Fundamentals of Liver Elastography

2.1 Introduction

The progression from early steatosis through fibrosis to cirrhosis and its complications, including portal hypertension, hepatocellular carcinoma, and liver failure, demands accurate staging for appropriate clinical management (de Franchis et al., 2022; European Association for the Study of the Liver, 2021).

Historically, liver biopsy was the gold standard for assessing liver fibrosis. However, this invasive procedure carries inherent limitations: sampling error due to the small tissue volume examined (approximately ¹⁄₅₀,000th of total liver mass), inter-observer variability in histological interpretation, procedural complications (including pain in 20–30% and significant bleeding in 0.1–0.5% of patients), and patient reluctance (Dietrich et al., 2017). These limitations have driven the development and adoption of non-invasive assessment methods.

Liver elastography has emerged as the cornerstone of non-invasive liver assessment, fundamentally transforming clinical practice over the past two decades. All elastography techniques share a common scientific foundation: measuring how shear waves propagate through liver tissue. Stiffer tissue, whether from fibrosis, inflammation, or other causes, allows shear waves to travel faster. This simple principle underlies every elastography modality, from FibroScan® to MRI-based techniques.

This article introduces the scientific principles of elastography, explains the biological determinants of liver stiffness, outlines the different technology categories, and discusses the clinical framework for interpretation.

It serves as the foundation for subsequent chapters covering FibroScan® (chapter 3) and ultrasound-based shear wave elastography alternatives (chapter 4).

2.2 The Physics of Liver Elastography

2.2.1 Shear Waves and Tissue Stiffness

All liver elastography techniques measure shear wave velocity, how fast a mechanical wave travels through tissue. Unlike compression waves (which ultrasound imaging uses), shear waves move perpendicular to their direction of propagation, causing tissue to “wiggle” side-to-side as the wave passes.

The critical insight is that shear waves travel faster through stiffer materials. A healthy, soft liver allows shear waves to propagate slowly (approximately 1.0–1.5 m/s). A cirrhotic liver, stiffened by extensive collagen deposition, may see shear waves travel at 2.5–3.0 m/s or faster (Bamber et al., 2013; Barr et al., 2020).

2.2.2 Converting Speed to Stiffness

Shear wave velocity can be converted to tissue elasticity (stiffness) using Young’s modulus equation:

E = 3ρVs²

Where: - E = elasticity, expressed in kilopascals (kPa) - ρ = tissue density (assumed constant at ~1000 kg/m³ for liver) - Vs = shear wave velocity in meters per second (m/s)

This equation shows that elasticity increases with the square of velocity, a small increase in wave speed indicates a larger increase in stiffness. In practice, some devices report results in kPa (after conversion), while others report raw velocity in m/s. Both measure the same underlying property (Ferraioli et al., 2018).

2.2.3 What the Elasticity Numbers Mean

In healthy liver tissue, stiffness typically ranges from 3–7 kPa. As fibrosis progresses, values increase:

Normal liver: 3–7 kPa
Significant fibrosis (F2): ~8–9 kPa
Advanced fibrosis (F3): ~9–12 kPa
Cirrhosis (F4): typically >12–14 kPa, often exceeding 20–25 kPa in advanced cases

These ranges vary by etiology and device, but the principle holds: higher stiffness correlates with more severe fibrosis (Barr et al., 2020).

Importantly, the Baveno VII consensus established that liver stiffness also correlates with hepatic venous pressure gradient (HVPG), enabling non-invasive identification of clinically significant portal hypertension (CSPH). This means elastography is not just a fibrosis staging tool but also a prognostic one (de Franchis et al., 2022).

2.3. The Biological Basis of Liver Stiffness

Liver stiffness correlates strongly, but not perfectly, with fibrosis. Understanding what makes liver tissue stiff is essential for accurate interpretation, because several factors beyond fibrosis influence elastography readings.

