A global action agenda for turning the tide on fatty liver disease DOI Creative Commons
Jeffrey V. Lazarus, Henry E. Mark, Alina M. Allen

et al.

Hepatology, Journal Year: 2023, Volume and Issue: 79(2), P. 502 - 523

Published: Aug. 4, 2023

Background and Aims: Fatty liver disease is a major public health threat due to its very high prevalence related morbidity mortality. Focused dedicated interventions are urgently needed target prevention, treatment, care. Approach Results: We developed an aligned, prioritized action agenda for the global fatty community of practice. Following Delphi methodology over 2 rounds, large panel (R1 n = 344, R2 288) reviewed priorities using Qualtrics XM, indicating agreement 4-point Likert-scale providing written feedback. Priorities were revised between in R2, panelists also ranked within 6 domains: epidemiology, treatment care, models education awareness, patient perspectives, leadership policy. The consensus encompasses 29 priorities. In mean percentage “agree” responses was 82.4%, with all individual having at least super-majority (> 66.7% “agree”). highest-ranked included collaboration specialists primary care doctors on early diagnosis, address needs people living multiple morbidities, incorporation into relevant non-communicable strategies guidance. Conclusions: This consensus-driven multidisciplinary by providers, clinical researchers, policy experts provides path reduce improve outcomes. To implement this agenda, concerted efforts will be global, regional, national levels.

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

314
Lifestyle interventions in nonalcoholic fatty liver disease DOI
Zobair M. Younossi, Shira Zelber‐Sagi, Linda Henry

et al.

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2023, Volume and Issue: 20(11), P. 708 - 722

Published: July 4, 2023

Language: Английский

Citations

136
Biomarkers for staging fibrosis and non-alcoholic steatohepatitis in non-alcoholic fatty liver disease (the LITMUS project): a comparative diagnostic accuracy study DOI Creative Commons
Yasaman Vali, Jenny Lee, Jérôme Boursier

et al.

˜The œLancet. Gastroenterology & hepatology, Journal Year: 2023, Volume and Issue: 8(8), P. 714 - 725

Published: March 21, 2023

Language: Английский

Citations

95
A global research priority agenda to advance public health responses to fatty liver disease DOI Creative Commons
Jeffrey V. Lazarus, Henry E. Mark, Alina M. Allen

et al.

Journal of Hepatology, Journal Year: 2023, Volume and Issue: 79(3), P. 618 - 634

Published: June 20, 2023

An estimated 38% of adults worldwide have non-alcoholic fatty liver disease (NAFLD). From individual impacts to widespread public health and economic consequences, the implications this are profound. This study aimed develop an aligned, prioritised research agenda for global community.

Language: Английский

Citations

69
Critical appraisal of metabolic dysfunction-associated steatotic liver disease: Implication of Janus-faced modernity DOI Creative Commons
Gi‐Ae Kim, Joon Ho Moon, Won Kim

et al.

Clinical and Molecular Hepatology, Journal Year: 2023, Volume and Issue: 29(4), P. 831 - 843

Published: Aug. 27, 2023

The existing term non-alcoholic fatty liver disease (NAFLD) has raised substantial concerns due to its inherent disadvantages of using exclusionary diagnostic criteria and the stigmatizing word 'fatty.' Three pan-national associations set out explore a new nomenclature replace both NAFLD suggested alternative, metabolic (dysfunction)-associated (MAFLD). They surveyed if change in and/or definition is favored which best communicates characteristics increases awareness. In lieu NAFLD/MAFLD, dysfunction-associated steatotic (MASLD) been chosen, an umbrella term, (SLD), encompassing whole spectrum disease, proposed. It that cardiometabolic risk factors should be considered when categorizing SLD patients. Furthermore, subcategory, MASLD with increased alcohol intake (MetALD), casts light on neglected group patients moderate or more consumption. importance dysfunction was acknowledged this nomenclature, but precise contribution consumption development progression remains unclear. Herein, we review hepatologists' endocrinologists' perspectives along possible impact clinical practice. Although it premature predict settlement may help build evidence for soft landing future.

Language: Английский

Citations

67
The first MASH drug therapy on the horizon: Current perspectives of resmetirom DOI Creative Commons
Salvatore Petta, Giovanni Targher, Stefano Romeo

et al.

