Clinics and research in hepatology and gastroenterology最新文献

{"title":"Research progress on the regulatory role of different cell death pathways in metabolic-dysfunction-associated steatotic liver disease","authors":"Congyue Zhang ,&nbsp;Mengjiao Sun ,&nbsp;Yuanjian Ding ,&nbsp;Xiwei Yuan ,&nbsp;Jingyi Lu ,&nbsp;Yuemin Nan","doi":"10.1016/j.clinre.2025.102578","DOIUrl":"10.1016/j.clinre.2025.102578","url":null,"abstract":"<div><div>Metabolic dysfunction associated steatotic liver disease (MASLD) is one of the most common chronic liver diseases that pose a significant threat to human health. An essential process in developing various diseases, including MASLD, is programmed cell death, a regulated and controlled mechanism that eliminates damaged or unnecessary cells. It is a ubiquitous process during organismal development and represents an active, orderly form of cell death. Significant progress has been made in studying programmed cell death in the context of MASLD. This review systematically summarizes various forms of cell death, including apoptosis, Pyroptosis, autophagy, ferroptosis, and cuproptosis, along with their regulatory mechanisms in MASLD. It has been observed that there are interactions between different forms of cell death. As MASLD progresses through inflammation, fibrosis, and cirrhosis stages, multiple forms of cell death may act synergistically. This article aims to provide the latest research findings and theoretical insights to further our understanding of the pathogenesis of MASLD.</div></div>","PeriodicalId":10424,"journal":{"name":"Clinics and research in hepatology and gastroenterology","volume":"49 6","pages":"Article 102578"},"PeriodicalIF":2.6,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143761321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BEND3 promotes hepatocellular carcinoma progression and metastasis by activating the PI3K/AKT/mTOR pathway and inducing epithelial-mesenchymal transition.","authors":"Liu-Lin Yang, Xing Chen, Kai-Ting Huang, Shao-Tong Tang, Gui-Yan Ye, Ji-Long Wang","doi":"10.1016/j.clinre.2025.102582","DOIUrl":"https://doi.org/10.1016/j.clinre.2025.102582","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the expression of BEND3 in hepatocellular carcinoma (HCC), its correlation with clinical characteristics, and its functional and mechanistic impacts on HCC progression.</p><p><strong>Methods: </strong>Bioinformatics analyses identified BEND3 as highly expressed in HCC and associated with poor clinical prognosis, which was further validated using qRT-PCR, western blotting and immunohistochemistry. Stable BEND3-overexpressing and silenced cell lines were constructed to evaluate its functional effects. CCK-8 and colony formation assays assessed its influence on cell proliferation, while wound healing and Transwell assays evaluated its role in migration and invasion. WB and immunofluorescence were employed to analyze the effects of BEND3 on epithelial-mesenchymal transition (EMT) and the PI3K/AKT/mTOR signaling pathway.</p><p><strong>Results: </strong>Public database analysis, alongside qRT-PCR, western blotting, and immunohistochemical, confirmed that BEND3 expression is significantly elevated in HCC tissues compared to normal liver tissues and is closely associated with poor prognosis. Functional assays demonstrated that BEND3 promotes HCC cell proliferation, migration, and invasion. Mechanistic studies revealed that BEND3 drives HCC progression by inducing EMT and activating the PI3K/AKT/mTOR signaling pathway.</p><p><strong>Conclusion: </strong>BEND3 is highly expressed in HCC and strongly correlates with poor clinical outcomes. Functional and mechanistic analyses indicate that BEND3 enhances HCC progression by promoting proliferation, migration and invasion via EMT induction and PI3K/AKT/mTOR pathway activation.</p>","PeriodicalId":10424,"journal":{"name":"Clinics and research in hepatology and gastroenterology","volume":" ","pages":"102582"},"PeriodicalIF":2.6,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relative dose intensity of gemcitabine-nab-paclitaxel combination as second-line or more in locally advanced or metastatic pancreatic adenocarcinoma","authors":"Adrien Grancher ,&nbsp;Leila Tagemouati ,&nbsp;André Gillibert ,&nbsp;Lilian Schwarz ,&nbsp;Virginie Vernon ,&nbsp;David Sefrioui ,&nbsp;Pierre Michel ,&nbsp;Marie Dutherage ,&nbsp;Frédéric Di Fiore","doi":"10.1016/j.clinre.2025.102583","DOIUrl":"10.1016/j.clinre.2025.102583","url":null,"abstract":"<div><h3>Background</h3><div>Gemcitabine-nab-paclitaxel (GNP) is widely used in treating advanced or metastatic pancreatic adenocarcinoma (a/mPA), but no data are available regarding its relative dose intensity (RDI) beyond the first line.