Metabolic Dysfunction and Alcohol-related Liver Disease (MetALD): Position statement by an expert panel on alcohol-related liver disease

Journal of Hepatology, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 1, 2024

Язык: Английский

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Global Epidemiology of Alcohol-Related Liver Disease, Liver Cancer, and Alcohol Use Disorder, 2000–2021

Clinical and Molecular Hepatology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 9, 2025

Alcohol represents a leading burden of disease worldwide, including alcohol use disorder (AUD) and alcohol-related liver (ALD). We aim to assess the global AUD, ALD, alcohol-attributable primary cancer between 2000-2021. registered regional trends using data from Global Burden Disease 2021 Study, largest most up-to-date epidemiology database. estimated annual percent change (APC) its 95% confidence interval (CI) changes in age-standardized rates over time. In 2021, there were 111.12 million cases 3.02 132,030 cancer. Between 2000 was 14.66% increase 38.68% 94.12% prevalence. While prevalence rate for increased (APC: 0.59%, [CI] 0.52 0.67%) these years, it decreased ALD -0.71%, CI -0.75 -0.67%) AUD -0.90%, -0.94 -0.86%). There significant variation by region, socioeconomic development level, sex. During last years (2019-2021), prevalence, incidence, death greater extent females. Given high cancer, urgent measures are needed prevent them at both national levels.

Язык: Английский

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Management of alcohol use disorder: a gastroenterology and hepatology-focused perspective

˜The œLancet. Gastroenterology & hepatology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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Clinical Trial to Assess the Safety and Tolerability of Anti‐IL 23 Monoclonal Antibody Guselkumab in Patients With Alcohol‐Associated Liver Disease

Alimentary Pharmacology & Therapeutics, Год журнала: 2025, Номер unknown

Опубликована: Фев. 14, 2025

ABSTRACT Background There are no FDA‐approved therapies for alcohol‐associated liver disease (ALD). Preclinical studies indicate that blocking IL‐23/IL‐17 signalling may reverse injury. Guselkumab, an IL‐23‐specific antibody approved psoriasis, be beneficial ALD. Aims We aimed to assess the safety and tolerability of guselkumab in patients with Methods This phase‐1 dose‐escalation study included ≥ 2 DSM‐5 criteria alcohol use disorder, significant steatosis (MRI‐PDFF 8%) MRE < 3.63 kPa (to exclude advanced disease). Guselkumab was given subcutaneously on Days 1 29 30, 70 or 100 mg dose cohorts. Primary endpoints were adverse events (AEs) dose‐limiting toxicity. Results enrolled 13 (three 30 mg, three seven mg). Eleven completed two early discontinued group. Of them, 77% men, median age 53 [IQR 49–61] years. The MRI‐PDFF 18.4% 8.4%–34.0%] 2.5 [2.2–2.6] kPa, respectively. most frequent AEs hyperuricemia (13%, mild only) elevated lipase (11%, moderate). serious variations enzymes. a suppression peripheral interleukin (IL)‐17, IL‐23, IL‐1b TNF‐α groups, decrease consumption over time (AUDIT‐C: 6 [3–7] vs. 5 [1–6], p = 0.023). Conclusions is safe doses up reduce inflammation markers These findings support further phase evaluate efficacy ALD, particularly severe phenotypes.

Язык: Английский

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Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease

World Journal of Gastroenterology, Год журнала: 2024, Номер 30(28), С. 3428 - 3446

Опубликована: Июль 24, 2024

BACKGROUND Alcohol-associated liver disease (ALD) is a leading cause of liver-related morbidity and mortality, but there are no therapeutic targets modalities to prevent ALD-related fibrosis. Peroxisome proliferator activated receptor (PPAR) α δ play key role in lipid metabolism intestinal barrier homeostasis, which major contributors the pathological progression ALD. Meanwhile, elafibranor (EFN), dual PPARα PPARδ agonist, has reached phase III clinical trial for treatment metabolic dysfunction-associated steatotic primary biliary cholangitis. However, benefits EFN ALD unknown. AIM To evaluate inhibitory effects on fibrosis gut-intestinal dysfunction an mouse model. METHODS was induced female C57BL/6J mice by feeding 2.5% ethanol (EtOH)-containing Lieber-DeCarli liquid diet intraperitoneally injecting carbon tetrachloride thrice weekly (1 mL/kg) 8 weeks. (3 10 mg/kg/day) orally administered during experimental period. Histological molecular analyses were performed assess effect steatohepatitis, fibrosis, integrity. The HepG2 lipotoxicity Caco-2 function evaluated cell-based assays. RESULTS hepatic steatosis, apoptosis, model significantly attenuated treatment. promoted lipolysis β-oxidation enhanced autophagic antioxidant capacities EtOH-stimulated cells, primarily through activation. Moreover, inhibited Kupffer cell-mediated inflammatory response, with blunted exposure lipopolysaccharide (LPS) toll like 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling. improved hyperpermeability restoring tight junction proteins autophagy inhibiting apoptosis proinflammatory responses. protective cells predominantly mediated CONCLUSION reduced accumulation enhancing hepatocyte capacities, suppressing LPS/TLR4/NF-κB-mediated responses function.

