Clinical and Molecular Hepatology最新文献

{"title":"A leap in the dark: Bariatric surgery for treatment of metabolic dysfunction-associated steatotic liver disease related cirrhosis.","authors":"Jing Zeng, Jian-Gao Fan","doi":"10.3350/cmh.2024.1099","DOIUrl":"https://doi.org/10.3350/cmh.2024.1099","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846078","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":"Global Inequality in the Burden of Hepatitis B From 1990 to 2021: Findings From the Global Burden of Disease Study 2021.","authors":"Chunlong Liu, Jiangtao Yu","doi":"10.3350/cmh.2024.1085","DOIUrl":"https://doi.org/10.3350/cmh.2024.1085","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846086","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":"Comment on: Evolutionary changes in metabolic dysfunction-associated steatotic liver disease and risk of hepatocellular carcinoma.","authors":"Hai Xu, Yong Zhou, Huikun Wu","doi":"10.3350/cmh.2024.1087","DOIUrl":"https://doi.org/10.3350/cmh.2024.1087","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846083","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":"Plasma lipidomics and fungal peptide-based community analysis identifies distinct signatures of early mortality in acute liver failure.","authors":"Neha Sharma, Sushmita Pandey, Gaurav Tripathi, Manisha Yadav, Nupur Sharma, Babu Mathew, Abhishak Gupta, Vasundhra Bindal, Sadam H Bhat, Yash Magar, Rimsha Saif, Sanju Yadav, Amritpal Kaur, Rakhi Maiwall, Shvetank Sharma, Shiv Kumar Sarin, Jaswinder Singh Maras","doi":"10.3350/cmh.2024.0554","DOIUrl":"https://doi.org/10.3350/cmh.2024.0554","url":null,"abstract":"<p><strong>Background and aims: </strong>Acute liver failure (ALF) has high mortality predominantly due to compromised immune system and increase vulnerability to bacterial and fungal infections.</p><p><strong>Method: </strong>Plasma lipidome and fungal peptide-based-community (mycobiome) analysis were performed in Discovery cohort (40-ALF, 5-healthy) and validated in a validation cohort of 230-ALF using High-resolution-mass-spectrometry, artificial-neural-network (ANN) and machine-learning (ML).</p><p><strong>Results: </strong>Untargeted lipidomics identified 2,013 lipids across 8 lipid-groups. 5 lipid-species (Phosphatidylcholine, PC(15:0/17:0), PC(20:1/14:1), PC(26:4/10:0), PC(32:0) and TG(4:0/10:0/23:6)) significantly differentiated ALF-NS (FC>10, p<0.05, FDR<0.01). Mycobiome (alpha/beta diversity) was significantly higher and showed 4 phyla and >20 species significantly dysregulated in ALF-NS linked with lipid-metabolism, fatty-acid-elongation in ER, and others (p<0.05). Lipid and mycobiome diversity in ALF-NS were strongly correlated(r2>0.7, p<0.05). Multi-modular correlation network showed striking associations between lipid, Fungal-peptides modules, and Clinical parameters specific to ALF-NS (p<0.05). Cryptococcus amylolentus CBS6039 and Penicillium oxalicum1142 directly correlated with Phosphatidylcholine, Triglycerides, and severity in ALF-NS(r2>0.85, p<0.05). POD-fungus and POD-lipids showed direct association with infection, necrosis, and hepatic encephalopathy (Beta>1.2, p<0.05). POD-lipid (AUC=0.969) and HR=1.99(1.02-2.04) superseded POD-fungus and severity indices for early-mortality prediction. Finally, significant increase in PC(15:0/17:0) level showed highest normalized importance and predicted early-mortality with >95% accuracy/sensitivity/specificity using ANN and ML. Interestingly, fungal surveillance protein Clec7a was significantly downregulated (>2-fold), leading to a notable rise in fungal infection-mediated choline/phosphatidylcholine and associated enzymes (FC>1.5; Kennedy cycle). This contributed to phosphatidic acid-mediated hyper-inflammation in ALF-non-survivors.</p><p><strong>Conclusion: </strong>In ALF plasma lipidome and mycobiome are dysregulated. Increase circulating phosphatidylcholine could stratify ALF predisposed to early-mortality or require emergency liver transplantation.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827195","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":"Gut microbiota-mediated gut-liver axis: a breakthrough point for understanding and treating liver cancer.","authors":"Chenyang Li, Chujun Cai, Chendong Wang, Xiaoping Chen, Bixiang Zhang, Zhao Huang","doi":"10.3350/cmh.2024.0857","DOIUrl":"https://doi.org/10.3350/cmh.2024.0857","url":null,"abstract":"<p><p>The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver though a unique gut-liver axis. Disruptions in the gut microbial communities, arising from environmental and genetic factors, can lead to altered microbial metabolism, impaired intestinal barrier and translocation of microbial components to the liver. These alterations collaboratively contribute to the pathogenesis of liver disease, and their continuous impact throughout the disease course plays a critical role in hepatocarcinogenesis. Persistent inflammatory responses, metabolic rearrangements and suppressed immunosurveillance induced by microbial products underlie the pro-carcinogenic mechanisms of gut microbiota. Meanwhile, intrahepatic microbiota derived from the gut also emerges as a novel player in the development and progression of liver cancer. In this review, we first discuss the causes of gut dysbiosis in liver disease, and then specify the pivotal role of gut microbiota in the malignant progression from chronic liver diseases to hepatobiliary cancers. We also delve into the cellular and molecular interactions between microbes and liver cancer microenvironment, aiming to decipher the underlying mechanism for the malignant transition processes. At last, we summarize the current progress in the clinical implications of gut microbiota for liver cancer, shedding light on microbiota-based strategies for liver cancer prevention, diagnosis and therapy.