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Maternal High-Fat Diet Reduces Hepatic CoQ in Newborn Rats.
IF 2.6 4区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-04-02 DOI: 10.1016/j.clinre.2025.102592
Francisco Baez, Damian Soria, Mario Contin, Carolina Caniffi, Valeria Tripodi
{"title":"Maternal High-Fat Diet Reduces Hepatic CoQ in Newborn Rats.","authors":"Francisco Baez, Damian Soria, Mario Contin, Carolina Caniffi, Valeria Tripodi","doi":"10.1016/j.clinre.2025.102592","DOIUrl":"https://doi.org/10.1016/j.clinre.2025.102592","url":null,"abstract":"","PeriodicalId":10424,"journal":{"name":"Clinics and research in hepatology and gastroenterology","volume":" ","pages":"102592"},"PeriodicalIF":2.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788039","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}
引用次数: 0
Kala-azar in solid organ transplant recipients, a case report and literature review. Ancient disease, old world, new patients
IF 2.6 4区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-04-01 DOI: 10.1016/j.clinre.2025.102594
Amélie Bouvier , Meja Rabodonirina , Damien Dupont , Valérie Hervieu , Teresa Antonini , Domitille Erard , Christophe Ravel , Marie Simon , Florence Ader , Jérôme Dumortier
{"title":"Kala-azar in solid organ transplant recipients, a case report and literature review. Ancient disease, old world, new patients","authors":"Amélie Bouvier , Meja Rabodonirina , Damien Dupont , Valérie Hervieu , Teresa Antonini , Domitille Erard , Christophe Ravel , Marie Simon , Florence Ader , Jérôme Dumortier","doi":"10.1016/j.clinre.2025.102594","DOIUrl":"10.1016/j.clinre.2025.102594","url":null,"abstract":"","PeriodicalId":10424,"journal":{"name":"Clinics and research in hepatology and gastroenterology","volume":"49 5","pages":"Article 102594"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779330","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}
引用次数: 0
Correlation between non-alcoholic Steatohepatitis and Hepatocellular carcinoma in patients in a Rural State
IF 2.6 4区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-03-31 DOI: 10.1016/j.clinre.2025.102593
Camron Collins , Daniel Conde , Shawn Howell , Samantha Robinson , Hanna Jensen
{"title":"Correlation between non-alcoholic Steatohepatitis and Hepatocellular carcinoma in patients in a Rural State","authors":"Camron Collins , Daniel Conde , Shawn Howell , Samantha Robinson , Hanna Jensen","doi":"10.1016/j.clinre.2025.102593","DOIUrl":"10.1016/j.clinre.2025.102593","url":null,"abstract":"","PeriodicalId":10424,"journal":{"name":"Clinics and research in hepatology and gastroenterology","volume":"49 5","pages":"Article 102593"},"PeriodicalIF":2.6,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143767722","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}
引用次数: 0
Research progress on the regulatory role of different cell death pathways in metabolic-dysfunction-associated steatotic liver disease
IF 2.6 4区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-03-31 DOI: 10.1016/j.clinre.2025.102578
Congyue Zhang , Mengjiao Sun , Yuanjian Ding , Xiwei Yuan , Jingyi Lu , Yuemin Nan
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.
{"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}
引用次数: 0
Emergent endoscopy is associated with lower mortality in hemodynamically unstable upper GI bleeding: single-center experience with 24/7 endoscopy services.
IF 2.6 4区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-03-31 DOI: 10.1016/j.clinre.2025.102580
Thuan Thi-Minh Pham, Duc Trong Quach, Ly Thi-Kim Le, Vy Ngoc-Tuong Nguyen, Ngoc My Chung, Linh Xuan Tran, Quang Dinh Le, Cong Hong-Minh Vo

Background and aims: The effectiveness of emergent endoscopy (EE), defined as endoscopy performed within six hours of admission, for improving outcomes in patients presenting with acute upper gastrointestinal bleeding (AUGIB) remains controversial. This study aimed to evaluate the impact of EE on 42-day rebleeding and mortality rates and identify subgroups of patients who benefit most from this approach.

Methods: We conducted a retrospective cohort study at a tertiary hospital with 24/7 endoscopy services. Eligible patients were aged ≥18 years, presented with AUGIB, and underwent endoscopy within 24 hours of admission. The exclusion criteria included prior interventions at other facilities, in-hospital bleeding for unrelated reasons, or loss to follow-up. All patients were managed under a standardized AUGIB protocol. The primary outcomes were 42-day rebleeding and mortality. The data were analysed via multivariate logistic regression and interaction analyses.

