Clinical applications, limitations and future role of transient elastography in the management of liver disease

Table 1 Optimal cut-off values for liver stiffness measurement in different etiologies of chronic liver disease

	Optimal cut-off LSM for F2	Optimal cut-off LSM for F3	Optimal cut-off for LSM F4	Ref.
Chronic hepatitis C	7.6 (5.1-10.1)	10.9 (8.0-15.4)	15.3 (11.9-26.5)	[33]
Chronic hepatitis B	7.0 (6.9-7.2)	8.2 (7.3-9.0)	11.3 (9.0-13.4)	[33]
Alcoholic liver disease	8.9 (2.8-46.4)	10.3 (7.7-20.8)	18.4 (12.2-75.0)	[66]
Non-alcoholic fatty liver disease	7.0 (6.7-7.8)	8.7 (7.1-10.4)	10.3 (10.3-22.3)	[35-37]
Cholestatic liver disease	7.3	9.8	17.3	[54]

LSM: Liver stiffness measurement.

Table 2 What the clinician needs to know about transient elastography (Fibroscan^®)

1 Clinical indications for TE
Liver disease	Indications for TE	Potential clinical applications
Chronic liver disease	To assess for severity of fibrosis	Assist in treatment decisions in CHC and CHB
		Selection of patients for treatment trials
		Decision to continue or stop MTX
	To diagnose early cirrhosis	Commence variceal screening and HCC surveillance, monitor for decompensation
	Longitudinal assessment of fibrosis	Assess for progression of fibrosis in untreated patients and for regression of fibrosis/cirrhosis in treated patients
Patients with NAFLD	Assess severity of fibrosis and steatosis (with Fibroscan-CAP)	Aggressive control of risk factors
		Selection of patients for treatment trials
		Selection of patients for liver biopsy
Post-liver transplant	Assess for fibrosis in recurrent CHC post liver transplant	Avoid protocol liver biopsies for diagnosis of fibrosis
Non-cirrhotic portal hypertension	Exclude cirrhosis	Assists in differentiating cirrhotic vs non-cirrhotic portal hypertension
Patients with cirrhosis	Predict significant portal hypertension and risk of liver-related events	Stratify frequency of follow-up in low-risk vs high-risk cirrhotics
	Predict absence of varices	Avoid/delay endoscopy screening in cirrhotics at low risk for varices
2 Conditions that affect accuracy of TE
Condition	How it affects the TE result	What the clinician should do
Post-meal	LSMs are elevated after meals due to increased hepatic venous flow	Patients should fast for at least 3 h before TE measurement
Elevated ALT	LSMs are elevated due to hepatic inflammation	Repeat or delay TE till after ALT has returned to baseline/normal levels
		Use ALT-based LSM cut-off values to interpret LSM result
		Use probability-based LSM interpretation scores which account for ALT
Cardiac failure	LSMs are elevated due to hepatic congestion in right heart failure	Repeat or delay TE until after patient’s heart failure is treated
Cholestasis	LSMs are elevated due to increased stiffness from biliary dilatation	Repeat or delay TE until after biliary obstruction is resolved
Operator experience	Operator inexperience may lead to higher rate of unsuccessful or invalid LSM results	TE should be performed by operators with prior experience of at least 50-100 examinations
Obesity	Higher rate of unsuccessful LSMs due to increased SCD because of increased subcutaneous fat	Use XL probe if SCD > 3.4 cm (with the current Fibroscan 502 Touch®, the machine will automatically advise when the XL probe should be used)
		If LSM is unsuccessful with XL probe, use alternative non-invasive test
Ascites	High rate of unsuccessful LSM due to interruption of shear waves by ascites	Use alternative non-invasive test
Pregnancy, cardiac pacemaker, AICD	Safety of TE in these conditions have not been assessed	TE contraindicated

TE: Transient elastography; CHC: Chronic hepatitis C; CHB: Chronic hepatitis B; MTX: Methotrexate; HCC: Hepatocellular carcinoma; CAP: Controlled attenuation parameter; NAFLD: Non-alcoholic fatty liver disease; LSM: Liver stiffness measurement; ALT: Alanine transaminase; SCD: Skin-capsule distance; AICD: Activation-induced cell death.

Table 3 Comparison of non-invasive modalities for assessment of fibrosis

Non-invasive test	Advantages	Disadvantages
Transient elastography	Easy to perform	Requires costly equipment
	Painless and comfortable	Unreliable in patients with severe obesity and ascites
	Can be done in clinic or office	Requires technical expertise
	Provides immediate results for clinician	Requires fasting
	Well-validated	Interpretation of LSM result dependent on etiology, ALT, etc.
	Can be performed reliably in obese patients with the use of XL probe	Only assesses part of the liver
	Readily available in most centres
Serum markers	Easy to perform	Results can be confounded by biochemical abnormalities
	Inexpensive	Indirect reflection of liver fibrosis
	Does not require training or equipment	Does not assess liver stiffness directly
	Well-validated	Some tests are proprietary and are relatively costly
	Easily repeatable
MRE	Multi-dimensional assessment	High cost
	Able to assess whole liver	Limited availability
	Operator independence	Cannot be performed in subjects with claustrophobia
	Can be performed in obese patients and those with ascites	Long examination time
	Can be integrated as part of a comprehensive MRI examination	Cannot be performed in livers with iron overload
ARFI/SWE	Higher success rate compared to TE (using M probe)	Requires special equipment and technical expertise
	Similar accuracy to TE	Operator-dependent
	Can be performed in obese patients and those with ascites	Not widely available
	Can assess whole liver
	Can assess specific part of the liver (i.e., region of interest)

TE: Transient elastography; MRE: Magnetic resonance elastography; ARFI: Acoustic radiation force impulse; SWE: Shear wave elastography; LSM: Liver stiffness measurement; ALT: Alanine transaminase; MRI: Magnetic resonance imaging.