Annals of hepatology最新文献

{"title":"Mechanisms and therapeutic targets of mitochondria in the progression of metabolic dysfunction-associated steatotic liver disease.","authors":"Chenyang Mu, Sijie Wang, Zenghan Wang, Jian Tan, Haozan Yin, Yuefan Wang, Zhihui Dai, Dongyang Ding, Fu Yang","doi":"10.1016/j.aohep.2024.101774","DOIUrl":"https://doi.org/10.1016/j.aohep.2024.101774","url":null,"abstract":"<p><p>Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) includes liver disease processes from simple fatty liver to nonalcoholic steatohepatitis, which may progress to liver fibrosis, cirrhosis, and even hepatocellular carcinoma (HCC). As the incidence of HCC derived from viral hepatitis decreases, MASLD has emerged as a significant health threat, driven by lifestyle changes and rising obesity rates among patients. The pathogenesis of MASLD is complex, involving factors such as insulin resistance, gut microbiota imbalance, and genetic and epigenetic factors. In recent years, the role of mitochondrial dysfunction in MASLD has gained significant attention, involving β-oxidation imbalance, oxidative stress increase, mitophagy defects, and mitochondrial DNA (mtDNA) mutations. This article reviews the pathophysiological mechanisms of mitochondrial dysfunction in MASLD, diagnostic methods, and potential therapeutic strategies. By synthesizing current research findings, the review aims to highlight the critical role of mitochondrial dysfunction as a target for future diagnostic and therapeutic interventions. This focus could pave the way for innovative clinical strategies, ultimately improving treatment options and patient prognosis in MASLD.</p>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":" ","pages":"101774"},"PeriodicalIF":3.7,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of inflammasomes in hepatocellular carcinoma: Mechanisms and therapeutic insights.","authors":"Valentina Arrè, Roberto Negro, Gianluigi Giannelli","doi":"10.1016/j.aohep.2024.101772","DOIUrl":"https://doi.org/10.1016/j.aohep.2024.101772","url":null,"abstract":"<p><p>Hepatocellular carcinoma is among the most frequent forms of primary liver cancer and develops within a context of chronic inflammation, frequently associated with a multitude of risk factors, including viral infections, metabolic dysfunction-associated fatty liver disease, metabolic dysfunction-associated steatohepatitis and liver fibrosis. The tumor microenvironment is crucial for the progression of HCC, as immune cells, tumor-associated fibroblasts and hepatic stellate cells interact to promote chronic inflammation and tumor spread. Inflammasomes, the multiprotein complexes that launch the innate immune response, emerge as important mediators in the pathogenesis of HCC. Among others, the inflammasome Nucleotide-binding oligomerization domain, Leucine rich Repeat (NLR) and Pyrin (NLRP) 3 (NLRP3), and absent in melanoma 2 (AIM2), exhibit a dual role in HCC background. It has been reported that they can exert oncosuppressive functions by triggering the inflammatory death of cancer cells. Vice versa, chronic activation contributes to the development of a pro-tumorigenic environment, thus supporting tumor growth. In addition, other inflammasomes such as Nucleotide-binding oligomerization domain, Leucine rich Repeat (NLR) and Pyrin (NLRP) 6 and 12 (NLRP6 and NLRP12, respectively) regulate HCC onset and progression, although more experimental evidence is required. This review focuses on the molecular mechanisms underpinning the inflammasome's contribution to the onset, progression and spread of HCC. Moreover, we will explore the potential therapeutic approaches currently under investigation, which aim to improve the efficacy and reduce the side effects of the treatments currently available. Targeting inflammasomes may be a promising therapeutic strategy for the treatment of HCC, offering new opportunities to improve patient prognosis.</p>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":" ","pages":"101772"},"PeriodicalIF":3.7,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of bariatric endoscopy on liver fibrosis and steatosis and the course of NAFLD - a prospective interventional study.","authors":"Adam Vašura, Evžen Machytka, Ondřej Urban, Jitka Macháčková, Lubomír Pavliska, Zdeněk Berka, Zdeněk Švagera, Marek Bužga","doi":"10.1016/j.aohep.2024.101765","DOIUrl":"10.1016/j.aohep.2024.101765","url":null,"abstract":"<p><strong>Introduction and objectives: </strong>With increases in obesity and metabolic syndrome because of lifestyle-related factors, the prevalence of non-alcoholic fatty liver disease (NAFLD) also is increasing worldwide. In a subset of patients with NAFLD, an inflammatory process arises in the steatotic liver, known as non-alcoholic steatohepatitis, that leads to liver fibrosis and liver cirrhosis. In selected patients with obesity, bariatric surgery, and bariatric endoscopy are important therapeutic options.