Advances in MASLD and MASH Care Highlight Progress and Persistent Gaps

The rapid rise of metabolic disease has transformed fatty liver disease into one of the most common chronic liver conditions worldwide, forcing clinicians and payers alike to confront gaps in how metabolic dysfunction–associated steatohepatitis (MASH) is identified and treated.1 A comprehensive review published in Annals of Medicine synthesized 2 decades of research advances aimed at improving diagnosis and management of metabolic dysfunction–associated steatotic liver disease (MASLD) and its progressive inflammatory form, MASH.2

Review updates MASH diagnosis and prognosis guidelines, highlighting noninvasive scores, imaging, and emerging therapies, plus lifestyle strategies to improve outcomes. | Image credit: filins - stock.adobe.com

The authors undertook the review in response to the growing clinical and economic burden associated with MASLD, which affects an estimated 25% of the global population and frequently co-occurs with obesity, type 2 diabetes, and metabolic syndrome.1 Progression to MASH increases the risk of fibrosis, cirrhosis, hepatocellular carcinoma, and liver-related mortality, yet diagnosis has historically relied on invasive liver biopsy, and treatment options remain limited.3

“To date, there are no direct serum biomarkers available for diagnosis,” the authors wrote, highlighting a central challenge that has slowed early detection and risk stratification.2

The review detailed how noninvasive diagnostic strategies have expanded substantially, offering alternatives to biopsy for people with suspected MASLD or MASH. These approaches include imaging modalities such as high-resolution CT, MRI, and magnetic resonance elastography, as well as blood-based and composite scoring tools.

Among the most widely used scores are the fibrosis-4 (FIB-4) index and the FibroScan–AST (FAST) score, both designed to identify individuals at risk for advanced fibrosis. The authors also highlighted newer tools, including the Agile 3+ and Agile 4 scores, which demonstrate improved diagnostic performance compared with older indices in people with advanced disease. Enhanced liver fibrosis (ELF) testing, which measures circulating extracellular matrix biomarkers, was noted for its potential utility in population-based screening and cost reduction by limiting unnecessary specialty referrals.

Despite these gains, the authors cautioned that no single modality is sufficient on its own. Inflammatory activity, obesity, and technical variability could influence results, reinforcing the need for multimodal assessment rather than reliance on a single test.

On the therapeutic side, the review underscored significant progress in pharmacologic development, particularly drugs targeting metabolic pathways implicated in hepatic fat accumulation and inflammation. Thyroid hormone receptor β agonists, including resmetirom, have demonstrated histologic improvements in fibrosis and disease resolution in phase 3 trials, while also lowering low-density lipoprotein cholesterol.

Other drug classes discussed included farnesoid X receptor agonists, peroxisome proliferator–activated receptor agonists, sodium-glucose cotransporter 2 inhibitors, and glucagon-like peptide-1 receptor agonists. These agents targeted insulin resistance, lipid metabolism, bile acid signaling, and inflammatory pathways that underpinned disease progression.

However, the authors emphasized that long-term safety and durability of response remained uncertain, noting that many trials were limited in duration and scope. “The feasibility and consistency of these new technologies in large-scale, multicenter clinical practice still need further validation,” they wrote, referring both to diagnostics and therapies.

Lifestyle modification—including dietary change, weight management, and physical activity—was consistently identified as a cornerstone of MASLD and MASH management. The review highlighted evidence supporting Mediterranean-style diets, calorie reduction, and both aerobic and resistance exercise for improving hepatic steatosis and insulin sensitivity.

Behavioral and psychological interventions were also discussed as critical for sustaining lifestyle changes, particularly given the challenges of long-term adherence. For individuals with severe obesity or advanced disease, bariatric surgery showed high rates of MASH resolution and fibrosis improvement, though eligibility and surgical risk limited broader application.

Liver transplantation remains the definitive option for people with end-stage MASH-related liver failure, but donor shortages and posttransplant recurrence pose ongoing challenges.

As a narrative review, the study did not present new patient-level data or pooled outcomes, limiting its ability to draw comparative effectiveness conclusions. Patient demographics varied widely across the studies cited, reflecting global heterogeneity in age, metabolic comorbidities, and disease severity. The authors acknowledged that differences in diagnostic criteria, trial design, and follow-up duration complicated direct comparisons.

The review provided a consolidated framework for understanding how MASLD and MASH care have evolved and where evidence gaps persist.

Looking ahead, the authors called for more personalized approaches and longer-term studies to inform standardized treatment pathways. “Future research should prioritize multidisciplinary collaboration to advance the field of MASLD/MASH,” they concluded, emphasizing the need to align innovation with real-world implementation to improve outcomes for people living with this increasingly prevalent disease.

References

1. Huang DQ, El-Serag HB, Loomba R. Global epidemiology of NAFLD related HCC: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2021;18(4):223-238. doi:10.1038/s41575-020-00381-6
2. Wang D, Miao J, Zhang L, Zhang L. Research advances in the diagnosis and treatment of MASLD/MASH. Ann Med. 2025;57(1):2445780. doi:10.1080/07853890.2024.2445780
3. Younossi ZM, Koenig AB, Abdelatif D, et al. Global epidemiology of nonalcoholic fatty liver disease—meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73-84. doi:10.1002/hep.28431