Язык: Английский

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Alcohol-related liver disease: A global perspective

Annals of Hepatology, Год журнала: 2024, Номер 29(5), С. 101499 - 101499

Опубликована: Апрель 4, 2024

Alcohol-associated liver disease (ALD) represents one of the deadliest yet preventable consequences excessive alcohol use. It 5.1% global burden disease, mainly involving productive-age population (15-44 years) and leading to an increased mortality risk from traffic road injuries, suicide, violence, cardiovascular neoplasms, among others, accounting for 5.3% deaths. Daily consumption, binge drinking (BD), heavy episodic (HED) are patterns associated with a higher developing ALD. The escalating ALD, even exceeding what was predicted, is result complex interaction between lack public policies that regulate low awareness scope late referral specialists, underuse available medications, insufficient funds allocated ALD research, non-predictable events such as COVID-19 pandemic, where increases up 477% in online sales were registered United States. Early diagnosis, referral, treatment pivotal achieving therapeutic goal patients use disorder (AUD) complete abstinence prevention relapse expected enhance overall survival. This can be achieved through combination cognitive behavioral, motivational enhancement pharmacological therapy. Furthermore, appropriate therapy implementation comprehensively address this will make real difference.

Язык: Английский

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An Update on Animal Models of Alcohol-Associated Liver Disease

American Journal Of Pathology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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NLRP3 and Gut–Liver Axis: New Possibility for the Treatment of Alcohol‐Associated Liver Disease

Journal of Gastroenterology and Hepatology, Год журнала: 2025, Номер unknown

Опубликована: Март 17, 2025

ABSTRACT Alcohol‐associated liver disease (ALD) is one of the most prevalent chronic diseases worldwide, with persistently high morbidity and mortality rates. Previous studies have identified NLRP3 inflammasome as a class receptors intracellular intrinsic immunity. These can be activated by both extracellular danger signals, leading to release downstream pro‐inflammatory factors, including interleukin IL‐1β IL‐18. vesicles are critical for maintaining host defense. Concurrently, researchers close relationship between microbiome, gut–liver axis, ALD. Consequently, present study focus on structure activation inflammasome, intestinal microecological regulation, well bile acid metabolism axis. The objective this provide foundation knowledge references development targeted therapeutic interventions ALD that informed dynamic interplay

Язык: Английский

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Periodontal disease and cirrhosis: current concepts and future prospects

eGastroenterology, Год журнала: 2025, Номер 3(1), С. e100140 - e100140

Опубликована: Фев. 1, 2025

Periodontal diseases are prevalent among the general population and associated with several systemic conditions, such as chronic kidney disease type 2 diabetes mellitus. Chronic liver cirrhosis have also been linked periodontal disease, an association complex underlying mechanisms, potential prognostic implications. Multiple factors can explain this relevant association, including nutritional factors, alcohol consumption, disruption of oral-gut-liver axis dysbiosis. Additionally, patients observed to exhibit poorer oral hygiene practices compared population, potentially predisposing them development disease. Therefore, it is recommended that all undergo screening subsequent treatment for Treatment in may help reduce liver-derived inflammatory damage, recent research indicating a benefit terms reduced mortality. However, further studies on still warranted determine optimal management strategies. This narrative review describes current concepts between

Язык: Английский

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Updated recommendations for the management of metabolic dysfunction–associated steatotic liver disease (MASLD) by the Latin American working group.

Annals of Hepatology, Год журнала: 2025, Номер unknown, С. 101903 - 101903

Опубликована: Март 1, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the leading causes chronic globally. Based on 2023 definition, MASLD characterized by presence metabolic dysfunction and limited alcohol consumption (<140 grams/week for women, <210 men). Given significant burden in Latin America, this guidance was developed American Association Study Liver (ALEH) Working Group to address key aspects its clinical assessment therapeutic strategies. In ultrasonography recommended as initial screening tool hepatic steatosis due accessibility, while Fibrosis-4 (FIB-4) preferred fibrosis risk stratification, with further evaluation using more specific techniques (i.e., vibration-controlled transient elastography or Enhanced Fibrosis [ELF] test). A Mediterranean diet advised all patients, a target 7-10% weight loss those excess weight. Complete abstinence patients fibrosis, smoking cessation encouraged regardless stage. Pharmacological options should be tailored based steatohepatitis, weight, diabetes, including resmetirom, incretin-based therapies, pioglitazone, sodium-glucose cotransporter-2 inhibitors. Bariatric surgery may considered obesity unresponsive lifestyle medical interventions. Hepatocellular carcinoma cirrhotic consideration given advanced individual risk. Finally, routine cardiovascular proper diabetes prevention management remain crucial MASLD.

Язык: Английский

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