Results: There were 651 patients with a median age of 58.6 years (18-92). The median time from admission to endoscopy was 4.8 hours (3.1-8.0). The 42-day rebleeding and mortality rates were 16.7% and 11.8%, respectively. EE was significantly associated with 42-day mortality but not rebleeding. Independent risk factors for mortality included hemodynamic instability, malignancy, NSAID use, and elevated serum creatinine. Interaction analysis revealed that EE was associated with reduced 42-day mortality in hemodynamically unstable patients (OR: 0.29, 95% CI: 0.145-0.579), a benefit not observed in patients with other risk factors for mortality.

Conclusion: EE appears to be associated with reduced 42-day mortality in patients presenting with hemodynamically unstable AUGIB.

{"title":"Emergent endoscopy is associated with lower mortality in hemodynamically unstable upper GI bleeding: single-center experience with 24/7 endoscopy services.","authors":"Thuan Thi-Minh Pham, Duc Trong Quach, Ly Thi-Kim Le, Vy Ngoc-Tuong Nguyen, Ngoc My Chung, Linh Xuan Tran, Quang Dinh Le, Cong Hong-Minh Vo","doi":"10.1016/j.clinre.2025.102580","DOIUrl":"https://doi.org/10.1016/j.clinre.2025.102580","url":null,"abstract":"<p><strong>Background and aims: </strong>The effectiveness of emergent endoscopy (EE), defined as endoscopy performed within six hours of admission, for improving outcomes in patients presenting with acute upper gastrointestinal bleeding (AUGIB) remains controversial. This study aimed to evaluate the impact of EE on 42-day rebleeding and mortality rates and identify subgroups of patients who benefit most from this approach.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study at a tertiary hospital with 24/7 endoscopy services. Eligible patients were aged ≥18 years, presented with AUGIB, and underwent endoscopy within 24 hours of admission. The exclusion criteria included prior interventions at other facilities, in-hospital bleeding for unrelated reasons, or loss to follow-up. All patients were managed under a standardized AUGIB protocol. The primary outcomes were 42-day rebleeding and mortality. The data were analysed via multivariate logistic regression and interaction analyses.</p><p><strong>Results: </strong>There were 651 patients with a median age of 58.6 years (18-92). The median time from admission to endoscopy was 4.8 hours (3.1-8.0). The 42-day rebleeding and mortality rates were 16.7% and 11.8%, respectively. EE was significantly associated with 42-day mortality but not rebleeding. Independent risk factors for mortality included hemodynamic instability, malignancy, NSAID use, and elevated serum creatinine. Interaction analysis revealed that EE was associated with reduced 42-day mortality in hemodynamically unstable patients (OR: 0.29, 95% CI: 0.145-0.579), a benefit not observed in patients with other risk factors for mortality.</p><p><strong>Conclusion: </strong>EE appears to be associated with reduced 42-day mortality in patients presenting with hemodynamically unstable AUGIB.</p>","PeriodicalId":10424,"journal":{"name":"Clinics and research in hepatology and gastroenterology","volume":" ","pages":"102580"},"PeriodicalIF":2.6,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771538","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}
引用次数: 0
BEND3 promotes hepatocellular carcinoma progression and metastasis by activating the PI3K/AKT/mTOR pathway and inducing epithelial-mesenchymal transition.
IF 2.6 4区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-03-28 DOI: 10.1016/j.clinre.2025.102582
Liu-Lin Yang, Xing Chen, Kai-Ting Huang, Shao-Tong Tang, Gui-Yan Ye, Ji-Long Wang

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

{"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}
引用次数: 0
Relative dose intensity of gemcitabine-nab-paclitaxel combination as second-line or more in locally advanced or metastatic pancreatic adenocarcinoma
IF 2.6 4区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-03-28 DOI: 10.1016/j.clinre.2025.102583
Adrien Grancher , Leila Tagemouati , André Gillibert , Lilian Schwarz , Virginie Vernon , David Sefrioui , Pierre Michel , Marie Dutherage , Frédéric Di Fiore

Background

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.

Aim

To assess the impact of the RDI of GNP as second-line or greater therapy (L2+) for a/mPA.

Methods

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 %.

