Performance of ultrasound-guided attenuation parameter and 2D shear wave elastography in patients with metabolic dysfunction-associated steatotic liver disease.

PURPOSE: To assess the performance and the reproducibility of ultrasound-guided attenuation parameter (UGAP) and two-dimensional shear wave elastography (2D-SWE) in patients with biopsy-proven metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: This study included consecutive adult patients with MASLD who underwent ultrasound with UGAP, 2D-SWE and percutaneous liver biopsy. The median values of 12 consecutive UGAP measurements were acquired by two independent radiologists (R1 and R2). Hepatic steatosis was graded by liver biopsy as: (0) < 5%; (1) 5-33%; (2) > 33-66%; (3) > 66%. Areas under the curve (AUCs) were calculated to determine the diagnostic performance. Inter- and intra-observer reliability was assessed with intraclass correlation coefficient (ICC). RESULTS: A hundred patients (median age 55.0 years old) with MASLD were prospectively enrolled. At histopathology, 70 and 42 patients had grade ≥ 2 and 3 steatosis, respectively. Median UGAP was 0.78 dB/cm/MHz (IQR/Med: 5.55%). For the diagnosis of grade ≥ 2 steatosis, the AUCs of UGAP were 0.828 (95% CI: 0.739, 0.896) for R1 and 0.779 (95% CI: 0.685, 0.856) for R2. The inter- and intra-operator reliability of UGAP were excellent, with an ICC of 0.92 (95% CI: 0.87-0.95) and 0.95 (95% CI: 0.92-0.96), respectively. The median liver stiffness was 6.76 kPa (IQR/Med: 16.30%). For the diagnosis of advanced fibrosis, 2D-SWE had an AUC of 0.862 (95% CI: 0.757, 0.934), and the optimal cutoff value was > 6.75 kPa with a sensitivity of 80.6% and a specificity of 75.7%. CONCLUSION: UGAP and 2D-SWE provide a good performance for the staging of steatosis and fibrosis in patients with MASLD with an excellent intra-operator reliability of UGAP. KEY POINTS: Question How well do ultrasound-guided attenuation parameter (UGAP) and two-dimensional shear wave elastography (2D-SWE) perform for quantifying hepatic steatosis and fibrosis? Findings UGAP had a maximum AUC of 0.828 for the diagnosis of grade ≥ 2 steatosis, and 2D-SWE had an AUC of 0.862 for diagnosing advanced fibrosis. Clinical relevance UGAP and 2D-SWE allow rapid, reproducible, and accurate quantification of hepatic steatosis and fibrosis that can be used for the noninvasive assessment of patients with metabolic dysfunction-associated steatotic liver disease.

Clinical outcomes of MAFLD versus NAFLD: A meta-analysis of observational studies.

IMPORTANCE: The recent change in terminology from nonalcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) highlights the link between hepatic steatosis and metabolic dysfunction, taking out the stigmata of alcohol. OBJECTIVE: We compared the effects of NAFLD and MAFLD definitions on the risk of overall and cardiovascular (CV) mortality, liver-related events (LRE), nonfatal CV events (CVE), chronic kidney disease (CKD), and extra-hepatic cancers (EHC). DATA SOURCES AND STUDY SELECTION: We systematically searched four large electronic databases for cohort studies (published through August 2023) that simultaneously used NAFLD and MAFLD definitions for examining the risk of mortality and adverse CV, renal, or oncological outcomes associated with both definitions. In total, 21 eligible cohort studies were identified. Meta-analysis was performed using random-effects modelling. RESULTS: Compared with those with NAFLD, individuals with MAFLD had significantly higher rates of overall mortality (random-effect OR 1.12, 95% CI 1.04-1.21, p = .004) and CV mortality (random-effect OR 1.15, 95% CI 1.04-1.26, p = .004), and a marginal trend towards higher rates of developing CKD (random-effect OR 1.06, 95% CI 1.00-1.12, p = .058) and EHC events (random-effect OR 1.11, 95% CI 1.00-1.23, p = .052). We found no significant differences in the risk LREs and nonfatal CVE between MAFLD and NAFLD. Meta-regression analyses identified male sex and metabolic comorbidities as the strongest risk factors related to the risk of adverse clinical outcomes in MAFLD compared to NAFLD. CONCLUSIONS AND RELEVANCE: Individuals with MAFLD have higher rates of overall and CV mortality and higher rates of developing CKD and EHC events than those with NAFLD, possibly due to the dysmetabolic risk profile related to MAFLD.

Are we ready for genetic testing in metabolic dysfunction-associated steatotic liver disease?

Metabolic dysfunction-associated steatotic liver disease (MASLD), with its steadily increasing prevalence, represents now a major problem in public health. A proper referral could benefit from tools allowing more precise risk stratification. To this end, in recent decades, several genetic variants that may help predict and refine the risk of development and progression of MASLD have been investigated. In this review, we aim to discuss the role genetics in MASLD plays in everyday clinical practice. We performed a comprehensive literature search of PubMed for relevant publications. Available evidence highlights the emergence of genetic-based noninvasive algorithms for diagnosing fatty liver, metabolic dysfunction-associated steatohepatitis, fibrosis progression and occurrence of liver-related outcomes including hepatocellular carcinoma. Nevertheless, their accuracy is not optimal and application in everyday clinical practice remains challenging. Furthermore, susceptible genetic markers have recently become subjects of great scientific interest as therapeutic targets in precision medicine. In conclusion, decisional algorithms based on genetic testing in MASLD to facilitate the clinician decisions on management and treatment are under growing investigation and could benefit from artificial intelligence methodology.