2.3.1 Fibrosis: The Primary Determinant

Collagen deposition is the main driver of increased liver stiffness. In chronic liver injury, activated hepatic stellate cells produce excessive extracellular matrix proteins, particularly type I and III collagen. This fibrotic tissue resists deformation, directly increasing shear wave velocity. The correlation between histological fibrosis stage and stiffness is the foundation of elastography’s clinical utility (Schuppan & Afdhal, 2008).

2.3.2 Inflammation

Acute hepatocellular injury raises stiffness independent of fibrosis. During hepatitis flares, hepatocyte swelling and tissue edema transiently stiffen the liver. When alanine aminotransferase (ALT) exceeds 5 times the upper limit of normal, stiffness values may reach cirrhotic ranges even without significant fibrosis. This is why guidelines recommend deferring elastography during acute flares (European Association for the Study of the Liver, 2021; Yoneda et al., 2008).

2.3.3 Cholestasis

Both extrahepatic obstruction (bile duct stones, strictures) and intrahepatic cholestasis (primary biliary cholangitis, drug-induced) elevate stiffness. Increased biliary pressure transmits to surrounding parenchyma. Cholestasis should be excluded before attributing elevated values to fibrosis (Ferraioli et al., 2015).

2.3.4 Hepatic Congestion

Right-sided heart failure, constrictive pericarditis, or elevated central venous pressure causes passive hepatic congestion. The resulting sinusoidal distension stiffens the liver, potentially mimicking cirrhosis in patients with purely cardiac pathology (Tapper & Lok, 2017).

2.3.5 Steatosis

Hepatic fat has a modest, modality-dependent effect on stiffness. While less pronounced than other confounders, severe steatosis may contribute to measurement variability (Younossi et al., 2016).

2.3.6 Post-Prandial State

Eating increases portal blood flow, transiently raising liver stiffness by 10–20%. This effect persists for 2–3 hours, which is why all guidelines require fasting before examination (Mederacke et al., 2009).

Clinical implication: An elevated stiffness value does not automatically indicate fibrosis. The clinical context—including liver enzymes, cardiac status, biliary imaging, and fasting state, must inform interpretation.

2.4. Categories of Elastography Technology

Liver elastography technologies differ in how they generate shear waves, how they track wave propagation, and how they display results. Three main categories exist for liver assessment:

2.4.1 Vibration-Controlled Transient Elastography (VCTE)

VCTE uses an external mechanical vibrator to generate a controlled, low-frequency (50 Hz) shear wave. A dedicated probe placed on the patient’s right intercostal space creates the vibration, while an embedded ultrasound transducer tracks wave velocity along a single line. Results are reported in kPa.

VCTE is embodied commercially by FibroScan® (Echosens, Paris), the first device developed specifically for liver stiffness measurement and the most extensively validated. Importantly, VCTE devices provide no B-mode anatomical imaging, they measure stiffness only (Sandrin et al., 2003; Castera et al., 2005).

FibroScan® technology, probes, CAP measurement, and clinical performance are covered in detail in Chapter 3.

2.4.2 Point Shear Wave Elastography (pSWE)

Also called Acoustic Radiation Force Impulse (ARFI) quantification, pSWE is integrated into conventional ultrasound machines. Instead of mechanical vibration, it uses focused acoustic radiation force to generate a localized shear wave within the liver. Wave velocity is measured at a single point (small region of interest).

The key advantage: pSWE is performed during conventional ultrasound, with B-mode imaging allowing the operator to visualize liver anatomy and select an optimal measurement location (Friedrich-Rust et al., 2009; Nightingale et al., 2002).

2.4.3 Two-Dimensional Shear Wave Elastography (2D-SWE)

2D-SWE represents an evolution of pSWE. Multiple acoustic radiation force “pushes” create shear waves from several focal points in rapid succession. Ultrafast imaging tracks wave propagation across an entire plane, generating a real-time color elasticity map.

