Table 2.
Limitations of current non-invasive serum and imaging tests.
| Type of limitation | Serum biomarkers | Transient elastography (VCTE) | Shear wave elastography | MRE |
|---|---|---|---|---|
| Technical limitations | Not Liver specific | Requires training and experience for validated quality criteria No B-mode image and unable to select liver region of interest |
Requires dedicated US training Quality criteria not yet validated Unable to compare reported parameters of shear wave speed (range 0.5–4.4 m/s) or Young's modulus (2–150 kPa) between US devices, VCTE, or MRE |
Requires specialised technician or radiologist |
| Discrimination of adjacent fibrosis stages | No | No | No | No |
| Performance for intermediate fibrosis stage | Poor | Overlapping LSM range | Limited data | Overlapping LSM range |
| Cost and availability | Patented marker panels not readily available and costly | Not widely reimbursed Access concerns in resource limited practices |
Not readily available outside specialised centres | Costly Not available outside dedicated radiology centres |
| False positivity | Haemolysis, Gilbert's disease, cholestasis, immune thrombocytopenia, inflammation, age, exercise, non-fasting | Acute hepatitis, inflammation, non-fasting, exercise, hepatic venous congestion, inflammation or infiltration, alcohol excess, cholestasis, steatosis, portal vein thrombosis | Left vs. Right hepatic lobe, acute hepatitis, hepatic inflammation or infiltration, non-fasting, exercise, right heart failure, extrahepatic cholestasis, breathing cycle (end-expiration vs. end-inspiration) | Inflammation, cholestasis, hepatic venous congestion, postprandial state, and right heart failure |
| Failure | Indeterminate “grey zone” scores in 30-50% for simple markers (NFS, APRI, FIB-4) | Higher failure rates than serum tests: operator inexperience, narrow intercostal space, body habitus, ascites | Higher failure rates than serum tests: BMI, tissue depth >2–3 cm below skin surface | Higher failure than serum tests: waist circumference/BMI, claustrophobia, iron deposition, massive ascites, higher field strength (3 T vs. 1.5 T) |
| Thresholds | Variable for simple markers across aetiologies | Variable across aetiologies | Not validated across aetiologies | Vary between gradient-recalled echo vs. echo planar imaging, 2D vs. 3D acquisition, 40 vs. 60 Hz, and across aetiologies |
| Differentiation between simple steatosis and NASH | No | No | No | No |
| Follow-up of dynamic fibrosis changes | No | No | No | No |
APRI, AST-platelet ratio index; AST, aspartate aminotransferase; BMI, body mass index; CLD, chronic liver disease; FIB-4, fibrosis-4; LSM, liver stiffness measurement; MRE, Magnetic resonance elastography; NAFLD, non-alcoholic fatty liver disease; NFS, NAFLD fibrosis score; US, ultrasound; VCTE, vibration-controlled transient elastography.