Prospects of elafibranor in treating alcohol-associated liver diseases DOI

Wanzhen Cui,

Huadan Xue, Daimin Wei

et al.

World Journal of Gastroenterology, Journal Year: 2024, Volume and Issue: 31(2)

Published: Dec. 18, 2024

Alcohol-related liver disease (ALD), which is induced by excessive alcohol consumption, a leading cause of liver-related morbidity and mortality. ALD patients exhibit spectrum injuries, including hepatic steatosis, inflammation, fibrosis, similar to symptoms nonalcohol-associated diseases such as primary biliary cholangitis, metabolic dysfunction-associated steatotic disease, nonalcoholic steatohepatitis. Elafibranor has been approved for the treatment cholangitis shown improve in both animal models vitro cell However, efficacy elafibranor treating remains unclear. In this article, we comment on recent publication Koizumi et al that evaluated effects fibrosis gut barrier function an mouse model. Their findings indicate potential treatment, but further experimental investigations clinical trials are warranted.

Language: Английский

Management of alcohol use disorder: a gastroenterology and hepatology-focused perspective DOI
Luis Antonio Díaz, Daniel König, Sabine Weber

et al.

˜The œLancet. Gastroenterology & hepatology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

3
Clinical Trial to Assess the Safety and Tolerability of Anti‐IL 23 Monoclonal Antibody Guselkumab in Patients With Alcohol‐Associated Liver Disease DOI Open Access
Luis Antonio Díaz,

Sheldon Morris,

Shravan Dave

et al.

Alimentary Pharmacology & Therapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 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.

Language: Английский

Citations

2
Pharmacological and Nonpharmacological Interventions to Address Sleep Disturbance in Substance use Disorders DOI
Majd Al‐Soleiti, Meghna P. Mansukhani, Bhanu Prakash Kolla

et al.

Current Sleep Medicine Reports, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 29, 2025

Language: Английский

Citations

1
Incorporating genetic variations in alcohol-associated liver disease trials for East Asian populations DOI Creative Commons
Bo Seung Kang

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

Language: Английский

Citations

1
Treatment engagement in comorbid alcohol use disorder and alcohol‐related liver disease: A qualitative exploration of barriers and facilitators with service users DOI Creative Commons
Sofia Hemrage, Stephen Parkin, Nicola J. Kalk

et al.

Alcohol Clinical and Experimental Research, Journal Year: 2024, Volume and Issue: 48(10), P. 1965 - 1978

Published: Aug. 27, 2024

Effective interventions to improve patient outcomes in comorbid alcohol use disorder (AUD) and alcohol-related liver disease (ARLD) remain a clinical unmet need. While the choice of abstinence is cornerstone for prevention progression mortality, evidence suggests suboptimal engagement with treatment supporting recovery. This qualitative investigation aims understand barriers facilitators as experienced by this population applying multidimensional adherence model proposed World Health Organization.

Language: Английский

Citations

4
Larsucosterol Moves Forward as a Treatment Contender for Alcohol-Associated Hepatitis DOI
Praveena Narayanan,

Michael R. Lucey

NEJM Evidence, Journal Year: 2025, Volume and Issue: 4(2)

Published: Jan. 28, 2025

Language: Английский

Citations

0
Regulatory mechanisms of the probiotic-targeted gut–liver axis for the alleviation of alcohol-related liver disease: a review DOI

Feiyu Yang,

Xiangfei Li, Jing Sun

et al.

Critical Reviews in Food Science and Nutrition, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 22

Published: Feb. 5, 2025

Alcohol abuse-triggered alcohol-related liver disease (ALD) has become as a global public health concern that substantially affects the well-being and clinical status of patients. Although modern medicine provides various treatments for ALD, their effectiveness is limited can lead to adverse side effects. Probiotics have been employed prevent, alleviate, even treat with promising results. However, few comprehensive reviews are available on how they mitigate ALD by targeting gut-liver axis. This review systematically clarifies specific mediators axis in healthy states. It also describes alterations observed ALD. Furthermore, this thoroughly summarizes underlying mechanisms through which probiotics act relieve discusses current challenges faced research applications. Finally, we discuss future prospects using improves our understanding supports development application target therapeutic use.

