The Value of Liver and Spleen Stiffness for Evaluation of Portal Hypertension in Compensated Cirrhosis

Abstract

Patients with compensated advanced chronic liver disease who develop clinically significant portal hypertension (CSPH) are at high risk for hepatic decompensation and mortality if left untreated. Liver biopsy and hepatic venous pressure gradient (HVPG) measurements are the current gold standard procedures for determining fibrosis severity and diagnosing CSPH, respectively; however, both are invasive, limiting their use in clinical practice and larger trials of novel agents. As such, there is an unmet clinical need for reliable, validated, noninvasive measures to detect CSPH and to further assess portal hypertension (PH) severity. Alterations in the biomechanical properties of the liver or spleen in patients with cirrhosis can be quantified by tissue elastography, which examines the elastic behavior of tissue after a force has been applied. A variety of methods are available, including magnetic resonance elastography, shear-wave elastography, and the most thoroughly investigated measure, vibration-controlled transient elastography. Liver stiffness (LS) and spleen stiffness (SS) measurements offer valuable alternatives to detect and monitor CSPH. Both LS and SS correlate well with HVPG, with thresholds of LS >20-25 kPa and SS >40-45 kPa indicating a high likelihood of CSPH. Because SS is a direct and dynamic surrogate of portal pressure, it has the potential to monitor PH severity and assess PH improvement as a surrogate marker for clinical outcomes. Importantly, SS seems to be superior to LS for monitoring treatment response in clinical trials focusing on reducing PH.

FIG. 1

Measurement of HVPG. HVPG is measured by retrograde insertion of a balloon‐tipped central vein catheter into a main hepatic vein. HVPG represents the difference between the occluded hepatic sinusoidal capillary network (wedged hepatic venous) pressure and the free hepatic venous (systemic) pressure. Abbreviations: FHVP, free hepatic venous pressure; IVCP, inferior vena cava pressure; RAP, right atrium pressure; WHVP, wedged hepatic venous pressure.

FIG. 2

Techniques for identifying CSPH. Multiple screening techniques can be used to identify patients at high risk for progression to decompensated cirrhosis, with various cut‐off values to signify the presence of CSPH. Abbreviations: LSM, liver stiffness measurement; SSM, spleen stiffness measurement.