</div></div><div><h3>Aim</h3><div>To assess the impact of the RDI of GNP as second-line or greater therapy (L2+) for a/mPA.</div></div><div><h3>Methods</h3><div>Patients with a/mPA undergoing L2+ treatment were retrospectively included. The RDI was analysed from the start of GNP to the first CT scan. Overall survival (OS), progression-free survival (PFS) and toxicity were analysed according to the RDI at a predefined threshold of 70 %.</div></div><div><h3>Results</h3><div>A total of 116 patients were included, with a median RDI of 70 % (range, 20 %-114 %). There was no significant difference in OS or PFS between RDI&lt;70 % and ≥70 %, with median of 7.0 and 8.1 months (adjusted HR = 1.35; CI95 % [0.89–2.05]; <em>p</em> = 0.2) and 3.1 vs 3.4 months (adjusted HR = 1.36; CI95 % [0.91–2.05]; <em>p</em> = 0.14), respectively. Grade ≥3 toxicities were more common in RDI &lt;70 % as compared to RDI ≥70 % (56.9 % vs. 37.9 %, <em>p</em> = 0.04) and responsible for more GNP dose reductions (67.7 % vs. 50 %, <em>p</em> = 0.13) and schedule modifications (72.4 % vs. 48.2 %, <em>p</em> = 0.008).</div></div><div><h3>Conclusion</h3><div>Our results suggest that the level of GNP exposure, at a predefined RDI threshold of 70 %, had no significant effect on survival in our patients treated in L2+ for a/mPA. Alternative GNP regimens may be evaluated in patients undergoing L2+ treatment for a/mPA.</div></div>","PeriodicalId":10424,"journal":{"name":"Clinics and research in hepatology and gastroenterology","volume":"49 5","pages":"Article 102583"},"PeriodicalIF":2.6,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic dysfunction-associated steatotic liver disease (MASLD): Exploring systemic impacts and innovative therapies","authors":"Parag Jain ,&nbsp;Akanksha Jain ,&nbsp;Rohitas Deshmukh ,&nbsp;Pradeep Samal ,&nbsp;Trilochan Satapathy ,&nbsp;Ajazuddin","doi":"10.1016/j.clinre.2025.102584","DOIUrl":"10.1016/j.clinre.2025.102584","url":null,"abstract":"<div><div>Metabolic dysfunction-associated steatotic liver disease (MASLD), which includes the inflammatory subtype metabolic dysfunction-associated steatohepatitis, is a prominent cause of chronic liver disease with systemic effects. Insulin resistance, obesity, and dyslipidaemia produce MASLD in over 30 % of adults. It is a global health issue. From MASLD to MASH, hepatic inflammation and fibrosis grow, leading to cirrhosis, hepatocellular cancer, and extrahepatic complications such CVD, CKD, and sarcopenia. Effects of MASLD to MASH are mediated through mechanisms that include inflammation, oxidative stress, dysbiosis, and predisposition through genetic makeup. Advances in diagnostic nomenclature in the past few years have moved the emphasis away from NAFLD to MASLD, focusing on the metabolic etiology and away from the stigma of an alcoholic-related condition. Epidemiological data show a large geographical variability and increasing prevalence in younger populations, particularly in regions with high carbohydrate-rich diets and central adiposity. Lifestyle modification is considered as the main management of MASLD currently. This may include dietary intervention, exercise, and weight loss management. Pharmaceutical management is primarily aimed at metabolic dysfunction with promising findings for GLP-1 receptor agonists, pioglitazone and SGLT-2 inhibitors, which can correct both hepatic and systemic outcome. However, it still depends on well-integrated multidisciplinary care models by considering complex relationships between MASLD and its effects on extrahepatic organs. Determining complications at an early stage; developing precision medicine strategies; exploring new therapeutic targets will represent crucial factors in improving their outcomes. This review discuss the systemic nature of MASLD and calls for multiple collaborations to reduce its far-reaching health impacts and our quest for understanding its pathological mechanisms. Thus, collective efforts that are required to address MASLD are under the public health, clinical care, and research angles toward effectively containing its rapidly increasing burden.