Hepatology最新文献

{"title":"Letter to the editor : Association of hepatitis delta virus infection and hepatocellular carcinoma, hepatic decompensation, all-cause and liver-related death in a national cohort","authors":"Ziyi He, Chenxi Wang, Huichuan Tian","doi":"10.1097/hep.0000000000001159","DOIUrl":"https://doi.org/10.1097/hep.0000000000001159","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"5 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral LPCN 1148 improves sarcopenia and hepatic encephalopathy in male patients with cirrhosis: A randomized, placebo-controlled phase 2 trial","authors":"Benjamin J. Bruno, Joshua C. Weavil, Jonathan Ogle, Nachiappan Chidambaram, Elizabeth J. Carey, Christopher J. Danford, Zarchary P. Fricker, Joseph S. Galati, William M. Lee, Parvez S. Mantry, Kirti Shetty, Anthony DelConte, Mahesh V. Patel, Jennifer C. Lai, Arun J. Sanyal","doi":"10.1097/hep.0000000000001146","DOIUrl":"https://doi.org/10.1097/hep.0000000000001146","url":null,"abstract":"Background &amp; Aims: Sarcopenia is highly prevalent in patients with liver cirrhosis and is associated with adverse clinical outcomes including hepatic encephalopathy (HE). Androgen receptor agonists, ARAs, can address these conditions through multimodal mechanisms of action, however their safety and efficacy in patients with cirrhosis have not been well established. Approach &amp; Results: In this multicenter, double-blind, phase 2 trial, men with sarcopenia and cirrhosis awaiting liver transplant were randomized 1:1 to receive either oral ARA LPCN 1148 or placebo for 24 weeks (NCT04874350). The primary endpoint was the change from baseline to 24 weeks in skeletal muscle index measured by computed tomography scan of the L3 region (L3-SMI), analyzed with a prespecified modified intent-to-treat population. The secondary endpoint was the number of overt HE events. 29 participants (mean age=59 y, MELD=17) received at least one dose of LPCN 1148 (n=15) or placebo (n=14). Baseline characteristics were similar between groups. Primary endpoint analysis demonstrated an increase in L3-SMI in the LPCN 1148 group (n=15) compared to placebo (n=10), with a mean group difference of 4.4 cm<jats:sup>2</jats:sup>/m<jats:sup>2</jats:sup> (95% CI, 1.3-7.4 cm<jats:sup>2</jats:sup>/m<jats:sup>2</jats:sup>, <jats:italic toggle=\"yes\">p</jats:italic>=0.007). Participants in LPCN 1148 experienced fewer episodes of overt HE (CTCAE grade ≥2; <jats:italic toggle=\"yes\">p</jats:italic>=0.02) than placebo. The number and severity of treatment-emergent adverse events were similar between arms. Conclusions: LPCN 1148 treatment improved sarcopenia and reduced the number of overt HE episodes in men with cirrhosis and sarcopenia awaiting liver transplant. These findings support additional research on the efficacy of LPCN 1148 in treating sarcopenia and preventing HE recurrence.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"33 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelet-derived mitochondria regulate lipid metabolism in nonalcoholic steatohepatitis via extracellular vesicles","authors":"Tsai-Ling Liao, Der-Yuan Chen, Shie-Liang Hsieh, Ying-Ying Yang, Yi-Ming Chen, Kuo-Tung Tang, Chung-Hsin Chang, Sheng-Shun Yang","doi":"10.1097/hep.0000000000001149","DOIUrl":"https://doi.org/10.1097/hep.0000000000001149","url":null,"abstract":"Background &amp; Aims: Immune system activation along with lipotoxicity due to excessive lipid droplet (LD) accumulation in the liver are key drivers of non-alcoholic steatohepatitis (NASH). Extracellular vesicles (EVs) released by cells that carry biological signals to contribute intercellular communication. But the roles of immune cells-derived EVs in pathogenesis of NASH are unclear. Approach &amp; Results: Platelets are abundant in blood. We explored the role of platelet-derived EVs (pEVs) in LD accumulation from 30 patients with non-alcoholic fatty liver disease of different severity as well as 20 healthy subjects, a rat model, and an <jats:italic toggle=\"yes\">in vitro</jats:italic> cell-based assay. There was increased platelet activation, accompanied by pEVs release, in NASH patients/rat model, and palmitate-treated cells. The mitochondria in the platelets and pEVs from NASH patients/rats were increased but dysfunctional, including a reduction in fatty acid β-oxidation, inactivated ACC2, and suppressed oxidative phosphorylation