EASL–EASD–EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD)

Tacke, Frank; Horn, Paul; Wai-Sun Wong, Vincent; Ratziu, Vlad; Bugianesi, Elisabetta; Francque, Sven; Zelber-Sagi, Shira; Valenti, Luca; Roden, Michael; Schick, Fritz; Yki-Järvinen, Hannele; Gastaldelli, Amalia; Vettor, Roberto; Frühbeck, Gema; Dicker, Dror

doi:10.1016/j.jhep.2024.04.031

Cited by 113 publications

(2 citation statements)

References 515 publications

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“…Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease, involves the presence of hepatic steatosis in combination with a cardiometabolic risk factor [1]. MASLD covers isolated hepatic steatosis, metabolic dysfunction-associated steatohepatitis (MASH), different degrees of liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC) [2]. Hence, this new definition highlights the metabolic roots of the disease and its association with obesity, type 2 diabetes mellitus (T2DM) and other cardiometabolic risk factors [1,3].…”

Section: Introductionmentioning

confidence: 99%

“…The pathophysiology behind MASLD is complex, primarily driven by insulin resistance, leading to increased hepatic uptake of fatty acids and their accumulation in the liver [4,5]. Additionally, oxidative stress and chronic low-grade inflammation exacerbate liver damage, promoting progression from simple steatosis to more severe liver conditions [2]. This progression is often amplified by genetic predispositions and environmental factors, highlighting the need for targeted interventions [6].…”

Section: Introductionmentioning

confidence: 99%

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A Healthful Plant-Based Diet as an Alternative Dietary Approach in the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease

Castelnuovo,

Perez-Diaz-del-Campo,

Rosso

et al. 2024

Nutrients

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Plant-based diets (PBDs) are gaining attention as a sustainable and health-conscious alternative for managing various chronic conditions, including metabolic dysfunction-associated steatotic liver disease (MASLD). In the absence of pharmacological treatments, exploring the potential of lifestyle modifications to improve biochemical and pathological outcomes becomes crucial. The adoption of PBDs has demonstrated beneficial effects such as weight control, increased metabolic health and improved coexisting diseases. Nonetheless, challenges persist, including adherence difficulties, ensuring nutritional adequacy, and addressing potential deficiencies. The aim of this review is to provide a comprehensive overview of the impact of PBDs on MASLD, emphasizing the need for tailored dietary interventions with professional support to optimize their effectiveness in preventing and treating metabolic diseases.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Healthful Plant-Based Diet as an Alternative Dietary Approach in the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease

Castelnuovo,

Perez-Diaz-del-Campo,

Rosso

et al. 2024

Nutrients

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The beneficial hepatic effects of glucagon‐like peptide 1 receptor agonists in patients with diabetes and metabolic dysfunction‐associated steatotic liver disease are independent of weight loss

Forlano,

Malik,

Mullish

et al. 2024

Liver International Communications

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BackgroundMetabolic dysfunction‐associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide. Despite resmetirom being recently approved for treatingnon‐cirrhotic MASH patients in the United States of America (but not elsewhere), weight loss and lifestyle remain the first line and mainstay for treating the condition. Glucagon‐like peptide 1 receptor agonists (GLP‐1RAs) have shown promise in MASLD treatment, as they promote significant weight loss.AimsIn this study, we assessed the effect of long‐term GLP‐1 therapy on liver disease severity in a cohort of patients with Type 2 diabetes and MASLD.Materials and methodsIn this retrospective observational study, we included all new MASLD patients seen in the liver clinic (Imperial College Healthcare NHS Trust) from January 2010 to May 2022. Demographic, anthropometric and clinical data were collected at baseline and at the most recent follow‐up.Results779 patients were included. Among those with Type 2 diabetes mellitus (T2DM) (n = 335), 94 (28%) were prescribed a GLP‐1RA for a median period of 38 (1–171.2) months. In those on GLP‐1RA, there was a significant improvement in BMI (33.1 vs. 34.9 kg/m2, p = 0.005), alanine aminotransferase (ALT) (37 vs. 58 IU/L, p = 0.009), HbA1c (58 vs. 61 mmol/lL, p = 0.006) and CAP score (331 vs. 354 dB/m, p = 0.0001) at the end of follow‐up. Finally, among those who were treated with GLP‐1RA, 37 patients had <5% weight loss over a median of 38 (10–134) months. In this group, there was also a significant reduction in ALT (32 vs. 58 IU/L, p = 0.0001), AST (30 vs. 36 IU/L, p = 0.004) and CAP score (329 vs. 349 dB/m, p = 0.05) compared with those who lost >5% weight. In this real‐life cohort of patients with diabetes and MASLD, treatment with GLP‐1RA was associated with greater weight loss and hepatic fat reduction. Of note, a reduction in fat content was observed also in those who did not lose weight.ConclusionTreatment with GLP‐1RA should be favoured when treating patients with co‐existing diabetes and MASLD.

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Exposure–response modeling of liver fat imaging endpoints in non‐alcoholic fatty liver disease populations administered ervogastat alone and co‐administered with clesacostat

Hughes,

Amin,

Wojciechowski

et al. 2024

CPT Pharmacom & Syst Pharma

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Non‐alcoholic fatty liver disease and non‐alcoholic steatohepatitis describe a collection of liver conditions characterized by the accumulation of liver fat. Despite biopsy being the reference standard for determining the severity of disease, non‐invasive measures such as magnetic resonance imaging proton density fat fraction (MRI‐PDFF) and FibroScan® controlled attenuation parameter (CAP™) can be used to understand longitudinal changes in steatosis. The aim of this work was to describe the exposure–response relationship of ervogastat with or without clesacostat on steatosis, through population pharmacokinetic/pharmacodynamic (PK/PD) modeling of both liver fat measurements simultaneously. Population pharmacokinetic and exposure–response models using individual predictions of average concentrations were used to describe ervogastat/clesacostat PKPD. Due to both liver fat endpoints being continuous‐bounded outcomes on different scales, a dynamic transform‐both‐sides approach was used to link a common latent factor representing liver fat to each endpoint. Simultaneous modeling of both MRI‐PDFF and CAP™ was successful with both measurements being adequately described by the model. The clinical trial simulation was able to adequately predict the results of a recent Phase 2 study, where subjects given ervogastat/clesacostat 300/10 mg BID for 6 weeks had a LS means and model‐predicted median (95% confidence intervals) percent change from baseline MRI‐PDFF of −45.8% and −45.6% (−61.6% to −31.8%), respectively. Simultaneous modeling of both MRI‐PDFF and CAP™ was successful with both measurements being adequately described. By describing the underlying changes of steatosis with a latent variable, this model may be extended to describe biopsy results from future studies.

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EASL–EASD–EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD)

Cited by 113 publications

References 515 publications

A Healthful Plant-Based Diet as an Alternative Dietary Approach in the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease

A Healthful Plant-Based Diet as an Alternative Dietary Approach in the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease

The beneficial hepatic effects of glucagon‐like peptide 1 receptor agonists in patients with diabetes and metabolic dysfunction‐associated steatotic liver disease are independent of weight loss

Exposure–response modeling of liver fat imaging endpoints in non‐alcoholic fatty liver disease populations administered ervogastat alone and co‐administered with clesacostat

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