Estimated Burden of Metabolic Dysfunction–Associated Steatotic Liver Disease in US Adults, 2020 to 2050 DOI Creative Commons
Phuc Le, Moosa Tatar, Srinivasan Dasarathy

et al.

JAMA Network Open, Journal Year: 2025, Volume and Issue: 8(1), P. e2454707 - e2454707

Published: Jan. 17, 2025

Importance Metabolic dysfunction–associated steatotic liver disease (MASLD) is the most common cause of chronic and projected to become leading indication for transplant (LT) in US. Understanding its clinical burden can help identify opportunities prevention treatment. Objective To project MASLD US adults from 2020 2050. Design, Setting, Participants This decision analytical modeling study used an agent-based state transition model that simulates natural history progression among 18 years age or older. Primary data sources inputs were published literature. Exposure Natural MASLD. Main Outcomes Measures Cases MASLD, metabolic steatohepatitis (MASH), fibrosis, hepatocellular carcinoma (HCC), LT, liver-related death. Results The simulated 2 821 624 individuals (mean age. 35.8 years; 50.9% female). predicted a steady increase prevalence 33.7% (86.3 million people) 41.4% (121.9 by MASH would 14.9 (5.8% adults) 23.2 (7.9% number cases clinically significant fibrosis (ie, F≥F2, centrilobular periportal more severe disease) estimated 6.7 11.7 million. By 2046 2050, 22 440 new HCC 6720 LT per year compared with 11 483 1717 2025. Liver-related mortality was 30 500 deaths (1.0% all-cause 95 300 (2.4%) Conclusions Relevance In this study, forecast substantial over next 3 decades absence effective treatments. These results suggest health systems should plan large increases need LT.

Language: Английский

EASL–EASD–EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD) DOI Creative Commons
Frank Tacke, Paul Horn, Vincent Wai‐Sun Wong

et al.

Journal of Hepatology, Journal Year: 2024, Volume and Issue: 81(3), P. 492 - 542

Published: June 7, 2024

Language: Английский

Citations

296
Tirzepatide for Metabolic Dysfunction–Associated Steatohepatitis with Liver Fibrosis DOI
Rohit Loomba, Mark L. Hartman, Eric Lawitz

et al.

New England Journal of Medicine, Journal Year: 2024, Volume and Issue: 391(4), P. 299 - 310

Published: June 8, 2024

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease associated with liver-related complications and death. The efficacy safety of tirzepatide, an agonist the glucose-dependent insulinotropic polypeptide glucagon-like peptide-1 receptors, in patients MASH moderate or severe fibrosis unclear.

Language: Английский

Citations

188
A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis DOI

Arun J. Sanyal,

Pierre Bédossa,

Mandy Fraessdorf

et al.

New England Journal of Medicine, Journal Year: 2024, Volume and Issue: 391(4), P. 311 - 319

Published: June 7, 2024

BackgroundDual agonism of glucagon receptor and glucagon-like peptide-1 (GLP-1) may be more effective than GLP-1 alone for treating metabolic dysfunction–associated steatohepatitis (MASH). The efficacy safety survodutide (a dual agonist receptor) in persons with MASH liver fibrosis are unclear.MethodsIn this 48-week, phase 2 trial, we randomly assigned adults biopsy-confirmed stage F1 through F3 a 1:1:1:1 ratio to receive once-weekly subcutaneous injections at dose 2.4, 4.8, or 6.0 mg placebo. trial had two phases: 24-week rapid-dose-escalation phase, followed by maintenance phase. primary end point was histologic improvement (reduction) no worsening fibrosis. Secondary points included decrease fat content least 30% biopsy-assessed one stage.ResultsA total 293 participants received Improvement occurred 47% the 2.4-mg group, 62% those 4.8-mg 43% 6.0-mg as compared 14% placebo group (P<0.001 quadratic dose–response curve best-fitting model). A 63% 67% 57% group; 34%, 36%, 22%, respectively. Adverse events that were frequent nausea (66% vs. 23%), diarrhea (49% vomiting (41% 4%); serious adverse 8% 7% placebo.ConclusionsSurvodutide superior respect without fibrosis, warranting further investigation 3 trials. (Funded Boehringer Ingelheim; 1404-0043 ClinicalTrials.gov number, NCT04771273; EudraCT 2020-002723-11.)

Language: Английский

Citations

127
Safety and efficacy of once-weekly efruxifermin versus placebo in non-alcoholic steatohepatitis (HARMONY): a multicentre, randomised, double-blind, placebo-controlled, phase 2b trial DOI
Stephen A. Harrison, Juan P. Frías,

Guy Neff

et al.

˜The œLancet. Gastroenterology & hepatology, Journal Year: 2023, Volume and Issue: 8(12), P. 1080 - 1093

Published: Oct. 3, 2023

Language: Английский

Citations

91
EASL-EASD-EASO Clinical Practice Guidelines on the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) DOI Creative Commons
Frank Tacke, Paul Horn, Vincent Wai‐Sun Wong

et al.