Results

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<70 % and ≥70 %, with median of 7.0 and 8.1 months (adjusted HR = 1.35; CI95 % [0.89–2.05]; p = 0.2) and 3.1 vs 3.4 months (adjusted HR = 1.36; CI95 % [0.91–2.05]; p = 0.14), respectively. Grade ≥3 toxicities were more common in RDI <70 % as compared to RDI ≥70 % (56.9 % vs. 37.9 %, p = 0.04) and responsible for more GNP dose reductions (67.7 % vs. 50 %, p = 0.13) and schedule modifications (72.4 % vs. 48.2 %, p = 0.008).

Conclusion

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.
{"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}
引用次数: 0
Metabolic dysfunction-associated steatotic liver disease (MASLD): Exploring systemic impacts and innovative therapies 代谢功能障碍相关性脂肪肝(MASLD):探索系统性影响和创新疗法。
IF 2.6 4区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-03-27 DOI: 10.1016/j.clinre.2025.102584
Parag Jain , Akanksha Jain , Rohitas Deshmukh , Pradeep Samal , Trilochan Satapathy , Ajazuddin
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.
{"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}
引用次数: 0
Use of Hepatoscope 2DTE for non-invasive assessment of liver stiffness among Mexican immigrant adults in a community-based setting 在社区环境中使用 Hepatoscope 2DTE 对墨西哥成年移民的肝脏硬度进行无创评估。
IF 2.6 4区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-03-26 DOI: 10.1016/j.clinre.2025.102581
Edgar A. Villavicencio , Cindy Serdjebi , Adriana Maldonado , Estefania Ochoa Mora , Adrien Besson , Naim Alkhouri , David O. Garcia

Purpose

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™.

Methods

Participants (n = 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. LSM2DTE and LSMVCTE 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.

Results

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 (r = 0.53, p < 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.

Conclusion

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.
{"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<sub>2DTE</sub> and LSM<sub>VCTE</sub> 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}
引用次数: 0
Efficacy and safety of aldafermin for the treatment of metabolic dysfunction-associated steatohepatitis: A systematic review and meta-analysis
IF 2.6 4区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-03-25 DOI: 10.1016/j.clinre.2025.102579
Samira Mohamad Khalil , Matheus Henrique Gonçalves de Souza , Fabiana Dolovitsch de Oliveira , Emmily Daiane Buarque de Santana Sato , Gilmara Coelho Meine

Background

We aimed to assess the efficacy and safety of Aldafermin in treating patients with biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH).

Methods

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.

Results

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.

Conclusion

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.
背景我们旨在评估阿尔达非明治疗活检证实的代谢功能障碍相关性脂肪性肝炎(MASH)患者的疗效和安全性:我们检索了PubMed、Embase和Cochrane图书馆截至2024年12月8日的随机对照试验(RCT),这些试验对Aldafermin和安慰剂治疗MASH患者进行了比较。采用随机效应模型对二元结局的风险比 (RR) 和 95% 置信区间 (CI) 进行了汇总。此外,我们还按纤维化分期和阿尔达非明剂量进行了亚组分析,并假设阿尔达非明剂量为协变量进行了元回归分析:结果:我们纳入了 4 项 RCT,涉及 491 名患者。与安慰剂相比,Aldafermin具有更高的MASH缓解而纤维化不恶化的概率(RR 3.04;95%CI 1.12-8.28)、纤维化改善和MASH缓解的复合概率(RR 5.86;95%CI 1.15-29.94)以及通过MRI-PDFF使肝脏脂肪分数减少≥30%的概率(RR 3.14;95%CI 1.44-6.85)。在纤维化改善≥1期且MASH不恶化(RR 1.48;95%CI 0.93-2.35)和总体AEs(RR 1.02;95%CI 0.95-1.11)方面,两组间无明显差异。按纤维化分期和Aldafermin剂量进行的亚组分析显示出一致的结果,按剂量进行的元回归分析显示,MRI-PDFF显示肝脏脂肪分数减少≥30%的结果具有剂量依赖性:总之,与安慰剂相比,Aldafermin能改善MASH的缓解而不加重纤维化,提高纤维化改善和MASH缓解的综合效果,通过MRI-PDFF降低肝脏脂肪率,并且治疗活检证实的MASH患者是安全的。
{"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}
引用次数: 0
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Clinics and research in hepatology and gastroenterology
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