Clinical Gastroenterology and Hepatology, Год журнала: 2024, Номер 22(7), С. 1453 - 1461.e2
Опубликована: Фев. 29, 2024
Язык: Английский
Journal of Hepatology, Год журнала: 2024, Номер 81(3), С. 492 - 542
Опубликована: Июнь 7, 2024
Язык: Английский
Процитировано
296
Gut, Год журнала: 2024, Номер unknown, С. gutjnl - 330595
Опубликована: Янв. 16, 2024
Non-alcoholic fatty liver disease (NAFLD) has rapidly become the most common chronic globally and is currently estimated to affect up 38% of global adult population. NAFLD a multisystem where systemic insulin resistance related metabolic dysfunction play pathogenic role in development its relevant liver-related morbidities (cirrhosis, failure hepatocellular carcinoma) extrahepatic complications, such as cardiovascular (CVD), type 2 diabetes mellitus, kidney disease, certain types cancers. In 2023, three large multinational associations proposed that dysfunction-associated steatotic (MASLD) should replace term NAFLD; name chosen non-alcoholic steatohepatitis was (MASH). Emerging epidemiological evidence suggests an excellent concordance rate between MASLD definitions—that is, ~99% individuals with meet criteria. this narrative review, we provide overview literature on (a) recent data risk developing CVD malignant (b) underlying mechanisms by which (and factors strongly linked MASLD) may increase these complications (c) diagnosis assessment potential treatments reduce people or MASH.
Язык: Английский
Процитировано
242
New England Journal of Medicine, Год журнала: 2024, Номер 391(4), С. 311 - 319
Опубликована: Июнь 7, 2024
BackgroundDual agonism of glucagon receptor and glucagon-like peptide-1 (GLP-1) may be more effective than GLP-1 alone for treating metabolic dysfunction–associated steatohepatitis (MASH). The efficacy safety survodutide (a dual agonist receptor) in persons with MASH liver fibrosis are unclear.MethodsIn this 48-week, phase 2 trial, we randomly assigned adults biopsy-confirmed stage F1 through F3 a 1:1:1:1 ratio to receive once-weekly subcutaneous injections at dose 2.4, 4.8, or 6.0 mg placebo. trial had two phases: 24-week rapid-dose-escalation phase, followed by maintenance phase. primary end point was histologic improvement (reduction) no worsening fibrosis. Secondary points included decrease fat content least 30% biopsy-assessed one stage.ResultsA total 293 participants received Improvement occurred 47% the 2.4-mg group, 62% those 4.8-mg 43% 6.0-mg as compared 14% placebo group (P<0.001 quadratic dose–response curve best-fitting model). A 63% 67% 57% group; 34%, 36%, 22%, respectively. Adverse events that were frequent nausea (66% vs. 23%), diarrhea (49% vomiting (41% 4%); serious adverse 8% 7% placebo.ConclusionsSurvodutide superior respect without fibrosis, warranting further investigation 3 trials. (Funded Boehringer Ingelheim; 1404-0043 ClinicalTrials.gov number, NCT04771273; EudraCT 2020-002723-11.)
Язык: Английский
Процитировано
127
Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)
Опубликована: Май 27, 2023
The ever-increasing prevalence of noncommunicable diseases (NCDs) represents a major public health burden worldwide. most common form NCD is metabolic diseases, which affect people all ages and usually manifest their pathobiology through life-threatening cardiovascular complications. A comprehensive understanding the will generate novel targets for improved therapies across spectrum. Protein posttranslational modification (PTM) an important term that refers to biochemical specific amino acid residues in target proteins, immensely increases functional diversity proteome. range PTMs includes phosphorylation, acetylation, methylation, ubiquitination, SUMOylation, neddylation, glycosylation, palmitoylation, myristoylation, prenylation, cholesterylation, glutathionylation, S-nitrosylation, sulfhydration, citrullination, ADP ribosylation, several PTMs. Here, we offer review roles pathological consequences, including diabetes, obesity, fatty liver hyperlipidemia, atherosclerosis. Building upon this framework, afford description proteins pathways involved by focusing on PTM-based protein modifications, showcase pharmaceutical intervention preclinical studies clinical trials, future perspectives. Fundamental research defining mechanisms whereby regulate open new avenues therapeutic intervention.