system complex II/III/IV activity. These damaged mitochondria could be transferred to hepatocytes via pEVs to increase the number of lipid droplet–bound mitochondria (LDM). An increase in dysfunctional LDM in hepatocytes affects lipid metabolism, resulting in excessive LD accumulation, elevated mitochondrial ROS production, and apoptosis. Conclusions: We offer a novel molecular mechanism that connects platelets, pEVs, and excessive LD accumulation to the development of NASH. Our results suggest that NASH progression may be alleviated by specifically inhibiting the production and release of pEVs, or by targeting pEVs components and inhibiting their uptake. Additional experiments are required to confirm this potentiality.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"6 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor: Clonally expanded CD8+ T cells in MASH – invited guests overstaying their welcome","authors":"Nicole Hilbert, Georg Lurje, Frank Tacke, Linda Hammerich, Isabella Lurje","doi":"10.1097/hep.0000000000001122","DOIUrl":"https://doi.org/10.1097/hep.0000000000001122","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"148 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hemodynamic effects of carvedilol plus simvastatin in cirrhosis with severe portal hypertension and suboptimal response to β-blockers: A double-blind, placebo-controlled, randomized-trial","authors":"Edilmar Alvarado-Tapias, Anna Brujats, Angela Puente, Alba Ardevol, Ainhoa Rodriguez-Arias, Javier Fajardo, Oanna Pavel, Marta Garcia-Guix, Carles Aracil, Maria Poca, Berta Cuyàs, Elisabet Cantó, Rosa Montañés, Alvaro Garcia-Osuna, Àngels Escorsell, Xavier Torras, Càndid Villanueva","doi":"10.1097/hep.0000000000001148","DOIUrl":"https://doi.org/10.1097/hep.0000000000001148","url":null,"abstract":"Background &amp; Aims: Carvedilol is a non-selective β-blocker (NSBBs) with anti-α1-adrenergic activity, more effective than traditional NSBBs in reducing portal-pressure (HVPG). However, 35%-45% of patients still have insufficient HVPG-decrease. Statins ameliorate endothelial dysfunction, reduce hepatic vascular resistance, and have pleiotropic effects. We investigated whether the addition of simvastatin improves the efficacy of carvedilol on HVPG in cirrhosis with severe portal-hypertension and suboptimal response to traditional-NSBBs. Methods: Patients with cirrhosis and high-risk varices referred for primary prophylaxis were consecutively included. HVPG was measured at baseline and again after i.v.propranolol. Suboptimal responders (HVPG-decrease &lt;20%) were treated with carvedilol and were randomized to double-blind administration of placebo or simvastatin. Chronic HVPG response was assessed after 4-6-weeks, repeating HVPG-measurements after a standard liquid meal to estimate endothelial dysfunction. Plasma samples were obtained before each study to investigate inflammatory parameters. Results: Of 184 eligible patients, 82 were randomized to carvedilol+simvastatin (N=41) or carvedilol+placebo (N=41). Baseline characteristics were similar. HVPG significantly decreased with both, carvedilol+simvastatin (18.6±4-to-15.7±4 mm Hg, <jats:italic toggle=\"yes\">p</jats:italic>&lt;0.001) and carvedilol+placebo (18.9±3-to-16.9±3 mm Hg, <jats:italic toggle=\"yes\">p</jats:italic>&lt;0.001). The decrease was greater with carvedilol+simvastatin (2.97±2.5 vs. 2.05±1.6 mm Hg, <jats:italic toggle=\"yes\">p</jats:italic>=0.031). An HVPG-decrease ≥20% occurred in 37% versus 15% patients respectively (OR:3.37, 95% CI=1.15-9.85; <jats:italic toggle=\"yes\">p</jats:italic>=0.021). With test-meal, HVPG increased in both groups (<jats:italic toggle=\"yes\">p</jats:italic>&lt;0.01), although carvedilol+simvastatin attenuated such increment (12±8% vs. 23±16%, <jats:italic toggle=\"yes\">p</jats:italic>&lt;0.001). Cytokine levels (IL-6,MCP-1,MDA) decreased significantly more with carvedilol+simvastatin (<jats:italic toggle=\"yes\">p</jats:italic>&lt;0.01). Incidence of adverse events was similar. Conclusion: In patients with severe portal hypertension (all with high-risk varices) and suboptimal hemodynamic response to traditional NSBBs, combined therapy with carvedilol plus simvastatin significantly enhances the portal-pressure reduction achieved with carvedilol-monotherapy, improves endothelial dysfunction and reduces pro-inflammatory cytokines.