Ultrasound Elastography: A Non-Invasive Approach to Assess Liver Fibrosis in NAFLD Patients

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Liver fibrosis, a key determinant of prognosis and mortality, plays a pivotal role in predicting hepatic and extrahepatic events in patients with Non-Alcoholic Fatty Liver Disease (NAFLD). The risk of severe liver disease escalates with the increasing stage of fibrosis, leading to distinct outcomes for patients with cirrhosis or bridging fibrosis. NAFLD patients with cirrhosis are prone to liver-related events, while those with bridging fibrosis face a higher likelihood of non-hepatic cancers and vascular events.

Despite the significance of fibrosis staging, liver biopsy remains the gold standard for determining the severity of fibrosis. The histological classification involves five stages (F0–F4). However, liver biopsy poses several drawbacks, necessitating the exploration of non-invasive alternatives for assessing liver fibrosis in NAFLD patients.

Traditional imaging examinations, particularly sonography of the liver, have been foundational in the initial assessment of advanced chronic liver diseases. While certain characteristic changes in the liver, such as a nodular surface and inhomogeneous parenchyma, exhibit high specificity for cirrhosis diagnosis, their sensitivity is limited. The quest for more accurate and non-invasive methods led to the development of ultrasound elastography.

Ultrasound elastography comprises various non-invasive techniques, each employing distinct physical approaches. Notable methods include Transient Elastography (TE), utilizing a mechanical external push; Acoustic Radiation Force Impulse (ARFI) techniques, involving an acoustic internal push; and Strain Elastography (SE), based on tissue deformation caused by external pressure or internal physiological movements like breathing and heartbeat.

The groundbreaking FibroScan from Echosens, introduced in 2002, measures the speed of shear waves generated by a mechanical impulse transmitted through the liver tissue. Shear waves, which move perpendicular to their direction of propagation, display different speeds in soft and hard tissues. The speed of shear waves correlates with liver stiffness, which, in turn, reflects the degree of fibrosis. TE has proven effective in determining fibrosis severity in various chronic liver diseases.

Evolving Techniques: From TE to 2D-Shear Wave Elastography

As ultrasound technology advanced, manufacturers incorporated elastography functions into their devices, introducing point shear wave elastography (pSWE) and 2D-Shear Wave Elastography (2D-SWE). Unlike TE, these techniques generate shear waves through an acoustic radiation force impulse (ARFI).

In 2D-SWE, a defined region of interest (ROI) is selected within the liver parenchyma, and the shear wave velocity is measured, allowing for the conversion of values to kilopascals (kPa). While both TE and 2D-SWE employ shear wave velocity as a measure of tissue stiffness, applying cut-off values from TE to 2D-SWE poses a significant challenge due to variations in calculation methods among manufacturers.

A meta-analysis of studies on NAFLD patients revealed the diagnostic accuracy of TE, pSWE, and 2D-SWE for detecting significant fibrosis (≥F2), advanced fibrosis (≥F3), and cirrhosis (F4). TE demonstrated good accuracy, while pSWE and 2D-SWE showed varying degrees of sensitivity and specificity across fibrosis stages.

Despite the promise of ultrasound elastography, challenges persist. Technical failures, especially in obese patients, are common, and the availability of elastography methods can be limited in certain regions. Moreover, the lack of standardized cut-off values and variations in reference values among manufacturers complicate the interpretation of results.

Strain elastography, although studied, has limited utility compared to shear wave elastography. While some studies suggest its reliability for identifying early-stage fibrosis, it generally lags behind shear wave elastography in diagnostic accuracy, as demonstrated by comparative meta-analyses.

In the quest for improved diagnostic accuracy, some authors propose "combinational elastography," combining strain and shear wave imaging to enhance the relevance of each technique. Ongoing studies aim to refine shear-wave speed measurements and define minimum clinically detectable differences in liver stiffness, facilitating longitudinal monitoring of patients with Chronic Liver Disease (CLD).

In summary, ultrasound elastography signifies a notable progression in non-invasive liver fibrosis assessment for NAFLD patients, offering the potential to transform the diagnosis and monitoring of liver fibrosis with more precise and patient-focused methods in chronic liver diseases.