NAFLD Fibrosis Progression and Type 2 Diabetes: The Hepatic–Metabolic Interplay

Life, Год журнала: 2024, Номер 14(2), С. 272 - 272

Опубликована: Фев. 18, 2024

The bidirectional relationship between type 2 diabetes and (non-alcoholic fatty liver disease) NAFLD is indicated by the higher prevalence worse disease course of one condition in presence other, but also apparent beneficial effects observed one, when other improved. This partly explained their belonging to a multisystemic that includes components metabolic syndrome shared pathogenetic mechanisms. Throughout progression more advanced stages, complex systemic local derangements are involved. During fibrogenesis, significant reprogramming occurs hepatic stellate cells, hepatocytes, immune engaging carbohydrate lipid pathways support high-energy-requiring processes. natural history evolves variable dynamic manner, probably due interaction number modifiable (diet, physical exercise, microbiota composition, etc.) non-modifiable (genetics, age, ethnicity, risk factors may intervene concomitantly, or subsequently/intermittently time. influence (and rate) fibrosis progression/regression. recognition control determine rapid (or its regression) critical, as stages associated with liver-related all-cause mortality.

Язык: Английский

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The impact of genetic risk on the prevalence of advanced fibrosis and cirrhosis in prospectively assessed patients with type 2 diabetes

Alimentary Pharmacology & Therapeutics, Год журнала: 2024, Номер 60(3), С. 369 - 377

Опубликована: Июнь 2, 2024

Summary Background Genetic factors contribute to the risk and severity of metabolic dysfunction‐associated steatotic liver disease (MASLD). However, utility genetic testing in stratification remains poorly characterised. Aims To examine influence on advanced fibrosis cirrhosis patients with type 2 diabetes mellitus (T2DM) a polygenic score (PRS) screening guidelines. Methods We prospectively enrolled adults aged ≥50 years T2DM recruited from clinics. PRS was sum alleles PNPLA3 , TM6SF2 SERPINA1 minus protective variant HSD17B13 . performed magnetic resonance elastography vibration‐controlled transient assess for cirrhosis. Results Of 382 included patients, mean age BMI were 64.8 (±8.4) 31.7 (±6.2) kg/m respectively. The prevalence 12.3% 5.2% respectively; higher associated increased (2.7% vs. 7.5%, p = 0.037). High among those fibrosis‐4 index (FIB‐4) <1.3 (9.6% 2.3%, 0.036) but not significantly different other FIB‐4 categories. Incorporating determination into American Gastroenterological Association Study Liver Diseases guidelines prevented approximately 20% all participants being inappropriately classified as low risk. Conclusions Utilising well‐phenotyped, prospective cohort T2DM, we found that adding an assessment recommendations screen at‐risk populations may improve prediction.

Язык: Английский

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A phase IIb randomised-controlled trial of the FFAR1/FFAR4 agonist icosabutate in MASH

Journal of Hepatology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Via regulation of glycemic control and inflammation, free fatty receptor (FFAR)1 4 are potential targets for the treatment MASH. This study tested efficacy safety icosabutate, a FFAR1/FFAR4 agonist, in MASH patients. We performed phase 2b, multicenter, 52-week, randomised, placebo-controlled trial (ICONA) testing icosabutate patients with F1-F3 (mild to severe) fibrosis. Patients were randomized 1:1:1 receive once-daily, oral 300 mg, 600 mg or placebo 52 weeks. The primary endpoint was proportion resolution no worsening fibrosis arm. population analysis comprised 187 [placebo (n=62), (n= 58) (n=67)]. percentage favoured arm without reaching statistical significance (23.9% vs. 14.5%; odds ratio, 2.01; 95% confidence interval [CI], 0.8 5.08; P=0.13). A higher treated achieved ≥1-stage improvement fibrosis, response rate 29.3% (odds 2.89; CI, 1.09 7.70))and 23.9% 2.4; 0.90 6.37)) 11.3% An observed using AI-assisted digital pathology. Marked decreases biomarkers liver damage observed. Icosabutate generally safe well tolerated, mild moderate TEAEs reports drug induced injury. Although not met, demonstrated encouraging (as measured by both conventional pathology) non-invasive biomarker data, supporting further development NCT04052516 IMPACT AND IMPLICATIONS: • With expression on multiple cells types regulating targeting acid receptors 1 could offer an attractive approach fibrosing it's comorbidities.• (a agonist) did meet pre-defined (MASH fibrosis), overall dataset (including suggest patients.• Improvements damage, inflammation therapy.• well-tolerated, data support patients, particular those more advanced disease (F2-F3 fibrosis) type 2 diabetes.

Язык: Английский

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Reviewing MAESTRO-NASH and the implications for hepatology and health systems in implementation/accessibility of Resmetirom

npj gut and liver., Год журнала: 2025, Номер 2(1)

Опубликована: Янв. 22, 2025

Язык: Английский

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Cardiovascular events and incident diabetes in 220 patients with MASLD according to basal liver fibrosis: a 10-year follow-up historic cohort

European Journal of Gastroenterology & Hepatology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 20, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) patients have a higher incidence of cardiovascular events (CVE) compared to controls. Aim The aim this study is analyze association between fibrosis with CVE, incident diabetes, and cirrhosis complications. Methods Historic cohort biopsy-proven MASLD patients, divided into two groups: F0–F2 vs F3–F4 fibrosis. Baseline data included metabolic traits function tests. Patients were contacted scheduled for laboratory analysis elastography. Endpoints (a) defined as any acute myocardial infarction, coronary stenting, ischemic cardiopathy, stroke; (b) diabetes; (c) collected at the time biopsy, while follow-up recovered through personal interview or medical records. A stepwise logistic regression determined predictive variables each endpoint. Results Study population 220 median age 53 years, 145 women; baseline was in 165 55 patients; 9.9 years. percentage had CVE (29.4%) than ones (13.1%) (hazard ratio 2.42; 95% CI: 1.26–4.6; P = 0.008). Incident diabetes occurred 53.3% 20.2% 3.04; 1.99–4.86; < 0.001); complications 9/55 1/165 26.3; 3.3–208.3; 0.002). Multivariate confirmed an independent predictor associated aspartate aminotransferase (AST)/alanine (ALT) ratio. Conclusion In followed AST/ALT CVE.

Язык: Английский

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