</p><p><strong>Materials and methods: </strong>This prospective interventional pilot study was conducted to investigate two types of intragastric balloons (IGB). The IGBs were the Orbera and the Spatz3. Liver fibrosis changes were monitored non-invasively using point and 2D shear wave ultrasound elastography (SWE) and transient elastography that allowed for quantification of liver steatosis using the controlled attenuation parameter (CAP). Patients were followed for 12 months.</p><p><strong>Results: </strong>Of 34 patients implanted with an IGB, 30 completed follow-up at month 12; results for one patient were excluded because of initiation of obesity pharmacotherapy. Fifteen patients received the Orbera IGB, and nineteen patients received the Spatz3 type. In month 12, total and excess weight loss was 7.88 % and 30.13 %. Elastography values decreased from baseline (3.88 kPa) to 3.61 kPa at month 12 (p 0.024). 2D SWE values decreased from baseline (5.42 kPa) to a value of 4.91 kPa at month twelve (p 0.135). Transient elastography values decreased from baseline (5.62 kPa) to a value of 4.17 kPa at month twelve (p 0.009).</p><p><strong>Conclusions: </strong>Bariatric endoscopy in the form of IGB implantation leads to weight reduction and improvement of liver fibrosis and steatosis.</p><p><strong>Clinicaltrials: </strong></p><p><strong>Gov registration: </strong>NCT04895943.</p>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":" ","pages":"101765"},"PeriodicalIF":3.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An exploratory machine learning model for predicting advanced liver fibrosis in autoimmune hepatitis patients: A preliminary study.","authors":"Qinglin Wei, Wen Li, Shubei He, Hongbo Wu, Qiaoling Xie, Ying Peng, Xingyue Zhang","doi":"10.1016/j.aohep.2024.101754","DOIUrl":"10.1016/j.aohep.2024.101754","url":null,"abstract":"<p><strong>Introduction and objectives: </strong>Advanced fibrosis is a crucial stage in the progression of autoimmune hepatitis (AIH), where fibrosis can either regress or advance. This study aims to leverage machine learning (ML) models for the assessment of advanced liver fibrosis in AIH patients using routine clinical features.</p><p><strong>Patients and methods: </strong>A total of 233 patients diagnosed with AIH and underwent liver biopsy were included in the discovery cohort. The dataset was randomly split into training and testing sets. Patients were categorized into groups with no/minimal/moderate fibrosis and advanced fibrosis. Six ML models were employed to identify the optimal model. Subsequently, the predictive capability of the best ML model was validated in an additional cohort (n = 33) and compared with conventional noninvasive fibrosis scores.</p><p><strong>Results: </strong>Three key clinical features, including prothrombin time (PT), albumin (ALB), and ultrasound spleen thickness (UTST), were analyzed by least absolute shrinkage and selection operator (LASSO) regression. In the training set, the random forest (RF) model showed the highest diagnostic performance in predicting advanced fibrosis stage (AUC=0.951). In the testing cohort and validation cohort, the RF model maintained high accuracy (AUC = 0.863 and AUC = 0.843). Additionally, the random forest model outperformed the conventional noninvasive fibrosis scores.</p><p><strong>Conclusions: </strong>ML models, particularly the RF model, can help improve the discrimination of advanced liver fibrosis in patients with AIH.</p>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":" ","pages":"101754"},"PeriodicalIF":3.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-associated macrophages contribute to cholangiocarcinoma progression and chemoresistance through activation of ID1.","authors":"Yinghao Guo, Shuangda Miao, Yun Jin, Qi Li, Yihang Wang, Xiaoxiao Zhang, Jiangtao Li","doi":"10.1016/j.aohep.2024.101773","DOIUrl":"10.1016/j.aohep.2024.101773","url":null,"abstract":"<p><strong>Introduction and objectives: </strong>Tumor-associated macrophages (TAM) can influence both cancer growth and chemoresistance, but the specific mechanisms involved in these processes in cholangiocarcinoma (CCA) are unclear.