</div></div>","PeriodicalId":10424,"journal":{"name":"Clinics and research in hepatology and gastroenterology","volume":"49 6","pages":"Article 102584"},"PeriodicalIF":2.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of Hepatoscope 2DTE for non-invasive assessment of liver stiffness among Mexican immigrant adults in a community-based setting","authors":"Edgar A. Villavicencio ,&nbsp;Cindy Serdjebi ,&nbsp;Adriana Maldonado ,&nbsp;Estefania Ochoa Mora ,&nbsp;Adrien Besson ,&nbsp;Naim Alkhouri ,&nbsp;David O. Garcia","doi":"10.1016/j.clinre.2025.102581","DOIUrl":"10.1016/j.clinre.2025.102581","url":null,"abstract":"<div><h3>Purpose</h3><div>Mexican-origin adults have one of the highest rates of metabolic dysfunction-associated steatotic liver disease (MASLD) and its severe form metabolic dysfunction steatohepatitis (MASH) in the US. Given the costs and invasiveness of liver biopsy, this study assessed the application of Hepatoscope® 2DTE, the latest-generation transient elastography for liver stiffness in Mexican adult immigrants from Southern Arizona and compared it with FibroScan® VCTE™.</div></div><div><h3>Methods</h3><div>Participants (<em>n</em> = 199) from a cross-sectional community-based study completed anthropometric measures, demographic information, a blood draw, and liver stiffness measurements (LSM) with FibroScan VCTE and the ultraportable Hepatoscope 2DTE. LSM_2DTE and LSM_VCTE were compared using Spearman's correlation and Bland-Altman analysis. The number of at-risk for fibrosis participants as assessed using each system was compared according to FIB-4.</div></div><div><h3>Results</h3><div>A total of 122 participants were considered for this sub-analysis which consisted of 71.3 % women. Mean age was 51.9 ± 12.1 years, BMI was 30.7 ± 5.7 kg/m², 43.4 % of participants had obesity, and 19.7 % were diabetic. Mean FIB-4 was 1.00 ± 0.53, and median LSM were 5.6 [4.7 - 6.7] and 5.3 [4.1 - 5.8] kPa for 2DTE and VCTE, respectively. 2DTE significantly correlated with VCTE (<em>r</em> = 0.53, <em>p</em> &lt; 0.0001) and there was no systematic bias between the two LSM. There was no difference in the number of at-risk for fibrosis participants between the two LSM per FIB-4 categories.</div></div><div><h3>Conclusion</h3><div>Hepatoscope can be used for point-of-care liver stiffness assessment and risk stratification of adults at risk of liver fibrosis in community-based settings.</div></div>","PeriodicalId":10424,"journal":{"name":"Clinics and research in hepatology and gastroenterology","volume":"49 5","pages":"Article 102581"},"PeriodicalIF":2.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of aldafermin for the treatment of metabolic dysfunction-associated steatohepatitis: A systematic review and meta-analysis","authors":"Samira Mohamad Khalil ,&nbsp;Matheus Henrique Gonçalves de Souza ,&nbsp;Fabiana Dolovitsch de Oliveira ,&nbsp;Emmily Daiane Buarque de Santana Sato ,&nbsp;Gilmara Coelho Meine","doi":"10.1016/j.clinre.2025.102579","DOIUrl":"10.1016/j.clinre.2025.102579","url":null,"abstract":"<div><h3>Background</h3><div>We aimed to assess the efficacy and safety of Aldafermin in treating patients with biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH).</div></div><div><h3>Methods</h3><div>We searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs) comparing Aldafermin to placebo for treating patients with MASH up to December 8, 2024. The risk ratios (RR) with 95 % confidence intervals (CI) were pooled for binary outcomes using a random-effects model. Additionally, we conducted subgroup analysis by fibrosis stage and Aldafermin dosage, and meta-regression analysis assuming the dosage of Aldafermin as a covariate.</div></div><div><h3>Results</h3><div>We included 4 RCTs, encompassing 491 patients. Compared to placebo, Aldafermin had a higher probability of MASH resolution without worsening of fibrosis (RR 3.04; 95 %CI 1.12–8.28), composite of fibrosis improvement and MASH resolution (RR 5.86; 95 %CI 1.15–29.94), and reduction ≥30 % in hepatic fat fraction by MRI-PDFF (RR 3.14; 95 %CI 1.44–6.85). There were no significant differences in fibrosis improvement ≥1 stage without worsening of MASH (RR 1.48; 95 %CI 0.93–2.35), and overall AEs (RR 1.02; 95 %CI 0.95–1.11) between the groups. Subgroup analysis by fibrosis stage and Aldafermin dosage showed consistent results, and meta-regression analysis by dosage showed a dose-dependent improvement for the outcome of ≥30 % reduction in hepatic fat fraction by MRI-PDFF.