Wu, Hao

Background: Accurate identification of patients with metabolic dysfunction–associated steatohepatitis (MASH) at risk of disease progression (at-risk MASH) is critical for guiding resmetirom and semaglutide therapy. Inconsistent definitions of at-risk MASH complicate clinical risk classification and comparisons across studies. This study aimed to standardize the definition of at-risk MASH and propose optimized MRE-based liver stiffness (LS-MRE) cutoffs to improve noninvasive risk stratification and better guide pharmacotherapy. Methods: In this prospective study, 413 patients with suspected or diagnosed MASLD from two medical centers underwent liver biopsy and MRE. Results: A simplified definition of at-risk MASH (MASH with fibrosis stage≥2) identified a broader group of patients requiring clinical attention than a stricter definition requiring NAFLD Activity Score≥4 with ≥1 point in steatosis, inflammation, and ballooning (n=122 vs. 77). LS-MRE alone showed the highest diagnostic accuracy for identifying at-risk MASH using the simplified definition (AUC 0.91 [0.87, 0.95]) and cirrhosis (AUC 0.93 [0.88, 0.99]), compared with FIB-4 and individual laboratory parameters (AST, ALT, and platelet count) ( p <0.01 for all, paired DeLong tests). Optimized LS-MRE cutoffs (2.8–6.4 kPa) captured 25 additional biopsy-proven pharmacotherapy candidates (28% of all eligible patients) compared to AASLD guidelines–recommended cutoffs (3.1–4.4 kPa), improving sensitivity (80% vs. 50%) with acceptable specificity (73% vs. 88%). Conclusions: A simplified definition of at-risk MASH enables broader identification of treatment candidates. LS-MRE demonstrates excellent diagnostic performance and improves noninvasive risk stratification when paired with optimized cutoffs. These findings support the use of MRE to guide resmetirom and semaglutide eligibility and improve access to emerging therapies.

Background: Qualification of non-invasive tests (NITs) and blood biomarkers for fibrosis severity and risk assessment is an unmet need in clinical care for cirrhosis. The paucity of reproducibility data for imaging and blood biomarkers in cirrhosis hinders their application for longitudinal monitoring. The aim of this study was to evaluate the reproducibility of imaging and blood biomarkers in a prospective cohort of adults with cirrhosis. Methods: We prospectively enrolled adults with cirrhosis in an observational, longitudinal cohort study. Participants completed a research visit with vibration-controlled transient elastography (VCTE) with liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) and blood testing, including AST, ALT, platelets, alpha-fetoprotein (AFP), and the Fibrosis-4 Index (FIB-4). Biomarkers were repeated a median of 3 months apart without any interim intervention. The primary outcome was the reproducibility of each biomarker as assessed by the reproducibility coefficient (RDC%), within-participant coefficient of variation (wCV), intraclass correlation coefficient (ICC), and Bland–Altman analysis. Results: In total, 40 participants (mean age 62, 60% female, mean BMI 28.6 kg/m 2 ) had VCTE/CAP, 38 AST/ALT, and 26 had AFP at both time points. The RDC% for VCTE-LSM was 54.4, wCV 0.19, and ICC 0.91. VCTE CAP had an RDC% of 56, a wCV of 0.30, and ICC 0.47. AFP had an RDC% of 58, a wCV of 0.21, and an ICC of 0.95. RDC% for AST, ALT, and FIB-4 ranged from 70% to 79%. On Bland–Altman analyses, VCTE-LSM demonstrated the lowest relative bias (0.4%). Conclusions: Prospective assessment of repeat biomarkers in adults with cirrhosis found that VCTE-LSM and CAP provide consistent assessments across individuals but may yield substantial within-individual variation. Blood-based biomarkers had poor reproducibility within individuals but were consistent in detecting between-patient variability. These data can inform ultrasound-based non-invasive testing qualification by defining thresholds that may reflect measurement variability rather than true biologic change over time.

Spatial heterogeneity of liver viscoelasticity, measured at three-dimensional vector MR elastography, positively correlated with metabolic dysfunction–associated steatotic liver disease progression.

BackgroundMR elastography (MRE) at 60 Hz is widely used for staging liver fibrosis. MRE with lower frequencies may provide inflammation biomarkers.PurposeTo establish a practical simultaneous dual‐frequency liver MRE protocol at both 30 Hz and 60 Hz during a single examination and validate the occurrence of second harmonic waves at 30 Hz.Study TypeRetrospective.SubjectsOne hundred six patients (48 females, age: 50.0 ± 13.4 years) were divided as follows: Cohort One (15 patients with chronic liver disease [CLD] and 25 healthy volunteers) with simultaneous dual‐frequency MRE. Cohort Two (66 patients with CLD) with second harmonic MRE.Field Strength/Sequence3‐T, single‐ or dual‐frequency MRE at 30 Hz and 60 Hz.AssessmentLiver stiffness (LS) in both cohorts was evaluated with manually placed volumetric ROIs by two independent analyzers. Image quality was assessed by three independent readers on a 4‐point scale (0–3: none/failed, fair, moderate, excellent) based on the depth of wave propagation with 1/3 incremental penetration. The success rate was derived from the percentage of nonzero quality scores.Statistical TestsMeasurement agreement, bias, and repeatability of LS were assessed using intraclass correlation coefficients (ICCs), Bland–Altman plots, and repeatability coefficient (RC). Mann–Whitney U tests were used to evaluate the differences in image quality between different methods. A P‐value <0.05 was considered statistically significant.ResultsSuccess rate was 97.5% in Cohort One and 91% success rate for the second harmonic MRE in Cohort Two. The second harmonic and conventional MRE showed excellent agreement in LS (all ICCs >0.90). The quality scores for the second harmonic wave images were lower than those from the conventional MRE (Z = −4.523).Data ConclusionCompared with conventional and second harmonic methods, simultaneous dual‐frequency had better image quality, high success rate and the advantage of intrinsic co‐registration, while the second harmonic method can be an alternative if custom waveform is not available.Evidence Level3Technical EfficacyStage 1