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Background & Aims: A noteworthy proportion of patients with metabolic dysfunction-associated steatotic liver disease (MASLD) have an indeterminate vibration-controlled transient elastography (VCTE). Among these patients, we aimed to identify candidates for MASLD treatment by diagnosing significant fibrosis., Methods: Real-world prospective study including a large dataset of MASLD patients with paired VCTE and liver biopsy from 6 centers. A total of n=1196 patients were recruited and divided in training (3 centers, Spain), internal validation (2 centers, Spain), and external validation (1 center, United States) cohorts. In patients with indeterminate liver stiffness measurements (LSM:8-12 kPa), a diagnostic algorithm was developed to identify significant fibrosis, defined as histological stage ≥F2. Statistical analysis was performed using gaussian mixture model (GMM) and k-means unsupervised clusterization., Results: From the eligible population, 33%, 29%, and 31% had indeterminate VCTE in the training, internal and external validation samples, respectively. Controlled attenuation parameter (CAP) allowed the differentiation of GMM clusters with a cut-off of 280 dB/m (AUC:0.89 [95%CI:0.86-0.97]). Within patients with <280 dB/m, a LSM between 8.0-9.0 kPa showed a 93% sensitivity and a 91% negative predictive value to exclude significant fibrosis. Among patients with ≥280 dB/m, a LSM between 10.3-12.0 kPa diagnosed significant fibrosis with a 91% specificity. Applying this algorithm to the validation cohorts, 36% of the indeterminate VCTE were re-allocated. The re-allocated high-risk group showed a prevalence of 86% significant fibrosis, opening the therapeutic window for MASLD patients., Conclusion: To identify candidates for MASLD treatment among indeterminate VCTE, an algorithm-based on the sequential combination of LSM and CAP thresholds can optimize the diagnosis of moderate-to-advanced fibrosis., (Copyright © 2024. Published by Elsevier Inc.)

Purpose:  Peripheral responses might be important in handcycling, given the involvement of small muscles compared to other exercise modalities. Therefore, the goal of this study was to compare changes in muscle oxygen saturation (∆SmO 2 ) and deoxyhemoglobin level (∆[HHb]) between different efforts and muscles., Methods:  Handcyclists participated in a Wingate, a maximal incremental test and a 20-min time-trial (TT). Oxygen uptake (VO 2 ) as well as ∆SmO 2 , ∆[HHb], deoxygenation and reoxygenation rates in the triceps brachii (TB), biceps brachii (BB), anterior deltoid (AD) and extensor carpi radialis brevis (ER) were measured., Results:  ER ∆[HHb]max was 37% greater in the incremental test than in the Wingate (ES = 0.392, P = 0.031). TT mean power (W/kg) was associated with BB ∆SmO 2 min measured in the incremental test (r = -0.998 [-1.190, -0.806], P = 0.002) and in the Wingate (r = -0.994 [-1.327, -0.661], P = 0.006). MAP (W/kg) was associated with Wingate BB ∆SmO 2 min (r = -0.983 [-0.999, -0.839], P = 0.003), and Wingate peak (r = 0.649 [0.379, 0.895], P = 0.008) and mean power (W/kg) (r = 0.925 [0.752, 0.972], P = 0.003) was associated with right handgrip force. The strongest physiological predictor for TT performance was BB ∆SmO 2 min in the incremental test (P = 0.002, r 2  = 0.993, SEE 0.016 W/kg), Wingate BB ∆SmO 2 min for MAP (P = 0.003, r 2  = 0.956, SEE 0.058 W/kg) and right handgrip force for Wingate peak power (P = 0.005, r 2  = 0.856, SEE 0.551 W/kg)., Conclusion:  Peripheral aerobic responses (muscle oxygenation) were predictive of handcycling performance., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Aims: Diagnosis of metabolic dysfunction-associated steatohepatitis (MASH) requires histology. In this study, a magnetic resonance imaging (MRI) score was developed and validated to identify MASH in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Secondarily, a screening strategy for MASH diagnosis was investigated., Methods: This prospective multicentre study included 317 patients with biopsy-proven MASLD and contemporaneous MRI. The discovery cohort (Spain, Portugal) included 194 patients. NAFLD activity score (NAS) and fibrosis were assessed with the NASH-CRN histologic system. MASH was defined by the presence of steatosis, lobular inflammation, and ballooning, with NAS ≥4 with or without fibrosis. An MRI-based composite biomarker of Proton Density Fat Fraction and waist circumference (MR-MASH score) was developed. Findings were afterwards validated in an independent cohort (United States, Spain) with different MRI protocols., Results: In the derivation cohort, 51% (n = 99) had MASH. The MR-MASH score identified MASH with an AUC = .88 (95% CI .83-.93) and strongly correlated with NAS (r = .69). The MRI score lower cut-off corresponded to 88% sensitivity with 86% NPV, while the upper cut-off corresponded to 92% specificity with 87% PPV. MR-MASH was validated with an AUC = .86 (95% CI .77-.92), 91% sensitivity (lower cut-off) and 87% specificity (upper cut-off). A two-step screening strategy with sequential MR-MASH examination performed in patients with indeterminate-high FIB-4 or transient elastography showed an 83-84% PPV to identify MASH. The AUC of MR-MASH was significantly higher than that of the FAST score (p < .001)., Conclusions: The MR-MASH score has clinical utility in the identification and management of patients with MASH at risk of progression., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)