This allows visualization of stiffness distribution across a region, with the operator placing a freely-sized ROI within the elastography box. 2D-SWE offers visual confirmation of measurement quality and can assess regional stiffness variations (Herrmann et al., 2018; Dietrich et al., 2017).

pSWE and 2D-SWE technologies, vendors, and comparative performance are covered in Chapter 4.

2.4.4 Magnetic Resonance Elastography (MRE)

It uses a modified MRI technique with an external driver (60 Hz) to image shear wave propagation throughout the entire liver. MRE achieves the highest diagnostic accuracy and is unaffected by obesity, but is limited by cost, availability, and longer examination time. MRE is considered the non-invasive gold standard (Singh et al., 2015). We will cover MRE in chapter 5.

2.5. Key Technical Differences Between Modalities

Understanding how technologies differ explains why their values are not directly interchangeable.

2.5.1 Wave Generation

VCTE: External mechanical vibration (standardized, reproducible)
pSWE/2D-SWE: Acoustic radiation force impulse (deeper targeting, but affected by ultrasound attenuation)

2.5.2 Wave Tracking

VCTE: 1D tracking along a single line
pSWE: Single-point measurement with B-mode guidance
2D-SWE: Plane tracking with ultrafast imaging, producing spatial maps

2.5.3 Sampling Volume

VCTE: Fixed cylindrical volume (~1 cm × 4 cm)
pSWE: Small ROI (5–10 mm)
2D-SWE: Variable ROI within a larger elastography box

2.5.4 Anatomical Imaging

VCTE: None (dedicated stiffness device)
pSWE/2D-SWE: Full B-mode visualization (can avoid vessels, lesions)

2.5.5 Implications for Practice

The 2020 SRU consensus emphasized that values from different manufacturers and modalities are not directly interchangeable. Each uses different shear wave frequencies and measurement algorithms, producing systematic differences. VCTE cut-offs cannot be applied to pSWE results, and vice versa (Barr et al., 2020).

2.6 Universal Acquisition Principles

Regardless of technology, certain principles apply to all elastography examinations. Adherence to these standards is essential for reliable results.

2.6.1 Patient Preparation

Fasting: All guidelines require fasting for at least 2–3 hours. Post-prandial portal hyperemia increases stiffness by 10–20%, potentially causing false-positive results (Mederacke et al., 2009).

Positioning: Supine position with right arm maximally abducted to widen intercostal spaces.

2.6.2 Measurement Location

Right lobe, intercostal approach: Measurements should target the right hepatic lobe through an intercostal window. This avoids: - Compression artifacts from subcostal probe pressure - The left lobe (smaller, more variable, adjacent to heart) - The liver capsule (stiffer than parenchyma)

For techniques with B-mode guidance (pSWE, 2D-SWE), the ROI should be placed at least 1.5–2 cm below the capsule, avoiding large vessels and focal lesions.

2.6.3 Breath-Hold

Quiet, mid-expiratory breath-hold reduces motion artifacts. Deep inspiration compresses the liver against the diaphragm and should be avoided.

2.6.4 Multiple Measurements

No single measurement is sufficient. All techniques require multiple acquisitions to ensure reliability: - The median value is typically reported - Quality metrics (IQR/median ratio, success rate) help identify unreliable examinations - Specific requirements vary by device and are covered in Articles 2 and 3

(Dietrich et al., 2017; Barr et al., 2015)

2.7. Confounders: When Stiffness ≠ Fibrosis

All elastography techniques share the same vulnerability: any factor that stiffens the liver will increase readings, whether or not fibrosis is present.

