npj Gut and Liver最新文献

{"title":"Resmetirom and GLP-1 agonists for MASH: complementary rather than exclusive","authors":"Xiao-Dong Zhou, Vincent Wai-Sun Wong, Ming-Hua Zheng","doi":"10.1038/s44355-024-00004-w","DOIUrl":"10.1038/s44355-024-00004-w","url":null,"abstract":"Developing drugs for metabolic dysfunction-associated steatohepatitis (MASH) has been a surprisingly challenging task. To effectively treat MASH, the drug should address the three key issues associated with these conditions: fat accumulation, inflammation, and fibrosis. However, no therapeutic drugs have been able to meet all the required criteria, especially when it comes to improving fibrosis. With FDA approval, resmetirom, a liver-targeted thyroid hormone receptor-β (THRβ) selective agonist, changes the MASH drug development landscape. The activation of THRβ is known to improve MASH by controlling fat synthesis, regulating fatty acid oxidation, cholesterol metabolism, mitochondrial function, and reducing inflammation and fibrosis. Glucagon-like peptide-1 (GLP-1) agonists, employed to treat diabetes and obesity, has been tested on MASH patients and is widely regarded as the preferred treatment for MASH. GLP-1 agonists are regarded as the primary contenders for resmetirom. Some even suggest that GLP-1 agonists might have the potential to supplant MASH therapy in its entirety. It should be noted that while GLP-1 agonists positively impact metabolism upstream of the liver, this may not subsequently improve the fibrotic liver injury within the tested treatment duration. Combining the therapeutic approaches of GLP-1 agonists (which target extrahepatic mechanisms for metabolic disorders) with resmetirom (which target intrahepatic mechanisms for MASH and liver fibrosis) seems like a promising strategy for addressing fat accumulation, inflammation, and fibrosis associated with MASH.","PeriodicalId":501708,"journal":{"name":"npj Gut and Liver","volume":" ","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44355-024-00004-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141968460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing the liver transplant candidate","authors":"Christopher Kasia, Andres Duarte-Rojo","doi":"10.1038/s44355-024-00003-x","DOIUrl":"10.1038/s44355-024-00003-x","url":null,"abstract":"The purpose of this review is to highlight common and best practices in liver transplant evaluation and management, particularly on how to best optimize a patient to become a successful recipient. There is an increasing armamentarium of pharmacologic, procedural, and behavioral interventions that has grown in body of evidence and use in clinical practice to best prepare patients for liver transplant. This includes tools in the management of common decompensations in liver disease, such as hepatic encephalopathy or ascites, as well as associated medical comorbidities that are also encountered in the general population. Aside from management of decompensations, a holistic approach to pre-operative care, including prehabilitation, is becoming increasingly more important to improve sarcopenia, frailty, and quality of life through an exercise program and nutritional modifications. Social determinants of health have become an increasingly recognized barrier to equitable LT access and have garnered increasing attention in the last several years. The road to liver transplantation is a multi-disciplinary patient-centered journey. The complications of decompensated disease require thoughtful decision making as it pertains to management and is a careful balance to avoid the creation of iatrogenic complications which can impact clinical stability and candidacy. Further investment in the management of behavioral modifications and lifestyle is an essential part of the treatment process.","PeriodicalId":501708,"journal":{"name":"npj Gut and Liver","volume":" ","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44355-024-00003-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations of the peptidomic composition of peripheral plasma after portal hypertension correction by transjugular intrahepatic portosystemic shunt","authors":"Giulia Ilaria Bagarolo, Shruti Bhargava, Robert Schierwagen, Wenyi Gu, Vera Jankowski, Josefin Soppert, Emona Barzakova, Federica Cascone, Olaf Tyc, Christiane Kuhl, Heidi Noels, Jonel Trebicka, Joachim Jankowski","doi":"10.1038/s44355-024-00001-z","DOIUrl":"10.1038/s44355-024-00001-z","url":null,"abstract":"Portal hypertension develops in patients with advanced chronic liver diseases (CLD), especially cirrhosis and is associated with complications, such as gastrointestinal bleeding and