Language: Английский

Citations

0
Gut Microbiome-Liver-Brain axis in Alcohol Use Disorder. The role of gut dysbiosis and stress in alcohol-related cognitive impairment progression: possible therapeutic approaches. DOI Creative Commons
Emilio Merlo Pich, Ioannis Tarnanas, Patrizia Brigidi

et al.

Neurobiology of Stress, Journal Year: 2025, Volume and Issue: 35, P. 100713 - 100713

Published: Feb. 8, 2025

The Gut Microbiome-Liver-Brain Axis is a relatively novel construct with promising potential to enhance our understanding of Alcohol Use Disorder (AUD), and its therapeutic approaches. Significant alterations in the gut microbiome occur AUD even before any other systemic signs or symptoms manifest. Prolonged inappropriate alcohol consumption, by affecting microbiota mucosa permeability, thought contribute development behavioral cognitive impairments, leading Alcohol-Related Liver Disorders potentially progressing into alcoholic cirrhosis, which often associated severe impairment related neurodegeneration, such as hepatic encephalopathy dementia. critical role further supported efficacy FDA-approved treatments for cirrhosis (i.e., lactulose rifaximin). To stimulate new research, we hypothesize that interactions between maladaptive stress response constitutional predisposition neurodegeneration underlie progression conditions Clinical Concerns impairment, represent significant costly burden society. Early identification individuals at risk developing these could help prioritize integrated interventions targeting different substrates axis. Specifically, addiction medications, modulators, stress-reducing interventions, and, possibly soon, agents reduce steatosis/fibrosis will be discussed context digitally explicit goal this treatment performed on early stage disorder would transition from those Common strategy recommended most neurological neurodegenerative disorders.

Language: Английский

Citations

0
Arrestin domain containing 3 promotes alcohol-induced liver steatosis by reducing stearoyl-CoA desaturase-1 ubiquitinated degradation DOI Creative Commons
Yin Tang, Haoxiong Zhou, Xuemei Pan

et al.

Metabolism, Journal Year: 2025, Volume and Issue: unknown, P. 156175 - 156175

Published: March 1, 2025

Language: Английский

Citations

0
Contingency management to promote treatment engagement in comorbid alcohol use disorder and alcohol‐related liver disease: Findings from a pilot randomized controlled trial DOI Creative Commons
Sofia Hemrage, Nicola J. Kalk,

Naina Shah

et al.

Alcohol Clinical and Experimental Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Abstract Background Alcohol‐related liver disease (ARLD) is a leading cause of preventable death and health inequalities. Evidence‐based interventions for comorbid alcohol use disorder (AUD) ARLD remain limited, only small proportion this clinical population engages with treatment. There need to improve patient outcomes by bridging gap through novel, person‐centred interventions. Contingency management (CM) psychosocial intervention that involves gradual, increasing incentives upon the completion treatment‐related goals, such as treatment attendance. This single‐centre, randomized pilot trial voucher‐based CM was conducted promote engagement in AUD ARLD. Methods Thirty service users were recruited from an inpatient setting, offered integrated care (ILC) allocated ILC or + CM. Primary included feasibility criteria (recruitment, study retention post‐randomization, completeness data protocol fidelity). Secondary outcome on engagement, intake, function also collected. Data gathered at baseline, post‐ILC, 12 weeks post‐ILC analyzed descriptive statistics. Results The research subject challenges inherent conducting applied real‐world setting. recruitment rates 73.20% 36.70%, respectively. All participants received per protocol. An trend observed compared (67% vs. 33%). A trending 76% reduction intake overall improvement among engaging trial, no significant differences between control groups. Conclusion Overall, feasible deliver appears promising improving individuals Aspects related recruitment, fidelity be further adapted before proceeding definitive trial.

Language: Английский

Citations

0