</p><p><strong>Materials and methods: </strong>We explored the distribution of TAM in CCA samples by multiplex immunofluorescence staining and tested the effects of TAM on CCA in vitro and in vivo. We then investigated the mechanisms underlying these effects using the Luminex assay, RNA sequencing, western blotting, flow cytometry, and co-immunoprecipitation.</p><p><strong>Results: </strong>The infiltration of TAM was strongly increased in the cholangiocarcinoma tumor microenvironment. Oncostain M (OSM) secreted by TAM increased the proliferation and chemotherapeutic resistance of CCA cells both in vitro and in vivo. The results of transcriptome sequencing analysis, Western blot analysis, and immunofluorescence staining confirmed that OSM can promote Yap nuclear translocation and its subsequent formation of complexes with SMADs to upregulate the expression of inhibitor of DNA binding 1 (ID1).</p><p><strong>Conclusions: </strong>TAM promotes CCA progression and chemoresistance through activating OSM-Yap-ID1.</p>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":" ","pages":"101773"},"PeriodicalIF":3.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to letter to the editor by Rodriguez S et al.","authors":"Carlos Moctezuma-Velazquez","doi":"10.1016/j.aohep.2024.101770","DOIUrl":"10.1016/j.aohep.2024.101770","url":null,"abstract":"","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":" ","pages":"101770"},"PeriodicalIF":3.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rifaximin treatment in patients with severe alcoholic hepatitis: A multicenter, randomized controlled, open-label, pilot trial.","authors":"Do Seon Song, Jin Mo Yang, Young Kul Jung, Hyung Joon Yim, Hee Yeon Kim, Chang Wook Kim, Soon Sun Kim, Jae Youn Cheong, Hae Lim Lee, Sung Won Lee, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim","doi":"10.1016/j.aohep.2024.101749","DOIUrl":"10.1016/j.aohep.2024.101749","url":null,"abstract":"<p><strong>Introduction and objectives: </strong>The short-term mortality of severe alcoholic hepatitis (SAH) is high, but there are no effective treatments to improve short-term mortality other than corticosteroids. This study investigated the effects of adding rifaximin to standard treatment in patients with SAH.</p><p><strong>Material and methods: </strong>In this randomized controlled open-label trial, patients with SAH (Maddrey's discriminant function≥32) were randomized to the rifaximin or control group. Patients were simultaneously treated with corticosteroid or pentoxifylline as standard treatment for 4 weeks. Randomization was stratified by SAH treatment.</p><p><strong>Results: </strong>A total of 49 patients were enrolled in this study (29 in the control group and 20 in the rifaximin group). The mean Model for End-stage Liver Disease (MELD) scores were 24.4 and 27.8 in the control and rifaximin groups, respectively (P = 0.083). There were no significant differences in 6-month Liver Transplantation (LT)-free survival rate between the two groups (P = 0.698). When stratified by SAH treatment, there was no significant difference in 6-month LT-free survival rate between the control and rifaximin treatment groups (P = 0.526 in the corticosteroid group and P = 0.620 in the pentoxifylline group). There were no significant differences in the occurrence of liver-related complications between the two groups (all Ps>0.05). The MELD score was the only independent factor for 6-month LT-free survival (hazard ratio 1.360, 95 % confidence interval 1.021-1.810, P = 0.035), and rifaximin was not.</p><p><strong>Conclusions: </strong>In patients with SAH, adding rifaximin to corticosteroid or pentoxifylline had no survival benefit and no preventive effect on the development of liver-related complications. The MELD score was the only significant factor for short-term mortality.</p>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":" ","pages":"101749"},"PeriodicalIF":3.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing liver fibrosis in chronic liver disease: Comparison of diffusion-weighted MR elastography and two-dimensional shear-wave elastography using histopathologic assessment as the reference standard.","authors":"Li Yang, Guofeng Zhou, Liheng Liu, Shengxiang Rao, Wentao Wang, Kaipu Jin, Caixia Fu, Mengsu Zeng, Ying Ding","doi":"10.1016/j.aohep.2024.101743","DOIUrl":"10.1016/j.aohep.2024.101743","url":null,"abstract":"<p><strong>Introduction and objectives: </strong>Liver stiffness measurement (LSM) by two-dimensional shear-wave elastography (2D SWE) is a well-established method for assessing hepatic fibrosis. Diffusion-weighted imaging (DWI) can be converted into virtual shear modulus (µ_Diff) to estimate liver elasticity. The purpose of this study was to correlate and compare the diagnostic performance of DWI-based virtual elastography and 2D SWE for staging hepatic fibrosis in patients with chronic liver disease, using histopathologic assessment as the reference standard.