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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Hepatocellular carcinoma: updates on epidemiology, surveillance, diagnosis and treatment

Clinical and Molecular Hepatology, Год журнала: 2024, Номер unknown

Опубликована: Дек. 26, 2024

Hepatocellular carcinoma (HCC) is a major global burden, ranking as the third leading cause of cancer-related mortality.HCC due to chronic hepatitis B virus (HBV) or C (HCV) infection has decreased universal vaccination for HBV and effective antiviral therapy both HCV, but HCC related metabolic dysfunction associated steatotic liver disease (MASLD) alcohol-associated (ALD) increasing.Biannual ultrasonography serum α-fetoprotein are primary surveillance tools early detection among high-risk patients (e.g., cirrhosis, HBV).Alternative such blood-based biomarker panels abbreviated MRIs being investigated.Multiphasic CT MRI standard diagnosis, histological confirmation should be considered, especially when inconclusive findings seen on cross-sectional imaging.Staging treatment decisions complex made in multidisciplinary settings, incorporating multiple factors including tumor degree dysfunction, patient performance status, available expertise, preferences.Early-stage best treated with curative options resection, ablation, transplantation.For intermediatestage disease, locoregional therapies primarily recommended although systemic may preferred large intrahepatic burden.In advanced-stage immune checkpoint inhibitor (ICI)-based regimen.In this review article, we discuss recent epidemiology, risk factors, care continuum encompassing surveillance, staging, treatments.

Язык: Английский

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Editorial: Steatotic Liver Diseases Emerge as Rapidly Growing Drivers of Primary Liver Cancer in the United States—Author's Reply

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

Опубликована: Янв. 23, 2025

We extend our sincere gratitude for the recent editorial highlighting manuscript [1]. In study titled 'Alcohol-Related Liver Disease, Followed by Metabolic Dysfunction-Associated Steatotic Emerges as Fastest-Growing Aetiologies Primary Cancer in United States', we analysed prevalence, incidence and mortality trends of primary liver cancer (PLC) States using data from Global Burden Disease (GBD) 2021 database [2]. Our findings emphasise increasing contribution steatotic disease–related PLC to overall burden States, although chronic hepatitis C virus (HCV) infection remains leading contributor PLC. also acknowledge limitations raised Torosian et al. [1], particularly inability GBD evaluate based on race, ethnicity, histological subtypes or distinctions between metabolic dysfunction–associated alcohol-associated disease (MetALD) [3]. Future iterations should strive incorporate these subgroups provide a more nuanced understanding. Despite advancements management, progress identifying at-risk individuals achieving early detection HCC populations has not kept pace with treatment innovations, associated (SLD) [4, 5]. For instance, prior meta-analyses demonstrated that SLD-associated hepatocellular carcinoma is significantly less likely be detected screening often diagnosed at advanced stage compared other etiologies [6, 7]. Beyond improving screening, policy measures such alcohol taxation, pricing strategies reducing availability could play pivotal role alleviating [8]. dysfunction-associated steatohepatitis (MASH), it essential implement include intensive lifestyle interventions, pharmacological treatments slow prevent progression fibrosis [9]. Supporting patients MASH requires multidisciplinary approach, including expanded involvement nutritionists, social prescribing initiatives acknowledgement critical nutrition. These steps are addressing public health challenges posed MASLD, MASH-associated [10]. The elimination HCV sustained momentum continues contribute global burden. However, attainable due HCV's distinct characteristics, reliable diagnostic tests cost-effective cost-saving interventions. Key blood donors HCV, promoting safe injection practices, enforcing robust infection-control programmes minimise transmission providing effective antiviral those infected. summary, highlight need early, targeted interventions mitigate sustain eliminating HCV. Such efforts reduce synergistically. Pojsakorn Danpanichkul: writing – original draft. Donghee Kim: review editing. Chun Wei Pan: Amit G. Singal: Ju Dong Yang: Karn Wijarnpreecha: authors' declarations personal financial interests unchanged article This linked Danpanichkul al papers. To view articles, visit https://doi.org/10.1111/apt.18473 https://doi.org/10.1111/apt.18508. Data sharing applicable this no datasets were generated during current study.

Язык: Английский

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Women and People From Deprived Areas Are Less Likely to be Assessed for Liver Transplantation for Alcohol-related Liver Disease: Results From a National Study of Transplant Assessments

Transplantation Direct, Год журнала: 2025, Номер 11(3), С. e1761 - e1761

Опубликована: Фев. 7, 2025

Alcohol-related liver disease (ArLD) is the most common indication for transplantation in Europe and United States. Few studies have examined characteristics of patients with ArLD formally assessed transplants. We collected prospective data on every patient Kingdom during a 12-mo period. Five hundred forty-nine were transplantation. The median Model End-Stage Liver Disease (MELD) score was 15 UK MELD 54. 24% women. duration abstinence 12 mo. Listing outcomes 59% listed, 4% deferred, 37% not listed. reasons listing medical comorbidities (29%), too early (20%), potential recoverability (18%), recent alcohol use (12%), other (21%). Patients listed transplant had higher (16 versus 13; P < 0.001) scores (55 53; 0.001), longer (median 10 mo; = 0.026), no differences sex (P 0.258), age distribution 0.53), or deprivation deciles compared those Comparing to national deaths from revealed lower proportion female (24% 36% deaths; areas high (assessments: deaths, deprived decile 1:20 least 1:9). This study provides first complete profile evaluations ArLD. Women population may be relatively underrepresented.