Confounder	Mechanism	Clinical Action
Acute hepatitis (ALT >5× ULN)	Inflammation and edema	Defer until ALT normalizes
Extrahepatic cholestasis	Biliary obstruction	Exclude before interpreting
Hepatic congestion	Right heart failure, venous congestion	Optimize cardiac status
Recent meal (<2–3 hours)	Post-prandial portal hyperemia	Ensure fasting
Severe steatosis	Mild independent effect	Context-dependent
Ascites	Technical failure (VCTE); variable (SWE)	May preclude examination

(Dietrich et al., 2017; de Franchis et al., 2022)

Rule of thumb: If stiffness is unexpectedly high, ask: Is the patient fasting? Are liver enzymes elevated? Is there cardiac disease or biliary obstruction? Only after excluding confounders should elevated values be attributed to fibrosis.

2.8. Clinical Interpretation Framework

2.8.1 Risk Stratification, Not Staging

Elastography is best used to categorize patients into clinically actionable risk groups rather than to assign precise histological stages. Overlapping stiffness distributions between adjacent fibrosis stages (F1 vs F2, F2 vs F3) mean that a single value cannot reliably distinguish one stage from the next.

Instead, think in terms of:

Low risk: Confidently excludes advanced fibrosis
Indeterminate: Requires additional testing or monitoring
High risk: Indicates likely advanced fibrosis or cirrhosis

The Baveno VII “rule of 5” provides further stratification for patients with compensated advanced chronic liver disease (cACLD): each 5 kPa increment above 10 kPa indicates progressively higher risk of decompensation (de Franchis et al., 2022).

2.8.2 Combine with Laboratory Data

Elastography results should never be interpreted in isolation. Integrate:

AST, ALT: Elevated transaminases suggest inflammation may be contributing
Platelets: Thrombocytopenia supports advanced disease
FIB-4 or NFS: Complementary non-invasive scores

The combination of stiffness with platelet count is particularly powerful. Baveno VII criteria use LSM combined with platelets to rule in or rule out clinically significant portal hypertension without invasive measurement (de Franchis et al., 2022).

2.8.3 Address Discordance

When elastography disagrees with clinical findings or laboratory data: - Consider confounders (inflammation, congestion, non-fasting) - Repeat under optimized conditions - Consider alternative modality (MRE if ultrasound-based results unreliable) - Proceed to biopsy only when histological information will change management

2.8.4 Serial Monitoring

Trends over time are more valuable than single measurements. Elastography’s non-invasive nature allows unlimited serial assessments to track disease progression or response to therapy.

The Baveno VII consensus defines clinically significant improvement as:

≥20% decrease in LSM plus final value <20 kPa, OR
Any decrease resulting in LSM <10 kPa

Such improvements correlate with reduced risk of decompensation and mortality. However, EASL 2021 cautions that decreased stiffness may reflect resolved inflammation rather than true fibrosis regression, interpretation requires clinical context and sustained improvement over time (de Franchis et al., 2022; European Association for the Study of the Liver, 2021).

2.9 Where Elastography Fits in MASLD Care Pathways

Elastography serves different roles depending on clinical setting:

Primary care / Endocrinology: Triage tool to rule out advanced fibrosis and identify patients warranting hepatology referral. EASL recommends a two-tier approach: FIB-4 first, then elastography for those with FIB-4 ≥1.3 (European Association for the Study of the Liver, 2021).

Hepatology clinic: Non-invasive staging without biopsy; annual monitoring for progression or regression; assessing response to lifestyle intervention or pharmacotherapy.

Radiology: Integration of elastography into routine abdominal ultrasound, allowing comprehensive liver assessment in a single examination.

Bariatric medicine: Pre-operative fibrosis assessment and post-operative monitoring of regression.

Clinical trials: Reproducible, non-invasive endpoints for drug development.