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806271","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":"Integrated Molecular Characterization of Sarcomatoid Hepatocellular Carcinoma.","authors":"Rong-Qi Sun, Yu-Hang Ye, Ye Xu, Bo Wang, Si-Yuan Pan, Ning Li, Long Chen, Jing-Yue Pan, Zhi-Qiang Hu, Jia Fan, Zheng-Jun Zhou, Jian Zhou, Cheng-Li Song, Shao-Lai Zhou","doi":"10.3350/cmh.2024.0686","DOIUrl":"https://doi.org/10.3350/cmh.2024.0686","url":null,"abstract":"<p><strong>Background: </strong>Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated.</p><p><strong>Methods: </strong>In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs.</p><p><strong>Results: </strong>Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial-mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1-5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment.</p><p><strong>Conclusions: </strong>We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806274","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":"Prediction and Management of Small-for-Size Syndrome in Living Donor Liver Transplantation.","authors":"Jia-Hao Law, Alfred Wei-Chieh Kow","doi":"10.3350/cmh.2024.0870","DOIUrl":"https://doi.org/10.3350/cmh.2024.0870","url":null,"abstract":"<p><p>Small-for-Size Syndrome (SFSS) remains a critical challenge in living donor liver transplantation (LDLT), characterized by graft insufficiency due to inadequate liver volume, leading to significant postoperative morbidity and mortality. As the global adoption of LDLT increases, the ability to predict and manage SFSS has become paramount in optimizing recipient outcomes. This review provides a comprehensive examination of the pathophysiology, risk factors, and strategies for managing SFSS across the pre-, intra-, and postoperative phases. The pathophysiology of SFSS has evolved from being solely volume-based to incorporating portal hemodynamics, now recognized as Small-for-Flow Syndrome. Key risk factors include donor-related parameters like age and graft volume, recipient-related factors such as MELD score and portal hypertension, and intraoperative factors related to venous outflow and portal inflow modulation. Current strategies to mitigate SFSS include careful graft selection based on graft-to-recipient weight ratio and liver volumetry, surgical techniques to optimize portal hemodynamics, and novel interventions such as splenic artery ligation and hemiportocaval shunts. Pharmacological agents like somatostatin and terlipressin have also shown promise in modulating portal pressure. Advances in 3D imaging and artificial intelligence-based volumetry further aid in preoperative planning. This review emphasizes the importance of a multifaceted approach to prevent and manage SFSS, advocating for standardized definitions and grading systems. Through an integrated approach to surgical techniques, hemodynamic monitoring, and perioperative management, significant strides can be made in improving the outcomes of LDLT recipients. Further research is necessary to refine these strategies and expand the application of LDLT, especially in challenging cases involving small-for-size grafts.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806276","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 Fibrosis-4 index for advanced liver fibrosis in NAFLD with T2DM: Half a loaf is better than no bread.","authors":"Zeyu Wang, Dong Wan, Meidong Xu, Yong Jiang","doi":"10.3350/cmh.2024.0993","DOIUrl":"https://doi.org/10.3350/cmh.2024.0993","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806281","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":"GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers.","authors":"Yi-Tong Li, Wei-Qing Shao, Zhen-Mei Chen, Xiao-Chen Ma, Chen-He Yi, Bao-Rui Tao, Bo Zhang, Yue Ma, Guo Zhang, Rui Zhang, Yan Geng, Jing Lin, Jin-Hong Chen","doi":"10.3350/cmh.2024.0657","DOIUrl":"https://doi.org/10.3350/cmh.2024.0657","url":null,"abstract":"<p><strong>Background/aims: </strong>Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation.</p><p><strong>Methods: </strong>The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation.</p><p><strong>Results: </strong>MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1 knockout decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP-binding cassette subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs.</p><p><strong>Conclusion: </strong>In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806268","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":"Reconsidering Treatment Indications for Chronic Hepatitis B: Insights from the TORCH-B Roll-Over Study.","authors":"Chih-Wen Wang, Ming-Lung Yu","doi":"10.3350/cmh.2024.1078","DOIUrl":"https://doi.org/10.3350/cmh.2024.1078","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766664","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}