npj Gut and Liver最新文献

{"title":"Scores to predict steatotic liver disease - correlates and outcomes in older adults.","authors":"Daniel Clayton-Chubb, Isabella Commins, Stuart K Roberts, Ammar Majeed, Robyn L Woods, Joanne Ryan, Hans G Schneider, John S Lubel, Alexander D Hodge, John J McNeil, William W Kemp","doi":"10.1038/s44355-025-00021-3","DOIUrl":"https://doi.org/10.1038/s44355-025-00021-3","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant cause of chronic liver disease globally, and the rising prevalence of MASLD is occurring in parallel with the global aging population. The use of non-invasive biomarker tools to rule-in or rule-out hepatic steatosis is important in large epidemiological studies in this field. While the Fatty Liver Index (FLI) is the best validated tool in older adults, not all studies will have the necessary parameters for steatosis identification. This retrospective post-hoc analysis of the ASPirin in Reducing Events in the Elderly (ASPREE) study involved 16,703 Australian adults aged ≥70 years. Using the FLI as the 'gold standard' index, we evaluated the correlation with other indices: the Dallas Steatosis Index (DSI), Framingham Steatosis Index, ZJU index (ZJU), Hepatic Steatosis Index (HSI), Lipid Accumulation Product (LAP), and Visceral Adiposity Index (VAI), as well as age- and sex-adjusted outcome measures including mortality, major adverse cardiovascular events (MACE), atrial fibrillation (AF), and persistent physical disability. Of the non-FLI indices, the DSI and FSI had the highest percentage of participants correctly classified as having MASLD (97.7% and 93.8% respectively). The FSI, LAP, and VAI were associated with MACE. The FSI and FLI were predictive of incident AF. The FLI, DSI, FSI, LAP and VAI were associated with physical disability. No MASLD score was associated with increased mortality. Indeed, MASLD defined by the ZJU and HSI were both inversely associated with mortality. As such, we've demonstrated that the FSI and DSI are the most accurate scores for identifying MASLD in older adults when compared to the FLI as the gold standard. The FSI is associated with MACE, AF, and persistent physical disability, lending support to its use in identifying older persons with MASLD when the FLI is unable to be calculated.</p>","PeriodicalId":501708,"journal":{"name":"npj Gut and Liver","volume":"2 1","pages":"9"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12009214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061434","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":"Steatotic liver disease is a marker of multimorbidity, not underlying cirrhosis, in older adults.","authors":"O Oduwole, C Ding, N Bitar, D Nair, S Salter, M Silverman, R Allen, L Ng Fat, E Tsochatzis, S Bell, G Mehta, A Britton","doi":"10.1038/s44355-025-00024-0","DOIUrl":"https://doi.org/10.1038/s44355-025-00024-0","url":null,"abstract":"<p><p>Steatotic liver disease (SLD) prevalence in adults is estimated at 30%, but older populations are understudied. Here, SLD prevalence and associated risk factors were assessed 1,021 Whitehall II study participants (mean age 72.5) using transient elastography (FibroScan). SLD was present in 33.3% (CAP ≥ 275 dB/m), with most classified as metabolic dysfunction-associated SLD. Only 2.4% had significant fibrosis ( ≥ 7.9 kPa). Adjusted for age and sex, SLD was associated with low physical activity (OR 1.60, 95% CI 1.13-2.27), poorer motor function (SF-36 PCS OR 1.21, 95% CI 1.05-1.40), difficulties in activities of daily living (OR 3.19, 95% CI 1.17-8.64), and multimorbidity (OR 1.45, 95% CI 1.22-1.73). These associations persisted after adjustment for socioeconomic, behavioural, and cardiometabolic risk factors. Frailty was associated with SLD at higher CAP thresholds ( ≥ 290 dB/m). In this older adult sample, SLD is common and appears more as a marker of multimorbidity and low physical activity than significant fibrosis.