Patients with chronic liver disease (CLD) often require diagnostic assessment of the liver injury. Liver biopsy remains a promising method for the assessment of necro-inflammation and fibrosis, but the inherent limitations are many. The development of several non-invasive tests (NITs) has brought new hope to patients with CLD.

NITs may be-

• biological (serum biomarker algorithms) or,
• physical (imaging assessment of tissue stiffness) assessments.

Nevertheless, these NITs too possess several limitations in terms of variability, inadequate accuracy and risk for errors.

A paper by Patel K. and Sebastiani G. explains all the NIVs methods and their limitations in clinical practice.

Limitations of Serum biomarkers-

• Not Liver-specific
• Can’t discriminate adjacent fibrosis stages
• Poor Performance for intermediate fibrosis stage
• Costly and arent readily available
• False-positive for- Haemolysis, Gilbert’s disease, cholestasis, immune thrombocytopenia, inflammation, age, exercise, nonfasting
• Shows failure as- indeterminate “grey zone” scores in 30-50% for simple markers (NFS, APRI, FIB-4)
• The threshold remains variable for simple markers across aetiologies
• Cant differentiate between simple steatosis and NASH
• Follow-up of dynamic fibrosis changes isnt possible

Limitations of Transient elastography (vibration-controlled transient elastography or VCTE)-

• Demands technical training and experience for validated quality criteria 
• Can’t provide B-mode image and inability to select the liver region of interest
• Discrimination of adjacent fibrosis stages isnt possible
• Overlapping LSM(liver stiffness measurement) range for intermediate fibrosis stage
• Not very economic and not readily available 
• Reports false positivity in Acute hepatitis, inflammation, non-fasting, exercise, hepatic venous congestion, inflammation or infiltration, alcohol excess, cholestasis, steatosis, portal vein thrombosis
• Higher failure rates than serum tests in terms of- operator inexperience, narrow intercostal space, body habitus, ascites
• Thresholds are Variable across aetiologies
• Can’t differentiate between simple steatosis and NASH
• Follow-up of dynamic fibrosis changes isnt possible

Limitations of Shear wave elastography-

• Demands dedicated US training Quality criteria which is not yet validated 
• Inability in comparing 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.
• Discrimination of adjacent fibrosis stages not possible
• Limited Performance for intermediate fibrosis stage
• Not readily available
• Shows false positivity in 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)
• Higher failure rates than serum tests relating to BMI(body mass index), tissue depth >2–3 cm below the skin surface
• Thresholds not validated across aetiologies
• Cant differentiate between simple steatosis and NASH
• Follow-up of dynamic fibrosis changes isnt possible

Limitations of Magnetic resonance elastography (MRE)-

• Requires specialized technician or radiologist for its use
• Discrimination of adjacent fibrosis stages not possible
• Overlapping LSM(liver stiffness measurement) range for intermediate fibrosis stage
• Costly and not readily available
• False positivity in Inflammation, cholestasis, hepatic venous congestion, postprandial state, and right heart failure
• Higher failure than serum tests in reference to- waist circumference/ BMI, claustrophobia, iron deposition, massive ascites, higher field strength (3 T vs. 1.5 T)
• Threshold Vary between gradient recalled echo vs. echo-planar imaging, 2D vs. 3D acquisition, 40 vs. 60 Hz, and across aetiologies
• Cant differentiate between simple steatosis and NASH
• Follow-up of dynamic fibrosis changes isnt possible

Thus it is important to understand the strengths and limitations of these NITs for more judicious interpretation in the clinical context, where they should be treated as complementary rather than as a replacement for liver biopsy.

Source: Patel, K, Sebastiani, G. Limitations of non-invasive tests for assessment of liver fibrosis. JHEP Reports 2020;2. DOI:https://doi.org/10.1016/j.jhepr.2020.100067