Can Non-Invasive Test Dynamics Serve as Surrogate Endpoints for Histological Improvement in MASH? A Systematic Review and Bayesian Meta-Analysis
In brief
30% drop in liver stiffness doubles odds of fibrosis improvement in MASH trials
A Bayesian meta-analysis of 35 randomized trials found that each 30% reduction in liver stiffness measurement was linked to about a 2.5-fold higher chance of histologic fibrosis improvement, while MRI-derived liver fat showed only moderate correlation with overall disease resolution. The results suggest that non-invasive test changes may reflect response in specific contexts, but they do not yet serve as reliable universal surrogate endpoints.
- Journal
- Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (Q1)
- Published
- 8 September 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Pedro Robson Costa Passos, Valbert Oliveira Costa Filho, Bernardo de Faria Moraes, Igor Boechat Silveira, Leonardo Corrêa Süffert, Guilherme Grossi Lopes Cançado
- PMID
- 42710769
- DOI
- 10.1016/j.cgh.2026.08.030
Why clinicians should know about it
- Picked for Histology (top studies of the week, 13 September 2026): Non‑invasive test dynamics as surrogate endpoints in MASH
- Picked for Biochemistry (medical) (top studies of the week, 13 September 2026): Systematic review of NIT surrogacy for MASH histology
- Picked for Pathology and Forensic Medicine (top studies of the week, 13 September 2026): Non‑invasive test surrogacy for MASH histology
Abstract
BACKGROUND: Trials on metabolic dysfunction-associated steatohepatitis (MASH) use biopsy for efficacy assessment, despite invasiveness and cost. We aimed to assess the trial-level surrogacy and association of changes in non-invasive tests (NITs), namely liver stiffness measurement (LSM), liver fat content (LFC) by magnetic resonance imaging, fibrosis-4 score (FIB-4), and Enhanced Liver Fibrosis (ELF) with histology in MASH. METHODS: We searched PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov up to February 2026 for MASH randomized controlled trials (RCTs) reporting serial NIT data and histological endpoints (fibrosis improvement without MASH worsening or MASH resolution without fibrosis worsening). NIT trial-level surrogacy of histological improvement was quantified through squared Bayesian posterior correlation of treatment effects. RESULTS: Thirty-five RCTs and 3 post-hoc analyses were included. At the trial level, treatment effects on all NITs showed probable weak correlations with histological improvement, with the exception of LFC, which displayed probable moderate surrogacy for MASH resolution without fibrosis worsening (R2 = 62%, 95%CrI 10%-95%). In contrast, variations in LSM were near-certainly associated with fibrosis improvement without MASH worsening in F4-excluded studies (OR 2.67, 95%CrI 1.33-5.12 per 30% decrease) and near-certainly associated with MASH resolution without fibrosis worsening (OR 2.46, 1.16-4.66 per 30% decrease). LFC was near-certainly associated with MASH resolution without fibrosis worsening (OR 1.92, 1.14-3.20 per 30% decrease). CONCLUSION: LFC and LSM dynamics were associated with histological response at the outcome level, but surrogacy was limited and imprecise across biomarkers. This supports a lack of consistent trial-level surrogacy, although context-specific utility remains plausible.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.