Letter: Advancing Non-Invasive Assessment Tools for MASLD—A Focus on Disease Remission

We read with interest the article by Noureddin et al. on the use of non-invasive tests (NITs) to monitor patients with metabolic dysfunction-associated steatotic liver disease (MASLD) [1]. While liver biopsy remains the gold standard for assessing MASLD severity, its invasive nature, high cost, procedural risks (e.g., bleeding, sampling variability) and patient discomfort limit its utility for repeated testing. Consequently, there is an urgent need for safe, cost-effective and reliable non-invasive tools to screen, stage and prognosticate MASLD. The review by Noureddin et al. addresses this gap by evaluating existing NITs and proposing stage-specific monitoring protocols.

However, while the review thoroughly examines disease progression, the assessment of disease remission is equally important. Recent studies, particularly a study by Feng et al., have expanded our understanding of MASLD's natural history, emphasising the reversibility of fibrosis, fluctuations in inflammation and steatosis and even recompensation in patients with decompensated cirrhosis [2, 3]. These findings underscore the importance of developing tools that can assess not only disease progression but also remission. The approval of resmetirom—the first drug for metabolic dysfunction-associated steatohepatitis (MASH) with significant fibrosis—has accelerated demand for non-invasive remission assessment tools [4]. Replacing liver biopsy with validated, non-invasive methods to assess the histological resolution of MASLD is a critical frontier in MASLD research [4-6].

Recent research on histological remission and related NITs has begun to shed light on this essential aspect of MASLD management. For instance, Raverdy et al. evaluated NITs for fibrosis monitoring post-bariatric surgery, and Loomba et al. developed the MASH Histological Remission Index [5, 7]. Furthermore, Loomba et al. also identified associations between baseline metabolic markers (e.g., triglycerides, alanine aminotransferase changes) and histological outcomes [8]. However, critical gaps persist. Most studies focus narrowly on fibrosis improvement or MASH remission, with limited data on their long-term impact on liver-related outcomes. Few have examined the synergistic effects of combined fibrosis reversal and MASH remission, and existing tools lack validation across diverse populations (e.g., varying demographics, comorbidities), raising concerns about generalisability. Large-scale, multicentre, longitudinal studies are essential to address these limitations [5, 7]. To advance non-invasive tools for MASLD remission, a multipronged approach is necessary for (1) optimising existing methods by refining protocols, thresholds and multimodal integration; (2) identifying novel biomarkers through mechanistic research at genetic and metabolic levels; (3) validating tools across diverse populations and disease stages and (4) establishing standardised guidelines to ensure consistency in clinical application and interpretation.

In summary, Noureddin et al.'s review offers a timely synthesis of NITs for MASLD progression. Moving forward, efforts must prioritise enhancing test accuracy, accessibility and applicability across patient subgroups. Equally important is expanding the role of NITs to evaluate disease remission—a step that could transform MASLD management, improve patient outcomes and alleviate the global burden of this condition.

Gong Feng: writing – review and editing, writing – original draft, supervision, resources, conceptualization. Na He: writing – original draft, writing – review and editing, validation. Hui Wang: writing – original draft. Yi Liu: writing – original draft, writing – review and editing, conceptualization, supervision.

The authors declare no conflicts of interest.

This article is linked to Noureddin et al paper. To view this article, visit https://doi.org/10.1111/apt.17752.