</p>","PeriodicalId":501708,"journal":{"name":"npj Gut and Liver","volume":"2 1","pages":"10"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061038","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":"Gut microbiota and dynamics of ammonia metabolism in liver disease","authors":"Deepika Jakhar,&nbsp;Shiv K. Sarin,&nbsp;Savneet Kaur","doi":"10.1038/s44355-024-00011-x","DOIUrl":"10.1038/s44355-024-00011-x","url":null,"abstract":"Blood ammonia levels in healthy individuals are low, but they increase in liver disease due to loss of functional liver mass and portosystemic shunting. Hyperammonemia is one of the key factors involved in the prognosis of cirrhosis and its complications. Here we review to establish a connection between alterations in gut microbial communities and intestinal ammonia metabolism, highlighting a key impact of gut dysbiosis on blood ammonia levels during liver disease.","PeriodicalId":501708,"journal":{"name":"npj Gut and Liver","volume":" ","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44355-024-00011-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142762906","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":"Role of VEGFA in type 2 diabetes mellitus rats subjected to partial hepatectomy","authors":"Carlos Rojano-Alfonso,&nbsp;Marc Micó-Carnero,&nbsp;Cristina Maroto-Serrat,&nbsp;Araní Casillas-Ramírez,&nbsp;Carmen Peralta","doi":"10.1038/s44355-024-00013-9","DOIUrl":"10.1038/s44355-024-00013-9","url":null,"abstract":"The crucial role of vascular endothelial growth Factor A (VEGFA) in healthy rat livers undergoing partial hepatectomy under vascular occlusion (PH + I/R) has been demonstrated. This study evaluates whether this observation can be extrapolated to the presence of type 2 diabetes mellitus (T2DM). VEGFA was pharmacologically modulated and its effects during liver surgery were evaluated. Exogenous VEGFA exacerbated necrosis, with no changes in inflammation, apoptosis, or regeneration compared to PH + I/R. Endogenous VEGFA inhibition led to damage and inflammation similar to PH + I/R but promoted regeneration via PI3K/AKT. VEGFA did not affect hepatic VEGFB. VEGFB administration increased necrosis without affecting apoptosis or regeneration. Low hepatic VEGFA and VEGFB in PH + I/R may be influenced by intestine and adipose tissue. Detrimental effects of exogenous VEGFA could be due to exacerbated hepatic necrosis, while endogenous VEGFA inhibition improved regeneration via PI3K/AKT. Therefore, endogenous VEGFA inhibition is a protective strategy promoting liver regeneration in PH + I/R with T2DM.","PeriodicalId":501708,"journal":{"name":"npj Gut and Liver","volume":" ","pages":"1-19"},"PeriodicalIF":0.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44355-024-00013-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142762928","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":"Distinct age-related characteristics in patients with irritable bowel syndrome: patient reported outcomes and measures of gut physiology","authors":"Joost P. Algera,&nbsp;Amanda Blomsten,&nbsp;Mahrukh Khadija,&nbsp;Kristin Verbeke,&nbsp;Tim Vanuytsel,&nbsp;Jan Tack,&nbsp;Magnus Simrén,&nbsp;Hans Törnblom","doi":"10.1038/s44355-024-00010-y","DOIUrl":"10.1038/s44355-024-00010-y","url":null,"abstract":"Irritable bowel syndrome (IBS) is common among all ages, but the associations between symptoms, gut physiology, and ageing are poorly understood. We aimed to characterize patients of different age by comparing symptom reports and gut physiology measures. This retrospective cohort study included IBS patients that completed questionnaires (severity of (non-) gastrointestinal and psychological symptoms, quality of life) and gut physiology testing (transit time, rectal sensitivity, anorectal manometry, small bowel permeability). We included 1677 IBS patients (females 74%, mean age 39 ± 14 years). Younger age was associated with more severe symptoms and worse quality of life. Ageing affects the physiologic state of the gut; older patients have slower gut transit and have an altered anorectal function. Exploratory analyses suggest that age-related changes in gut sensorimotor function could partially explain the severity of specific gastrointestinal symptoms. Our results underline that age should be taken into consideration in the management of IBS.","PeriodicalId":501708,"journal":{"name":"npj Gut and Liver","volume":" ","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44355-024-00010-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142579794","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":"The role of Neuregulin-1 in steatotic and non-steatotic liver transplantation from donors after cardiocirculatory death","authors":"Araní Casillas-Ramírez,&nbsp;Cristina Maroto-Serrat,&nbsp;Carlos Rojano-Alfonso,&nbsp;Francisco Sanus,&nbsp;Marc Micó-Carnero,&nbsp;Margalida Cabrer,&nbsp;Hadassa Yuef Martínez-Padrón,&nbsp;Carmen Peralta","doi":"10.1038/s44355-024-00008-6","DOIUrl":"10.1038/s44355-024-00008-6","url":null,"abstract":"Liver grafts from donors after cardiocirculatory death (DCDs) are sometimes not considered for liver transplantation (LT). Plasma Neuregulin-1 (NRG1) is altered in cardiac abnormalities and the liver is one of the most important targets of NRG1. We study the