Liver and spleen stiffness as assessed by vibration-controlled transient elastography for diagnosing clinically significant portal hypertension in comparison with other elastography-based techniques in adults with chronic liver disease

BACKGROUND: Clinically significant portal hypertension (CSPH) in chronic liver disease (CLD) is a key driver of decompensation, with severe portal hypertension (SPH) leading to severe complications like oesophageal bleeding. Early detection is essential for timely treatment. The current gold standard for assessing portal pressure is hepatic venous pressure gradient (HVPG), an invasive and costly procedure with limited availability. Non-invasive alternatives are increasingly needed to estimate portal pressure (e.g. by liver and spleen stiffness measurement) and guide treatment. However, the diagnostic accuracy of vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), two-dimensional shear wave elastography (2D-SWE), and magnetic resonance elastography (MRE) remains unknown. OBJECTIVES: Primary objectives: to assess the diagnostic accuracy of liver stiffness measurement (LSM) and spleen stiffness measurement (SSM), as well as in combination, measured by any elastography technique (VCTE, pSWE, 2D-SWE, or MRE) in the detection of CSPH in adults with CLD; and to compare the diagnostic accuracies between the individual tests. We will regard a combination of tests as positive when at least one is positive. SECONDARY OBJECTIVES: to assess the diagnostic accuracy of LSM and SSM, as well as in combination, measured by any elastography technique (VCTE, pSWE, 2D-SWE, or MRE) in the detection of SPH in adults with CLD; and to investigate sources of heterogeneity in the results. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Hepato-Biliary Group Diagnostic Test of Accuracy Studies Register, CENTRAL, MEDLINE ALL Ovid, Embase Ovid, LILACS, Science Citation Index - Expanded (Web of Science), and Conference Proceedings Citation Index - Science (Web of Science) until 8 April 2024. We applied no restrictions on language or document type. SELECTION CRITERIA: We included studies that evaluated the diagnostic accuracy of LSM and SSM either alone or in combination, as measured by different elastography techniques (VCTE, pSWE, 2D-SWE, or MRE), for the diagnosis of CSPH and SPH in adults with CLD. We only considered studies with cross-sectional design using HVPG measurement as the reference standard. DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies, extracted data, and assessed the risk of bias and applicability concerns using the QUADAS-C tool. In the case of different cut-off values, we used the hierarchical summary receiver operating characteristic (HSROC) model to meta-analyse data (sensitivities and specificities) and to estimate a summary ROC (SROC) curve. In the case of common cut-off values, we used the bivariate model. We presented uncertainty of the accuracy estimates using 95% confidence intervals (CIs). MAIN RESULTS: We included 47 studies (7817 participants). The most evaluated index test was LSM by VCTE for CSPH (27 studies; 3818 participants). We judged only two studies at low risk of bias for all domains. Most showed high risk in the index test domain due to lack of prespecified thresholds and high concern for applicability in patient selection. Overall, the certainty of evidence was very low. Due to varying thresholds across studies, we used an HSROC model to obtain summary estimates. The main findings for detecting CSPH are below. LSM by VCTE (27 studies, 3818 participants): Sensitivity 72.6% (95% CI 60.0% to 82.5%) at fixed specificity of 90% Specificity 75.9% (95% CI 63.5% to 85.1%) at fixed sensitivity of 90% SSM by VCTE (6 studies, 391 participants): Sensitivity 72.9% (95% CI 27.1% to 95.1%) at fixed specificity of 90% Specificity 80.6% (95% CI 64.1% to 90.7%) at fixed sensitivity of 90% SSM by pSWE (4 studies, 248 participants): Sensitivity 84.1% (95% CI 8.4% to 99.7%) at fixed specificity of 90% Specificity 86.1% (95% CI 40.4% to 98.3%) at fixed sensitivity of 90% LSM by 2D-SWE (10 studies, 767 participants): Sensitivity 73.5% (95% CI 52.6% to 87.4%) at fixed specificity of 90% Specificity 83.4% (95% CI 68.2% to 92.2%) at fixed sensitivity of 80% (estimation at 90% not feasible) SSM by 2D-SWE (6 studies, 353 participants): Sensitivity 80.0% (95% CI 59.8% to 91.5%) at fixed specificity of 90% Estimation at fixed sensitivity not feasible HSROC analysis was not feasible for LSM by pSWE and LSM or SSM by MRE due to insufficient data. For LSM by VCTE at 25 kPa (9 studies, 1553 participants), sensitivity was 62.3% (95% CI 53.0% to 70.7%) and specificity 94.1% (95% CI 87.2% to 97.3%). We explored heterogeneity and observed a prevalence effect: relative specificity 0.90 (95% CI 0.83 to 0.97). Other factors could not be assessed. For SPH as secondary objective, LSM by VCTE was the most evaluated test (8 studies; 637 participants). Sensitivity corresponding to specificity of 90% was 67.2% (95% CI 48.8% to 81.4%), while specificity corresponding to sensitivity of 90% could not be calculated by the HSROC model. Direct comparisons between two index tests were impossible due to inconsistent numbers of participants included for each index test. Due to variability in cut-off values reported across studies, we only performed indirect comparisons using SROC curves. Thus, no reliable results emerged from comparisons or combinations across techniques. AUTHORS' CONCLUSIONS: Liver and spleen stiffness measurements may offer a non-invasive alternative to HVPG for detecting CSPH. However, the accuracy of individual techniques remains uncertain due to very low-certainty evidence and insufficient data for reliable comparisons. No test achieved both sensitivity and specificity ≥ 90%, limiting their utility for confidently ruling in or out CSPH. For LSM by VCTE, the most commonly studied method, HSROC modelling yielded a sensitivity of 72.6% (95% CI 60.0% to 82.5%) at a fixed specificity of 90%, based on studies using various thresholds. In a subgroup of nine studies (1553 participants) using the predefined 25 kPa cut-off, 38% of patients with CSPH would be missed, and 6% without CSPH would be incorrectly identified. The certainty of the evidence is very low, mainly due to high risk of bias, heterogeneity, and imprecision. High-quality research is needed with predefined thresholds, standardised methodology, and improved reporting. Future studies should target key subpopulations (e.g. compensated CLD, specific aetiologies) and assess combinations of non-invasive tools to enhance diagnostic accuracy and clinical usefulness. FUNDING: No internal or external sources of support. REGISTRATION: https://doi.org/10.1002/14651858.CD015415.