A new framework for diagnosis
The 2024 European clinical practice guidelines introduce a pivotal terminology shift, replacing NAFLD (non-alcoholic fatty liver disease) with MASLD (metabolic dysfunction-associated steatotic liver disease) and NASH with MASH (metabolic dysfunction-associated steatohepatitis). This renaming is not just semantic—it provides a pathophysiologically grounded, inclusive classification system based on the presence of hepatic steatosis and at least one cardiometabolic risk factor.
Importantly, MASLD is now grouped under the umbrella of "steatotic liver disease" (SLD), along with alcohol-associated liver disease (ALD), cryptogenic steatosis, and other causes. A new subcategory—MetALD (MASLD with moderate alcohol use)—acknowledges mixed etiologies seen in clinical practice. Individuals with MetALD have distinct clinical profiles and are at heightened risk for cardiovascular and liver-related complications.
Risk factors and pathogenesis
The guidelines stress the tight link between MASLD and metabolic disorders such as obesity, type 2 diabetes (T2D), dyslipidaemia, and hypertension. Genetic predispositions (e.g., PNPLA3, TM6SF2), age, male sex, postmenopausal status, polycystic ovary syndrome, and obstructive sleep apnoea also elevate risk for disease progression to MASH and fibrosis.
MetALD is highlighted as an especially high-risk subgroup. Even moderate alcohol consumption synergistically worsens hepatic injury in the context of metabolic dysfunction. Guidelines now discourage any alcohol intake in patients with MASLD and recommend validated tools or biomarkers for more accurate alcohol use assessment.
Screening and monitoring: a targeted, non-invasive approach
Routine screening for MASLD in the general population is not recommended due to cost and low yield. Instead, the focus is on high-risk groups: individuals with T2D, central obesity with another cardiometabolic risk factor, or persistently elevated liver enzymes. A stepwise algorithm using the fibrosis-4 (FIB-4) index is advocated. For intermediate-risk individuals, two strategies are offered: (A) second-line imaging such as transient elastography, or (B) intensified cardiometabolic management with repeat testing in 12 months. This flexible framework considers resource availability and clinical urgency. Non-invasive tests (NITs)—both serum biomarkers and imaging-based tools—are preferred for fibrosis staging, monitoring treatment response, and prognostication. Liver biopsy is now reserved for select cases with diagnostic uncertainty.
Lifestyle interventions: still the cornerstone
Despite pharmacological advances, lifestyle modification remains the backbone of MASLD management. The guidelines recommend a weight loss of ≥5% for reducing steatosis, 5–10% to reduce inflammation, and ≥10% to reverse fibrosis. Normal-weight individuals can also benefit from modest (3–5%) weight loss due to underlying metabolic derangements.
The Mediterranean diet—rich in vegetables, legumes, fish, nuts, and olive oil—is the dietary model of choice. Ultra-processed foods, sugar-sweetened beverages, and alcohol should be minimized. At least 150 minutes of moderate or 75 minutes of vigorous physical activity per week is advised, with a focus on sustainability and access to multidisciplinary support.
Pharmacological options: emerging but promising
Several pharmacologic agents—initially developed for diabetes and obesity—have shown promise in MASLD: (i) Incretin mimetics such as semaglutide and tirzepatide are the most validated. (ii) SGLT2 inhibitors, metformin, and statins, while lacking histologic trial endpoints, improve liver enzymes, reduce hepatic fat, and lower cardiovascular risk. (iii) Resmetirom, a thyroid hormone receptor β-agonist, received accelerated FDA approval for non-cirrhotic MASH with stage F2 fibrosis or greater, based on the MAESTRO-NASH trial. These developments suggest a dynamic therapeutic landscape is emerging, moving MASLD management closer to targeted, individualized therapy.
Bariatric surgery and end-stage disease
Bariatric/metabolic surgery remains the most effective long-term intervention for patients with severe obesity and MASLD. Trials demonstrate that procedures like gastric sleeve or Roux-en-Y bypass resolve MASH and improve fibrosis in many cases. Surgery also reduces major cardiovascular and hepatic outcomes. For patients with compensated cirrhosis, surgery should only be considered at experienced centres following comprehensive risk assessment. Endoscopic weight-loss procedures are still investigational in this context. At the end-stage spectrum, liver transplantation remains the definitive therapy for patients with decompensated cirrhosis or hepatocellular carcinoma (HCC). Careful cardiometabolic assessment is essential to optimize outcomes post-transplant. Nutritional guidance to prevent sarcopenia and hepatic decompensation is also crucial in patients undergoing moderate weight loss.
Looking ahead: integration and prevention
The new guidelines underscore the need for integrated care. Effective MASLD management spans hepatology, endocrinology, nutrition, primary care, and public health. Prevention strategies—targeting obesity, food policy, and health literacy—remain vital at the population level. The authors call for broader implementation of multidisciplinary programs and continued research into novel diagnostics, therapeutics, and care delivery models.
See the article:
Horn P, Tacke F. Key takeaways from the updated multidisciplinary European MASLD guidelines. eGastroenterology 2025;3:e100196. doi:10.1136/ egastro-2025-100196
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