role of NRG1 in DCD LT. Under these conditions, NRG1 was pharmacologically modulated and their pathways were characterized. NRG1 levels were increased in steatotic and non-steatotic grafts from DCDs; NRG1 was derived from adipose tissue. When NRG1 was inhibited, injury and inflammation were exacerbated. The benefits of endogenous NRG1 in DCD grafts were associated with increased hepatic accumulation of adipocyte-derived vascular endothelial growth factor-A (VEGFA). The Id1-Wnt2 signaling pathway was involved in the action mechanisms of endogenous VEGFA. Exogenous NRG1 exacerbated damage and inflammation. Here differential role of NRG1 (endogenous versus exogenous) was demonstrated and VEGFA treatment was proposed as a highly protective strategy in steatotic and non-steatotic DCD LT.","PeriodicalId":501708,"journal":{"name":"npj Gut and Liver","volume":" ","pages":"1-19"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44355-024-00008-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566006","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":"Impact of oxidized low-density lipoprotein on rat liver sinusoidal endothelial cell morphology and function","authors":"Hong Mao,&nbsp;Larissa D. Kruse,&nbsp;Ruomei Li,&nbsp;Ana Oteiza,&nbsp;Eike C. Struck,&nbsp;Jasmin Schürstedt,&nbsp;Wolfgang Hübner,&nbsp;Victoria C. Cogger,&nbsp;David Le Couteur,&nbsp;Deanna L. Wolfson,&nbsp;Thomas Huser,&nbsp;Balpreet Singh Ahluwalia,&nbsp;Cristina Øie,&nbsp;Peter A. G. McCourt","doi":"10.1038/s44355-024-00009-5","DOIUrl":"10.1038/s44355-024-00009-5","url":null,"abstract":"Atherogenesis is associated with elevated plasma levels of oxidized low-density lipoproteins (oxLDL). In vivo, oxLDL causes liver endothelial swelling, and disrupts liver sinusoidal endothelial cell (LSECs) fenestrations. We mapped the nanoscale kinetics of these changes in vitro in isolated rat LSECs challenged with oxLDL and monitored viability with endocytosis and cytotoxicity assays. OxLDL disrupted LSEC ultrastructure – increasing oxLDL concentrations and oxidation levels caused sieve plate loss, fenestration fusion, and gap formation. Importantly, these effects were not uniform across all LSECs. LSECs retained the ability to endocytose ligands irrespective of the presence of oxLDL. However, increasing oxidation levels and concentrations of oxLDL inhibited LSEC mediated degradation of endocytosed ligands. Viability was unaffected by any oxLDL challenge. In conclusion, oxLDL disrupts LSEC ultrastructural morphology in vitro but LSECs remain viable and mostly maintain the scavenging function during oxLDL challenge.","PeriodicalId":501708,"journal":{"name":"npj Gut and Liver","volume":" ","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44355-024-00009-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519187","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":"Stiffness-induced modulation of ERG transcription factor in chronic liver disease","authors":"Sonia-Emilia Selicean,&nbsp;Eric Felli,&nbsp;Cong Wang,&nbsp;Yeldos Nulan,&nbsp;Juan José Lozano,&nbsp;Sergi Guixé-Muntet,&nbsp;Horia Ștefănescu,&nbsp;Jaime Bosch,&nbsp;Annalisa Berzigotti,&nbsp;Jordi Gracia-Sancho","doi":"10.1038/s44355-024-00007-7","DOIUrl":"10.1038/s44355-024-00007-7","url":null,"abstract":"Chronic liver disease (CLD) is characterised by liver sinusoidal endothelial cells (LSECs) dysfunction. Mechanical forces and inflammation are among the leading factors. ETS-related gene (ERG) is an endothelial-specific transcription factor, involved in maintaining cell quiescence and homeostasis. Our study aimed to understand the expression and modulation of ERG in CLD. ERG expression was characterised and correlated to clinical data in human liver cirrhosis at different disease stages. ERG dynamics in response to stiffness and inflammation were investigated in primary healthy and cirrhotic rat LSEC and in human umbilical vein endothelial cells (HUVECs). ERG is markedly downregulated in cirrhosis independently of disease stage or aetiology and its expression is modulated by substrate stiffness in ECs. Inflammation downregulates ERG in cells on physiological stiffness, but not on high stiffness, suggesting a complementary role of inflammation and stiffness in suppressing ERG. This study outlines ERG as an LSEC inflammation and stiffness-responsive transcription factor in cirrhosis.","PeriodicalId":501708,"journal":{"name":"npj Gut and Liver","volume":" ","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44355-024-00007-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142360060","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":"The