Liver International, Journal Year: 2024, Volume and Issue: 44(7), P. 1526 - 1536

Published: April 5, 2024

Abstract The rising prevalence of metabolic dysfunction‐associated steatotic liver disease (MASLD) poses a significant global health challenge, affecting over 30% adults worldwide. MASLD is linked to increased mortality rates and substantial healthcare costs, primarily driven by its progression steatohepatitis (MASH), which can lead severe complications including cirrhosis hepatocellular carcinoma. Despite growing burden, effective pharmacotherapy for MASLD/MASH has been lacking until the recent conditional approval resmetirom FDA. Resmetirom, liver‐targeted thyroid hormone receptor‐β selective drug, shown promise in clinical trials treating non‐cirrhotic MASH with moderate advanced fibrosis. It demonstrated efficacy reducing hepatic fat content, improving histology (both resolution fibrosis improvement), ameliorating biomarkers damage without effects on body weight or glucose metabolism. Notably, also exhibits favourable circulating lipids, potentially cardiovascular risk patients. safety profile appears acceptable, gastrointestinal adverse events being most common, though generally mild moderate. However, long‐term surveillance warranted monitor potential risks related thyroid, gonadal, bone diseases. Clinical implementation faces challenges patient selection monitoring treatment response, will heavily rely non‐invasive tests assessment. Nonetheless, represents landmark breakthrough treatment, paving way future therapeutic strategies aiming mitigate multifaceted associated this complex disease.

Language: Английский

Citations

63
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

59
Ubiquitin-Specific Proteases (USPs) and Metabolic Disorders DOI Open Access
Hiroshi Kitamura

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3219 - 3219

Published: Feb. 6, 2023

Ubiquitination and deubiquitination are reversible processes that modify the characteristics of target proteins, including stability, intracellular localization, enzymatic activity. Ubiquitin-specific proteases (USPs) constitute largest deubiquitinating enzyme family. To date, accumulating evidence indicates several USPs positively negatively affect metabolic diseases. USP22 in pancreatic β-cells, USP2 adipose tissue macrophages, USP9X, 20, 33 myocytes, USP4, 7, 10, 18 hepatocytes, hypothalamus improve hyperglycemia, whereas USP19 adipocytes, USP21 USP2, 14, 20 hepatocytes promote hyperglycemia. In contrast, USP1, 5, 9X, 15, 22, 36, 48 modulate progression diabetic nephropathy, neuropathy, and/or retinopathy. ameliorates non-alcoholic fatty liver disease (NAFLD), while hepatic 11, 19, exacerbate it. The roles USP7 22 disorders controversial. 17, vascular cells postulated to be determinants atherosclerosis. Moreover, mutations

Language: Английский

Citations

56
Outcomes of Various Classes of Oral Antidiabetic Drugs on Nonalcoholic Fatty Liver Disease DOI
Heejoon Jang, Yeonjin Kim,

Dong Hyeon Lee

et al.

JAMA Internal Medicine, Journal Year: 2024, Volume and Issue: 184(4), P. 375 - 375

Published: Feb. 12, 2024

Importance Several oral antidiabetic drug (OAD) classes can potentially improve patient outcomes in nonalcoholic fatty liver disease (NAFLD) to varying degrees, but clinical data on which class is favored are lacking. Objective To investigate OAD associated with the best NAFLD and type 2 diabetes (T2D). Design, Setting, Participants This retrospective nonrandomized interventional cohort study used National Health Information Database, provided population-level for Korea. involved patients T2D concomitant NAFLD. Exposures Receiving either sodium-glucose cotransporter (SGLT2) inhibitors, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) or sulfonylureas, each combined metformin 80% more of 90 consecutive days. Main Outcomes Measures The main were regression assessed by index composite liver-related outcome (defined as hospitalization, mortality, transplant, hepatocellular carcinoma) using Fine-Gray model regarding competing risks. Results In total, 80 178 (mean [SD] age, 58.5 [11.9] years; 43 007 [53.6%] male) followed up 219 941 person-years, 4102 experiencing regression. When compared SGLT2 inhibitors (adjusted subdistribution hazard ratio [ASHR], 1.99 [95% CI, 1.75-2.27]), thiazolidinediones (ASHR, 1.70 1.41-2.05]), DPP-4 1.45 1.31-1.59]) a higher likelihood when 1.40 1.12-1.75]) 1.30-1.62]). Only 0.37 0.17-0.82]), not significantly lower incidence rates adverse sulfonylureas. Conclusions Relevance results this suggest that physicians may lean towards prescribing preferred individuals T2D, considering their potential benefits incidences outcomes. observational should prompt future research determine whether practices might merit reexamination.

Language: Английский

Citations

38
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

36