2.10. Strengths and Limitations

Strengths

Non-invasive: No pain, bleeding risk, or patient anxiety
Reproducible: Excellent inter- and intra-observer agreement when protocols followed
Prognostic: Predicts clinical outcomes, not just histological stage
Repeatable: Allows unlimited longitudinal monitoring
Reduces biopsy need: Appropriate for most staging and monitoring indications

(Tapper & Lok, 2017; Fraquelli et al., 2007)

Limitations

Affected by non-fibrotic factors: Inflammation, congestion, cholestasis all elevate values
Cannot distinguish cause of stiffness: Fibrosis vs. inflammation vs. congestion
Values not interchangeable: Different devices produce different numbers
Technical failures occur: Obesity, ascites, narrow intercostal spaces
Cannot replace biopsy for all indications: Etiology diagnosis, inflammatory grading, NASH diagnosis require histology

(European Association for the Study of the Liver, 2021)

2.11 Patient Action Checklist: Preparing for Your Liver Elastography Exam

Understanding what liver elastography measures is important, but knowing how to prepare ensures you get the most accurate results. Here’s what you need to do:

Before Your Appointment

Do not eat or drink (except water) for at least 3 hours before your exam. Eating increases blood flow to your liver and can falsely elevate your stiffness reading by 10-20%, potentially suggesting more liver damage than you actually have.

Tell your doctor if you:

Have had a recent hepatitis flare or were told your liver enzymes are significantly elevated (ALT more than 5 times normal)
Have heart failure or have been told you have fluid backing up in your liver
Have gallstones, bile duct problems, or yellowing of your skin/eyes (jaundice)
Have a lot of fluid in your abdomen (ascites)

These conditions can affect your results and may mean your test should be postponed or interpreted with caution.

What to Wear

Wear a shirt or top that allows easy access to your right side between your ribs. You may be asked to raise your right arm above your head during the exam.

During the Exam

Breathe normally when instructed. The technician will ask you to hold your breath briefly and gently during measurements. Avoid deep breaths, they compress the liver and can affect accuracy.

Expect multiple measurements. A single measurement isn’t enough. Your technician will take several readings (typically 10 or more for FibroScan®) to ensure reliability.

The exam is painless. You may feel a slight vibration or “thump” on your skin, but there are no needles, radiation, or discomfort.

After the Exam

Ask about your results in context. A single number doesn’t tell the whole story. Your doctor should interpret your liver stiffness alongside:

Your liver enzyme levels (AST, ALT)
Your platelet count
Other blood tests like FIB-4 score
Your overall health and any other conditions

Request follow-up if needed. If your result is in the “indeterminate” range, additional testing or repeat measurement in a few months may be recommended.

Track your trend over time. If you have chronic liver disease, the change in your stiffness over months or years is often more meaningful than any single measurement.

Questions to Ask Your Doctor

“Was my liver stiffness normal, borderline, or elevated?”
“Could anything other than scarring explain my result?” (inflammation, congestion, recent meal)
“Do I need any follow-up testing?”
“When should I have this test repeated?”
“Based on this result, do I need to see a liver specialist?”

2.12 Summary

Liver elastography measures shear wave velocity as a surrogate for tissue stiffness, which correlates with fibrosis severity and portal pressure. All elastography techniques, VCTE, pSWE, 2D-SWE, and MRE, share this fundamental principle but differ in how waves are generated, tracked, and displayed.

Key points for clinical practice:

Stiffness reflects more than fibrosis: Inflammation, congestion, cholestasis, and meals all increase values
Clinical context is essential: Always interpret alongside ALT, platelets, cardiac status, and fasting state
Think in risk categories: Low / indeterminate / high risk, not precise fibrosis stages
Values are device-specific: Cut-offs from one modality cannot be applied to another
Follow acquisition standards: Fasting, right lobe, intercostal approach, multiple measurements
Use trends for monitoring: Serial measurements track disease trajectory more reliably than single values
Biopsy still has a role: When specific histological information will change management

Understanding these fundamentals enables clinicians to use elastography judiciously, avoid common pitfalls, and integrate results appropriately with clinical and laboratory data.

Next in this series:

Article 2: FibroScan® (VCTE): Principles, Performance, Probes, CAP, and Clinical Use in MASLD
Article 3: Alternatives to FibroScan®: Ultrasound-Based Elastography (pSWE & 2D-SWE)

2.13 References

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