Язык: Английский
Процитировано
97
JAMA, Год журнала: 2024, Номер 331(15), С. 1287 - 1287
Опубликована: Март 21, 2024
Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently the most common chronic worldwide. It important to develop noninvasive tests assess severity and prognosis.
Язык: Английский
Процитировано
59
Obesity Facts, Год журнала: 2024, Номер 17(4), С. 374 - 444
Опубликована: Янв. 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.
Язык: Английский
Процитировано
56
Alimentary Pharmacology & Therapeutics, Год журнала: 2023, Номер 59(2), С. 150 - 156
Опубликована: Дек. 28, 2023
The American and European liver associations have endorsed new nomenclature of steatotic disease (SLD) definition metabolic dysfunction-associated (MASLD).
Язык: Английский
Процитировано
49
Drug Discovery Today, Год журнала: 2024, Номер 29(3), С. 103910 - 103910
Опубликована: Фев. 1, 2024
Язык: Английский
Процитировано
49
Clinical and Molecular Hepatology, Год журнала: 2024, Номер unknown
Опубликована: Авг. 19, 2024
As the rates of obesity and type 2 diabetes (T2D) continue to increase globally, so does prevalence metabolic dysfunction associated steatotic liver disease (MASLD). Currently, 38% all adults 7-14% children adolescents have MASLD. By 2040, MASLD rate for is projected over 55%. Although many with will not develop progressive disease, given vast number patients MASLD, it has now become top indication transplant in United States those hepatocellular carcinoma (HCC) women. However, most common cause mortality among remains death cardiovascular diseases. In addition outcomes (cirrhosis HCC), increased risk developing de-novo T2D, chronic kidney sarcopenia extrahepatic cancers. Furthermore, decreased health related quality life, work productivity, fatigue healthcare resource utilization substantial economic burden. Similar other lifestyle interventions heathy diet physical activity remain cornerstone managing these patients. a T2D drugs are available treat co-morbid Resmetirom only MASH-targeted medication that was recently approved by Federal Drug Administration use stage 2-3 fibrosis. The following review provides an overview epidemiology, its factors demonstrates without further global initiatives, may increase.
Язык: Английский
Процитировано
44
Egyptian Liver Journal, Год журнала: 2024, Номер 14(1)
Опубликована: Янв. 2, 2024
Abstract Background Hepatocellular carcinoma (HCC) is a common type of liver cancer, with high mortality rate. cancer that can be effectively managed through early detection and accurate diagnosis, followed by personalized treatment plan may include surgical resection, transplantation, minimally-invasive techniques, immunotherapy, or targeted therapy depending on the stage severity cancer. Main body abstract This paper discusses recent advances in detection, management, prevention HCC. The use newer imaging such as Magnetic resonance (MRI) contrast-enhanced ultrasound, along image segmentation technology deep learning models, have greatly enhanced accuracy HCC diagnosis. Minimally-invasive thermal ablation radiofrequency ablation, allowed for more precise destruction tumors, while Nanoparticles, immunotherapy shown promise management advanced Artificial intelligence (AI) machine has revolutionized research, aiding identification high-risk patients predicting outcomes. Lifestyle modifications, weight alcohol avoidance, hepatitis B vaccinations, play critical role preventing development. Short conclusion Recent improving patient therapy, AI research lifestyle modifications prevention. However, further required to fully understand potential benefits nanoparticles, traditional Chinese medicine herbal medicines treatment. Graphical
Язык: Английский
Процитировано
34