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"45 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply: Enhancing automated speech analysis for hepatic encephalopathy detection","authors":"Patricia P. Bloom, Anna S. Lok","doi":"10.1097/hep.0000000000001151","DOIUrl":"https://doi.org/10.1097/hep.0000000000001151","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"11 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor: Enhancing automated speech analysis for hepatic encephalopathy detection","authors":"Sheng Li, Zhou Wu","doi":"10.1097/hep.0000000000001150","DOIUrl":"https://doi.org/10.1097/hep.0000000000001150","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"244 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liver transplantation for nonstandard oncological indications: Are we there yet?","authors":"Beat Moeckli, Joana Rodrigues Ribeiro, Christian Toso","doi":"10.1097/HEP.0000000000001131","DOIUrl":"https://doi.org/10.1097/HEP.0000000000001131","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":12.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply: Regarding terlipressin-related patient outcomes in hepatorenal syndrome-acute kidney injury.","authors":"Madhumita Premkumar, Anand Kulkarni, Manhal Izzy","doi":"10.1097/HEP.0000000000000988","DOIUrl":"10.1097/HEP.0000000000000988","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"E79-E80"},"PeriodicalIF":12.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141454174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The macrophage STING-YAP axis controls hepatic steatosis by promoting the autophagic degradation of lipid droplets.","authors":"Tao Yang, Xiaoye Qu, Xiao Wang, Dongwei Xu, Mingwei Sheng, Yuanbang Lin, Michael Ke, Ci Song, Qiang Xia, Longfeng Jiang, Jun Li, Douglas G Farmer, Bibo Ke","doi":"10.1097/HEP.0000000000000638","DOIUrl":"10.1097/HEP.0000000000000638","url":null,"abstract":"<p><strong>Background and aims: </strong>The hallmark of NAFLD or hepatic steatosis is characterized by lipid droplet (LD) accumulation in hepatocytes. Autophagy may have profound effects on lipid metabolism and innate immune response. However, how innate immune activation may regulate the autophagic degradation of intracellular LDs remains elusive.</p><p><strong>Approach and results: </strong>A mouse model of a high-fat diet-induced NASH was used in the myeloid-specific stimulator of interferon genes (STING) knockout or STING/yes-associated protein (YAP) double knockout mice. Liver injury, lipid accumulation, lipid droplet proteins, autophagic genes, chromatin immunoprecipitation coupled with massively parallel sequencing, and RNA-Seq were assessed in vivo and in vitro . We found that high-fat diet-induced oxidative stress activates STING and YAP pathways in hepatic macrophages. The acrophage STING deficiency (myeloid-specific STING knockout) enhances nuclear YAP activity, reduces lipid accumulation, and increases autophagy-related proteins ATG5, ATG7, and light chain 3B but diminishes LD protein perilipin 2 expression. However, disruption of STING and YAP (myeloid STING and YAP double knockout) increases serum alanine aminotransferase and triglyceride levels and reduces β-fatty acid oxidation gene expression but augments perilipin 2 levels, exacerbating high-fat diet-induced lipid deposition. Chromatin immunoprecipitation coupled with massively parallel sequencing reveals that macrophage YAP targets transmembrane protein 205 and activates AMP-activated protein kinase α, which interacts with hepatocyte mitofusin 2 and induces protein disulfide isomerase activation. Protein disulfide isomerase activates hypoxia-inducible factor-1α signaling, increases autophagosome colocalization with LDs, and promotes the degradation of perilipin 2 by interacting with chaperone-mediated autophagy chaperone HSC70.</p><p><strong>Conclusions: </strong>The macrophage STING-YAP axis controls hepatic steatosis by reprogramming lipid metabolism in a transmembrane protein 205/mitofusin 2/protein disulfide isomerase-dependent pathway. These findings highlight the regulatory mechanism of the macrophage STING-driven YAP activity on lipid control.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"1169-1183"},"PeriodicalIF":12.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11035483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49687375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}