Microleaks study: 16S community profile and metagenomic shotgun sequencing signatures associated with anastomotic leak","authors":"Emily C. Hoedt,&nbsp;Georgia Carroll,&nbsp;Bree Stephensen,&nbsp;Katie Togher,&nbsp;Mark Morrison,&nbsp;Veral Vishnoi,&nbsp;Samwel Makanyengo,&nbsp;Brian Draganic,&nbsp;Brendan McManus,&nbsp;Louise Clarke,&nbsp;Kalpesh Shah,&nbsp;Stephen R. Smith,&nbsp;Nicholas J. Talley,&nbsp;Simon Keely,&nbsp;Peter Pockney","doi":"10.1038/s44355-024-00006-8","DOIUrl":"10.1038/s44355-024-00006-8","url":null,"abstract":"Anastomotic leaks (AL) are the most severe complications of colorectal surgery. The cause of AL is unclear, but recent studies have implicated the intestinal microbiota in its development. We aimed to determine whether there is an identifiable microbial pattern in the mucosal microbiota associated with AL. A pragmatic series of 162 patients undergoing colorectal resection with anastomosis had swabs taken from the proximal and distal mucosa of the bowel resection immediately after the tissue was excised. DNA was extracted for 16S rRNA amplicon gene sequencing and a subset for metagenomic shotgun sequencing (MGS). The AL rate in the cohort was approximately 15% (25/162). The alpha diversity measures from the intraoperative swabs were all significantly increased for AL, and there were significant differences in the beta diversity measures for AL from both the 16S and MGS datasets. The predictive power of AL was more sensitive when both proximal and distal communities were considered, and the species-level classifier AUC-ROC was stronger for the MGS dataset than for the 16S data (AUC = 0.92 and 0.76, respectively). We also report, for the first time, the functional changes in intraoperative AL microbes and noted an increase in the relative abundance of pathways with fermentation end products. This result was also found in our murine model of anastomoses (n = 20). At the time of surgery, the mucosal microbiota of the anastomotic extremities exhibits subtle differences at the species level and altered fermentation capacity, which may be associated with AL outcomes. A greater understanding of these insights could improve AL prognosis and preoperative management to reduce the occurrence of this life-threatening condition.","PeriodicalId":501708,"journal":{"name":"npj Gut and Liver","volume":" ","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44355-024-00006-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142117970","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":"Patients with ulcerative colitis who have normalized histology are clinically stable after de-escalation of therapy","authors":"Shintaro Akiyama,&nbsp;Joëlle St-Pierre,&nbsp;Cindy Traboulsi,&nbsp;Alexa Silfen,&nbsp;Victoria Rai,&nbsp;Tina G. Rodriguez,&nbsp;Amarachi I. Erondu,&nbsp;Joshua M. Steinberg,&nbsp;Seth R. Shaffer,&nbsp;Britt Christensen,&nbsp;David T. Rubin","doi":"10.1038/s44355-024-00005-9","DOIUrl":"10.1038/s44355-024-00005-9","url":null,"abstract":"We have previously demonstrated that histological normalization in ulcerative colitis (UC) is associated with superior maintenance of remission outcomes. This single-center, retrospective case-control study assessed outcomes after the therapeutic de-escalation in UC patients who have achieved histologic normalization. A total of 111 patients were included, of which 24 underwent de-escalation, and 87 patients without therapeutic changes. The most commonly withdrawn therapy was aminosalicylates (50%), followed by immunomodulators (37.5%), and biologics (12.5%). Fourteen patients remained on therapies after de-escalation, including aminosalicylate (9/14), immunomodulators (3/14), and biologics (3/14), while 10 patients were not on any therapy immediately after withdrawal. Median follow-up was 43 months in the de-escalation group and 47 months in the control. The rates of clinical, endoscopic, and histologic recurrence were not significantly different between the two groups, nor was the proportion of patients who subsequently required additional therapies after withdrawal (P = 0.133). Clinical and endo-histologic recurrence rates were the lowest in patients who withdrew immunomodulators (0% and 14.3%, respectively). We demonstrate the clinical stability of therapeutic withdrawal in UC patients with histologic normalization.","PeriodicalId":501708,"journal":{"name":"npj Gut and Liver","volume":" ","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44355-024-00005-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141968461","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}