ascites resulting in high mortality. The transjugular intrahepatic portosystemic shunt (TIPS) is a treatment option for portal hypertension, aiming to decrease portal venous pressure by establishing an artificial passage for blood from the gastrointestinal tract to the liver vein. This study focuses on the differences in the molecular composition of plasma samples from patients with portal hypertension before and after TIPS intervention to identify and characterise potential mediators influencing gut-liver cross-talk. The plasma of 23 patients displaying advanced CLD with portal hypertension was collected from peripheral veins before and after TIPS treatment and analysed using a well-established non-targeted chromatography-mass spectrometric (LC-MS) approach. Sialomucin core protein 24(CD164)(160–180), meckelin(99-118), Histone-lysine N-methyltransferase(MLL3)(3019-3045) and transient receptor potential cation channel subfamily V member 5(TRPV5)(614-630) were identified to be downregulated after the TIPS treatment. In addition, the metabolites 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF), uric acid, dopamine, homoarginine, leucylproline and 5-methyluridine were significantly decreased after TIPS, whereas one yet unidentified low molecular-weight metabolite showed an increase after the medical procedure. In conclusion, these substances are novel potential biomarkers for portal hypertension in patients with CLD, with mechanistic clues of involvement in regulating pathological gut-liver cross-talk.","PeriodicalId":501708,"journal":{"name":"npj Gut and Liver","volume":" ","pages":"1-12"},"PeriodicalIF":0.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44355-024-00001-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141298825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accelerometer-based sedentary time and physical activity with MASLD and liver cirrhosis in 2684 British adolescents","authors":"Andrew O. Agbaje","doi":"10.1038/s44355-024-00002-y","DOIUrl":"10.1038/s44355-024-00002-y","url":null,"abstract":"Evidence on the long-term relationship of sedentary time (ST), light physical activity (LPA) and moderate-to-vigorous PA (MVPA) with liver steatosis, fibrosis, cirrhosis, and changes in liver enzymes in the paediatric population is limited. This study examined the associations of cumulative ST, LPA and MVPA from childhood with longitudinal changes in liver indices and enzymes. From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 2684 children aged 11 years who had at least one follow-up time-points accelerometer-measured ST, LPA and MVPA over a period of 13 years, and liver indices and enzymes measures at age 24 years clinic visit were included. Liver steatosis and fibrosis were assessed by transient elastography and staged as fibrosis stage F0-F4 and steatosis grade (S0-S3) at age 24 years. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transferase (GGT) were assayed at ages 17 and 24 years. Longitudinal associations were examined using generalized linear mixed-effect models, while mediation analyses were conducted with structural equation models. Among 2684 children (mean [SD] age, 11.75 [0.24] years; 1537 [57.3%] females]), the prevalence of liver steatosis at age 17 years was 2.6% and 20.5% at age 24 years. The cumulative 1-minute/day increase in ST from ages 11–24 years was associated with higher odds of liver cirrhosis (odds ratio 1.004 [95% CI 1.002–1.005] p < 0.001) and severe liver steatosis (1.001 [1.001–1.002] p = 0.002) at age 24 years. Increased ST from childhood was directly associated with progressively increased ALT, AST and GGT from ages 17 to 24 years. Cumulative 1-min/day LPA was associated with lower odds of liver cirrhosis (0.990 [0.990–0.991] p < 0.001) and severe liver steatosis (0.999 [0.998–0.999] p < 0.001) at age 24 years, as well as decreased liver enzymes. Cumulative 1-min/day MVPA was associated with associated with lower odds of severe liver steatosis (0.996 [0.994–0.998] p < 0.001) but not liver cirrhosis at age 24 years. MVPA effect on lowering liver steatosis was significantly suppressed (64% suppression) by increased fat mass. In conclusion, increasing LPA, sustaining MVPA and decreasing ST from childhood may independently attenuate and reverse the risk of severe liver steatosis and liver cirrhosis by young adulthood.","PeriodicalId":501708,"journal":{"name":"npj Gut and Liver","volume":" ","pages":"1-13"},"PeriodicalIF":0.0,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44355-024-00002-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141165071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}