Obesity Facts, Journal Year: 2024, Volume and Issue: 17(4), P. 374 - 444

Published: Jan. 1, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty (NAFLD), is defined as (SLD) in the presence of one or more cardiometabolic risk factor(s) and absence harmful alcohol intake. The spectrum MASLD includes steatosis, metabolic steatohepatitis (MASH, NASH), fibrosis, cirrhosis MASH-related hepatocellular carcinoma (HCC). This joint EASL-EASD-EASO guideline provides an update on definitions, prevention, screening, diagnosis treatment for MASLD. Case-finding strategies with using non-invasive tests, should be applied individuals factors, abnormal enzymes, and/or radiological signs hepatic particularly type 2 diabetes (T2D) obesity additional factor(s). A stepwise approach blood-based scores (such FIB-4) and, sequentially, imaging techniques transient elastography) suitable to rule-out/in advanced which predictive liver-related outcomes. In adults MASLD, lifestyle modification - including weight loss, dietary changes, physical exercise discouraging consumption well optimal management comorbidities use incretin-based therapies (e.g. semaglutide, tirzepatide) T2D obesity, if indicated advised. Bariatric surgery also option obesity. If locally approved dependent label, non-cirrhotic MASH significant fibrosis (stage ≥2) considered a MASH-targeted resmetirom, demonstrated histological effectiveness acceptable safety tolerability profile. No pharmacotherapy can currently recommended cirrhotic stage. Management adaptations drugs, nutritional counselling, surveillance portal hypertension HCC, transplantation decompensated cirrhosis.

Language: Английский

Citations

56
Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial DOI Creative Commons
Arun J. Sanyal, Lee M. Kaplan, Juan P. Frías

et al.

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(7), P. 2037 - 2048

Published: June 10, 2024

Abstract Retatrutide is a novel triple agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1 and glucagon receptors. A 48-week phase 2 obesity study demonstrated weight reductions 22.8% 24.2% with retatrutide 8 12 mg, respectively. The primary objective this substudy was to assess mean relative change from baseline in liver fat (LF) at 24 weeks participants that metabolic dysfunction-associated steatotic disease ≥10% LF. Here, randomized, double-blind, placebo-controlled trial, ( n = 98) were randomly assigned 48 once-weekly subcutaneous (1, 4, or mg dose) placebo. LF −42.9% (1 mg), −57.0% (4 −81.4% (8 −82.4% (12 mg) +0.3% (placebo) (all P < 0.001 versus placebo). At weeks, normal (<5%) achieved by 27% 52% 79% 86% 0% participants. significantly related changes body weight, abdominal measures associated improved insulin sensitivity lipid metabolism. ClinicalTrials.gov registration NCT04881760 .

Language: Английский

Citations

53
Obesity and its comorbidities, current treatment options and future perspectives: Challenging bariatric surgery? DOI Creative Commons

Simon Kloock,

Christian G. Ziegler,

Ulrich Dischinger

et al.

Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 251, P. 108549 - 108549

Published: Oct. 23, 2023

Obesity and its comorbidities, including type 2 diabetes mellitus, cardiovascular disease, heart failure non-alcoholic liver disease are a major health economic burden with steadily increasing numbers worldwide. The need for effective pharmacological treatment options is strong, but, until recently, only few drugs have proven sufficient efficacy safety. This article provides comprehensive overview of obesity special focus on organ-specific pathomechanisms. Bariatric surgery as the so far most-effective therapeutic strategy, current future strategies will be discussed. An knowledge about gut-brain axis especially identification physiology incretins unfolds high number potential drug candidates impressive weight-reducing potential. Future multi-modal concepts in may surpass effectivity bariatric not regard to weight loss, but also associated comorbidities.

Language: Английский

Citations

50
NAFLD and NASH: etiology, targets and emerging therapies DOI

Shulin Wei,

Li Wang, Paul C. Evans

et al.

Drug Discovery Today, Journal Year: 2024, Volume and Issue: 29(3), P. 103910 - 103910

Published: Feb. 1, 2024

Language: Английский

Citations

49
NASH drug treatment development: challenges and lessons DOI
Herbert Tilg, Christopher D. Byrne, Giovanni Targher

et al.

˜The œLancet. Gastroenterology & hepatology, Journal Year: 2023, Volume and Issue: 8(10), P. 943 - 954

Published: Aug. 16, 2023

Language: Английский

Citations

48
Therapeutic management of metabolic dysfunction associated steatotic liver disease DOI Creative Commons
Jing Zeng, Jian‐Gao Fan, Sven Francque

et al.

United European Gastroenterology Journal, Journal Year: 2024, Volume and Issue: 12(2), P. 177 - 186

Published: Jan. 9, 2024

Abstract The incidence and prevalence of non‐alcoholic fatty liver disease (NAFLD) have been steadily increasing worldwide, with a huge societal economic burden. Recently, NAFLD steatohepatitis renamed redefined as metabolic dysfunction associated steatotic (MASLD) (Metabolic Dysfunction Associated Steatohepatitis (MASH)), which result from an imbalance between inflammatory stress (mainly consequence adipose tissue insulin resistance) the defence repair mechanisms liver. Once MASLD progresses to end‐stage disease, treatment efficacy becomes limited may require transplantation. Early detection intervention are crucial. Lifestyle modification is consequently cornerstone its management. Timely consideration bariatric surgeries should be given patients meeting specific criteria. A multidisciplinary approach warranted, starting concept that MASLD/MASH at centre cardiovascular‐liver‐metabolic syndrome. In some cases, pharmacological can complement lifestyle modification. Several drugs used treat cardiometabolic co‐morbidities potential in slowing Down progression, demonstrated on histological endpoints likely translate into long‐term clinical benefits. Optimising use these within their licenced indications thus paramount for MASLD. MASH‐specific horizon enrich our therapeutic armamentarium near future, particularly non‐cirrhotic stages disease. Much work still needs done understand features MASH cirrhosis develop efficacious treatments this stage.

Language: Английский

Citations

35