIB-4 as the first step and VCTE or ELF as the second for anyone FIB-4 does not clear. A FIB-4 under 1.3 is low risk, and patients can be managed in primary care, with FIB-4 repeated every 1 to 2 years in those with prediabetes, type 2 diabetes or two or more metabolic risk factors. A FIB-4 of 1.3 or more leads to the second test. On VCTE, a liver stiffness under 8 kPa rules out advanced fibrosis, 8 to 12 kPa may be associated with fibrotic steatohepatitis, and over 12 kPa is associated with a high likelihood of advanced fibrosis, although the positive predictive value is low, 0.34 to 0.71. The matching ELF cut-offs are under 7.7 and 9.8 or more. AASLD advises considering direct referral to hepatology when FIB-4 is over 2.67.

In the Mózes analysis, FIB-4 (under 1.3, 2.67 or more) followed by VCTE (under 8.0, 10.0 kPa or more) gave a sensitivity of 66% and a specificity of 86% for advanced fibrosis, with 33% of patients still needing a biopsy for a final answer.

When each test misleads

FIB-4 and FibroScan fail for different reasons, which is one more reason to use them in sequence. FIB-4 depends on age, AST and platelets, so it reads falsely high at 65 and over (where AASLD uses a cut-off of 2.0 instead of 1.3), after a recent AST rise, or when platelets are low for another reason, and the AASLD guidance says it should not be used in acutely ill patients and performs less well in type 2 diabetes. FibroScan measures stiffness, and AASLD notes that liver stiffness rises not only with fibrosis but also with passive congestion, marked inflammation and infiltrative diseases, so heart failure or a hepatitis flare can push the reading up. VCTE and magnetic resonance elastography (MRE) both report kilopascals, but on different scales, so an MRE value cannot be read against VCTE cut-offs. When the two tests disagree, or both are indeterminate, AASLD suggests MRI-based tests or a liver biopsy.

Worked example

Take a 58-year-old with type 2 diabetes and a fatty liver on ultrasound, an AST of 48 U/L, an ALT of 40 U/L and a platelet count of 180 × 10⁹/L. FIB-4 is (58 × 48) / (180 × √40) = 2,784 / 1,138 = 2.45. That is above 1.3 and below 2.67, the indeterminate band, so FIB-4 alone can neither clear nor confirm advanced fibrosis, and the AASLD pathway calls for a second test. A FibroScan reading of 6.5 kPa would be under 8 kPa and rule out advanced fibrosis, returning the patient to primary care follow-up with FIB-4 repeated every 1 to 2 years. A reading of 13.5 kPa would be over 12 kPa, a high likelihood of advanced fibrosis, warranting specialist assessment. A reading of 9.5 kPa would sit in the 8 to 12 kPa zone, where MRI-based testing or specialist review helps settle the stage. In each case the FibroScan result, not the FIB-4, decides the next step.

Start with step one in the FIB-4 calculator, which applies the MASLD, age 65 and HIV/HCV cut-offs.