</div></div><div><h3>Conclusion</h3><div>In conclusion, Aldafermin improved MASH resolution without worsening fibrosis, enhanced the composite of fibrosis improvement and MASH resolution, reduced hepatic fat fraction by MRI-PDFF, and was safe for treating patients with biopsy-confirmed MASH compared to placebo.</div></div>","PeriodicalId":10424,"journal":{"name":"Clinics and research in hepatology and gastroenterology","volume":"49 5","pages":"Article 102579"},"PeriodicalIF":2.6,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anal incontinence in adults under 65 years: A survey based on social networks","authors":"Aurélien Venara ,&nbsp;Mathieu Levaillant ,&nbsp;Maëlig Poitevin ,&nbsp;Véronique Vitton ,&nbsp;Jean-Francois Hamel","doi":"10.1016/j.clinre.2025.102577","DOIUrl":"10.1016/j.clinre.2025.102577","url":null,"abstract":"<div><h3>Introduction</h3><div>The frequency of anal incontinence in the general population is likely an underestimation, particularly among adults ≤65 years, for whom personal and professional considerations limit their utilization of medical care. The objective of this study was to assess the prevalence of anal incontinence in the young population and to address the reasons why such individuals do not seek care.</div></div><div><h3>Methods</h3><div>This was a public health survey conducted using personal and professional social networks between April and November 2023. Participants between the ages of 18 and 65 were invited to respond a survey about their experience of anal incontinence (AI). The survey collected data on the Vaizey's score and the Anal Incontinence Quality of Life Index (FIQL).</div></div><div><h3>Results</h3><div>Of the 481 individuals who completed the survey, 176 (36.6 %) reported experiencing AI. The majority of respondents exhibited mild incontinence (46 %), while 15.8 % experienced severe or major AI. Among those with AI, only 27.3 % consulted a physician, and in nearly 40 % of cases, no treatment was proposed. The primary reasons for not seeking consultation were embarrassment about the condition (63 %) and perceived stigma surrounding treatment (28 %), including a lack of awareness about available treatments. Multivariate analysis revealed that individuals between the ages of 26 and 45 were more likely to seek medical attention.</div></div><div><h3>Conclusion</h3><div>The prevalence of incontinence of the anal nature among young adults remains significantly underestimated, despite its impact on their quality of life. Enhanced public health communication regarding the management of incontinence, particularly among young individuals and healthcare providers, is imperative.</div></div>","PeriodicalId":10424,"journal":{"name":"Clinics and research in hepatology and gastroenterology","volume":"49 5","pages":"Article 102577"},"PeriodicalIF":2.6,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143685693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-obstructive sinusoidal dilation in inflammatory bowel disease","authors":"Nishali Shah ,&nbsp;Kapil Gupta ,&nbsp;Vinod Rustgi ,&nbsp;Carlos Minacapelli ,&nbsp;Mark Bramwit ,&nbsp;Lea Ann Chen","doi":"10.1016/j.clinre.2025.102576","DOIUrl":"10.1016/j.clinre.2025.102576","url":null,"abstract":"","PeriodicalId":10424,"journal":{"name":"Clinics and research in hepatology and gastroenterology","volume":"49 5","pages":"Article 102576"},"PeriodicalIF":2.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypotransferrinemia leading to fatal hemochromatosis without anemia","authors":"Houda Hamdi-Roze ,&nbsp;Emilie Morandeau ,&nbsp;Martine Ropert-Bouchet ,&nbsp;Lenaick Detivaud ,&nbsp;Christophe Bureau ,&nbsp;Edouard Bardou-Jacquet","doi":"10.1016/j.clinre.2025.102574","DOIUrl":"10.1016/j.clinre.2025.102574","url":null,"abstract":"","PeriodicalId":10424,"journal":{"name":"Clinics and research in hepatology and gastroenterology","volume":"49 4","pages":"Article 102574"},"PeriodicalIF":2.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utilization of the gastroduodenal-type full thickness resection device for completion of resection of a tiny neuroendocrine neoplasia remnant in the rectum","authors":"Vincent Zimmer","doi":"10.1016/j.clinre.2025.102575","DOIUrl":"10.1016/j.clinre.2025.102575","url":null,"abstract":"","PeriodicalId":10424,"journal":{"name":"Clinics and research in hepatology and gastroenterology","volume":"49 5","pages":"Article 102575"},"PeriodicalIF":2.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}