Язык: Английский

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Global, Regional, And National Disease Burden Attributable To Liver Cancerdue to Alcohol Use in Elderly Adults Over 70 Years of Age from 1990-2021 and Projections to 2050

Опубликована: Янв. 1, 2025

Язык: Английский

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Liver transplantation for alcohol-associated liver disease: The changing landscape

Hepatology forum/Hepatology forum (Online), Год журнала: 2025, Номер unknown, С. 77 - 86

Опубликована: Янв. 1, 2025

Alcoholic liver disease(ALD) is considered as a growing public health issue with universally increasing disease burden. Various genetic and environmental factors play role in its etiology. ALD recently has become the major indication for Liver Transplantation (LT). Most LT programs select their candidates by adhering to six months of alcohol abstinence policy. Nevertheless, early transplantation (ELT) subject research, both Europe United States, an effective lifesaving option among highly selected severe alcohol-associated hepatitis (SAH) patients. ELT promising way management ALD, perhaps changing clinical practice carefully patient groups.

Язык: Английский

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Outcomes for patients with alcohol‐related liver disease admitted to Scottish intensive care units 2010–2018

Anaesthesia, Год журнала: 2025, Номер unknown

Опубликована: Март 11, 2025

Summary Introduction Alcohol‐related liver disease is recognised as a major cause of liver‐related morbidity and mortality. Our aim was to report the prevalence of, outcomes from, alcohol‐related after admission ICUs in Scotland. Methods We performed secondary data analysis using linked Scottish national databases all adult general compared emergency non‐surgical patients admitted ICU with without disease. The primary outcome mortality, were rate ratio; 60‐day mortality; 2‐year duration hospital stay; need for readmission. Results Of 49,420/103,103 (47.9%) diagnoses between 2010 2018, we identified 2629/49,420 (5.3%) Patients more likely receive three‐organ support (14.0% vs. 10.0%, p < 0.001). Mortality higher (964/2629 (36.7%) 10,517/46,791 (22.5%), respectively; aOR 2.03 (95%CI 1.85–2.24)). who specifically presented gastrointestinal bleed had lower mortality (95/487 (19.5%)). Sixty‐day increased levels organ (186/516 (36.0%) zero organs supported 162/196 (82.7%) three supported). Discussion Early high ICU, especially if multi‐organ required. However, nearly one‐fifth on survived discharge. considerably should be taken into consideration when considering management ICU. In discussion patient hepatologists, trial continuous re‐evaluation may appropriate.

Язык: Английский

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MetALD: New Perspectives on an Old Overlooked Disease

Liver International, Год журнала: 2025, Номер 45(5)

Опубликована: Апрель 3, 2025

ABSTRACT Metabolic dysfunction‐associated steatotic liver disease (MASLD) and alcohol‐associated (ALD) are the major contributors to burden globally. The rise in these conditions is linked obesity, type 2 diabetes, metabolic syndrome increased alcohol consumption. MASLD ALD share risk factors, pathophysiology histological features but differ their thresholds for use, definition does not require presence of dysfunction. A recent multi‐society consensus overhauled nomenclature steatosis introduced term MetALD describe patients with dysfunction who drink more than those less ALD. This new terminology aims enhance understanding management poses challenges, such as need accurately measure consumption research clinical practice settings. Recent studies show that has significant implications patient management, it associated mortality risks severe outcomes compared alone. face progression, cancer cardiovascular disease. diagnosis involves adequate quantification use through standardised questionnaires and/or biomarkers well proper assessment stage progression using non‐invasive tools including serologic markers, imaging, elastography techniques genetic testing. Effective requires addressing both alcohol‐related factors improve outcomes. review intends provide a comprehensive overview MetALD, covering pathogenesis, potential diagnostic approaches, strategies emerging therapies.

Язык: Английский

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Pemafibrate modulates peroxisome proliferator-activated receptor alpha and prevents alcohol-associated liver disease in rats

Molecular Medicine, Год журнала: 2025, Номер 31(1)

Опубликована: Апрель 22, 2025

Язык: Английский

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Challenges in the Management of Alcohol-Associated Liver Disease in Latin America

Annals of Hepatology, Год журнала: 2024, Номер unknown, С. 101748 - 101748

Опубликована: Ноя. 1, 2024

Язык: Английский

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