</p><p><strong>Patients and methods: </strong>This retrospective study included 111 patients who underwent preoperative multiple b-value DWI and 2D SWE. The µ_Diff was calculated using DWI acquisition with b-values of 200 and 1,500 /mm², and LSM was obtained by 2D SWE. Correlation between µ_Diff and LSM was assessed, as well as the correlation between these noninvasive methods and histologic fibrosis stages. The diagnostic efficacy of µ_Diff and LSM for staging liver fibrosis was compared with receiver operating characteristic (ROC) curve analysis.</p><p><strong>Results: </strong>There was a significant positive correlation between µ_Diff and LSM (rho= 0.48, P < 0.001). µ_Diff (rho= 0.54, P < 0.001) and LSM (rho= 0.76, P < 0.001) were positively correlated with liver fibrosis stages. Areas under the curves (AUCs) of µ_Diff and LSM, respectively, were 0.81 and 0.90 for significant fibrosis, 0.89 and 0.98 for advanced fibrosis, and 0.77 and 0.91 for cirrhosis. The AUCs of 2D SWE for diagnosing advanced fibrosis and cirrhosis were significantly higher than those of µ_Diff (P < 0.05 for both).</p><p><strong>Conclusions: </strong>LSM by 2D SWE yields larger AUCs compared to µ_Diff obtained from DWI-based virtual elastography for various stages of liver fibrosis. LSM is superior to µ_Diff in predicting advanced fibrosis and cirrhosis.</p>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":" ","pages":"101743"},"PeriodicalIF":3.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipocalin-2 silencing alleviates sepsis-induced liver injury through inhibition of ferroptosis.","authors":"Yuping Li, Lu Li, Yuming Zhang, Qi Yun, Ruoli Du, Hongwei Ye, Zhenghong Li, Qin Gao","doi":"10.1016/j.aohep.2024.101756","DOIUrl":"10.1016/j.aohep.2024.101756","url":null,"abstract":"<p><strong>Introduction and objectives: </strong>Liver plays a key role in sepsis, a systemic inflammatory response syndrome caused by infection. Ferroptosis is involved in sepsis-induced liver injury. We aimed to assess the changes in ferroptosis in cecal ligation and puncture (CLP)-induced septic mice, and determine the role of lipocalin-2 (LCN2) in liver ferroptosis.</p><p><strong>Materials and methods: </strong>CLP was used to induce sepsis in mice. The morphological changes in liver tissues and mitochondrial structure were observed using hematoxylin and eosin staining and transmission electron microscopy. The levels of serum alanine transaminase, aspartate aminotransferase, superoxide dismutase, and malondialdehyde were detected using the corresponding kits. The changes of reactive oxygen species level in liver tissues were detected using dihydroethidium as a fluorescence probe. LCN2, cysteine-glutamate reverse transport system, and dihydroorotate dehydrogenase protein levels in the liver were detected by western blotting. The ferroptosis inhibitor ferrostatin-1 (Fer-1), iron chelator dexrazoxane (DXZ), iron-dextran, and LCN2 knockdown studies were performed to determine role of ferroptosis and LCN2 in liver injury during sepsis.</p><p><strong>Results: </strong>Ferroptosis levels increased in the liver tissues of CLP-induced septic mice. Both Fer-1 and DXZ suppressed ferroptosis and attenuated liver injury following sepsis challenge, whereas iron-dextran increased ferroptosis and liver injury in mice with sepsis. LCN2 knockdown suppressed ferroptosis and reduced oxidative stress in the liver.</p><p><strong>Conclusions: </strong>Ferroptosis inhibition attenuates septic liver injury. LCN2 knockdown alleviates sepsis-induced liver injury by inhibiting ferroptosis and reducing oxidative stress.</p>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":" ","pages":"101756"},"PeriodicalIF":3.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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-Opinion on article by Rodriguez-Alvarez F et al.","authors":"Santiago Rodriguez, Giacomo Balbinotto Neto, Ajacio Brandão","doi":"10.1016/j.aohep.2024.101771","DOIUrl":"10.1016/j.aohep.2024.101771","url":null,"abstract":"","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":" ","pages":"101771"},"PeriodicalIF":3.7,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}