MAFLD: a multisystem disease.

Nonalcoholic fatty liver disease (NAFLD), affecting about 25% of general population and more than 50% of dysmetabolic patients, is an emerging cause of chronic liver disease and its complications. Recently, an international consensus of experts proposed to rename this disease as 'Metabolic dysfunction-Associated Fatty Liver Disease' (MAFLD) to focus on the bidirectional interplay between fatty liver and metabolic alterations and to stress the need of assessing fatty liver independently from alcohol consumption and other coexisting causes of liver disease. The peculiarity of NAFLD/MAFLD lies in the presence of a higher risk of not only - as expected - liver-related events but also of extrahepatic events, mostly cardiovascular and cancers. Available evidence suggests that these associations are not only the expression of sharing the same risk factors but shed light about the ability of NAFLD/MAFLD and particularly of its progressive form - nonalcoholic/metabolic dysfunction-associated steatohepatitis - to act as an independent risk factor via promotion of atherogenic dyslipidemia and a proinflammatory, profibrogenic, and procoagulant systemic environment. The present review summarizes available epidemiological and clinical evidence supporting the concept of NAFLD/MAFLD as a multisystemic disease, and highlights potential explanatory mechanisms underlying the association between NAFLD/MAFLD and extrahepatic disorders.

AGILE 3+ Score for the Diagnosis of Advanced Fibrosis and for Predicting Liver-related Events in NAFLD.

BACKGROUND & AIMS: We aimed to assess the diagnostic accuracy of AGILE 3+, a recently developed score based on the combination of aspartate aminotransferase/alanine aminotransferase ratio, platelet count, diabetes status, sex, age, and liver stiffness measurement (LSM) by transient elastography, when compared with Fibrosis-4 (FIB-4) and LSM, for the diagnosis of advanced fibrosis and for the prediction of liver-related events (LREs) occurrence in patients with NAFLD. METHODS: A total of 614 consecutive patients with biopsy-proven NAFLD or clinical diagnosis of NAFLD-related compensated cirrhosis were enrolled. LREs were recorded during follow-up. FIB-4, LSM by transient elastography (FibroScan device), and AGILE 3+ were measured. The diagnostic performance of noninvasive criteria for advanced fibrosis and for the prediction of LREs was assessed using the area under the receiver operating characteristic curve (AUROC) and decision curve analysis. RESULTS: In patients with biopsy-proven NAFLD (n = 520), LSM and AGILE 3+ had higher AUROC than FIB-4 (0.88 for LSM and AGILE 3+ vs 0.78 for FIB-4; P < .001) for advanced fibrosis, and AGILE 3+ exhibited a smaller indeterminate area in the test (25.2% for FIB-4 vs 13.1% for LSM vs 8.3% for AGILE 3+). Within the entire cohort of patients, AGILE 3+ had significantly higher AUROC for predicting LREs with respect to LSM (AUROC 36 months 0.95 vs 0.93; P =.008; 60 months 0.95 vs 0.92; P = .006; 96 months 0.97 vs 0.95; P = .001). Decision curve analysis showed that all scores had modest net benefit for ruling-out advanced fibrosis at the risk threshold of 5% to 10% where advanced fibrosis was absent. At the risk threshold of 5% of false negatives or false positives in LRE at 36, 60, 96, and 120 months, AGILE 3+ outperformed both FIB-4 and LSM for ruling out LRE. CONCLUSIONS: Depending on resource availability, clinical setting, and the risk scenarios, AGILE 3+ is an accurate and valid alternative to FIB-4 and LSM for the noninvasive assessment of disease severity and prognosis in patients with NAFLD.

Non-intrusive PODI-ROM for patient-specific aortic blood flow in presence of a LVAD device.

Left ventricular assist devices (LVADs) are used to provide haemodynamic support to patients with critical cardiac failure. Severe complications can occur because of the modifications of the blood flow in the aortic region. In this work, the effect of a continuous flow LVAD device on the aortic flow is investigated by means of a non-intrusive reduced order model (ROM) built using the proper orthogonal decomposition with interpolation (PODI) method based on radial basis functions (RBF). The full order model (FOM) is represented by the incompressible Navier-Stokes equations discretized by using a Finite Volume (FV) technique, coupled with three-element Windkessel models to enforce outlet boundary conditions in a multi-scale approach. A patient-specific framework is proposed: a personalized geometry reconstructed from Computed Tomography (CT) images is used and the individualization of the coefficients of the three-element Windkessel models is based on experimental data provided by the Right Heart Catheterization (RHC) and Echocardiography (ECHO) tests. At FOM level, we also consider the pre-surgery configuration in order to further validate the predictive capabilities of the model in several contexts. The ROM has been tested by considering a parametric setting with respect to the LVAD flow, which is a crucial parameter of the problem. We consider a parameter range that covers typical clinical values. The accuracy of the ROM is assessed against results obtained with the FOM both for primal, velocity and pressure, and derived quantities, wall shear stress (WSS). Finally, we briefly discuss the efficiency of our ROM approach.