Hepatology最新文献_第4页

Back to phosphodiesterase inhibitors for liver disease: Are we ready for clinical trials? 回到治疗肝病的磷酸二酯酶抑制剂：我们准备好进行临床试验了吗？

IF 12.9 1区医学

Hepatology Pub Date : 2025-04-01 Epub Date: 2024-08-08 DOI: 10.1097/HEP.0000000000001053

Leila Gobejishvili, Craig J McClain

引用次数: 0

Comprehensive profiling of lipid metabolic reprogramming expands precision medicine for HCC. 脂质代谢重编程的全面剖析拓展了肝细胞癌的精准医疗。

IF 12.9 1区医学

Hepatology Pub Date : 2025-04-01 Epub Date: 2024-06-19 DOI: 10.1097/HEP.0000000000000962

Qingbin Liu, Xiangyu Zhang, Jingjing Qi, Xinchen Tian, Eva Dovjak, Jiaqi Zhang, Honghuan Du, Ni Zhang, Jing Zhao, Yiming Zhang, Lijuan Wang, Yangang Wei, Chenqiao Liu, Ruikun Qian, Longquan Xiang, Weiyang Li, Peng Xiu, Changlin Ma, Yong Yu, Shulong Jiang

{"title":"Comprehensive profiling of lipid metabolic reprogramming expands precision medicine for HCC.","authors":"Qingbin Liu, Xiangyu Zhang, Jingjing Qi, Xinchen Tian, Eva Dovjak, Jiaqi Zhang, Honghuan Du, Ni Zhang, Jing Zhao, Yiming Zhang, Lijuan Wang, Yangang Wei, Chenqiao Liu, Ruikun Qian, Longquan Xiang, Weiyang Li, Peng Xiu, Changlin Ma, Yong Yu, Shulong Jiang","doi":"10.1097/HEP.0000000000000962","DOIUrl":"10.1097/HEP.0000000000000962","url":null,"abstract":"Background and aims: Liver HCC is the second leading cause of cancer-related deaths worldwide. The heterogeneity of this malignancy is driven by a wide range of genetic alterations, leading to a lack of effective therapeutic options. In this study, we conducted a systematic multi-omics characterization of HCC to uncover its metabolic reprogramming signature.Approach and results: Through a comprehensive analysis incorporating transcriptomic, metabolomic, and lipidomic investigations, we identified significant changes in metabolic pathways related to glucose flux, lipid oxidation and degradation, and de novo lipogenesis in HCC. The lipidomic analysis revealed abnormal alterations in glycerol-lipids, phosphatidylcholine, and sphingolipid derivatives. Machine-learning techniques identified a panel of genes associated with lipid metabolism as common biomarkers for HCC across different etiologies. Our findings suggest that targeting phosphatidylcholine with saturated fatty acids and long-chain sphingolipid biosynthesis pathways, particularly by inhibiting lysophosphatidylcholine acyltransferase 1 ( LPCAT1 ) and ceramide synthase 5 ( CERS5 ) as potential therapeutic strategies for HCC in vivo and in vitro. Notably, our data revealed an oncogenic role of CERS5 in promoting tumor progression through lipophagy.Conclusions: In conclusion, our study elucidates the metabolic reprogramming nature of lipid metabolism in HCC, identifies prognostic markers and therapeutic targets, and highlights potential metabolism-related targets for therapeutic intervention in HCC.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"1164-1180"},"PeriodicalIF":12.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11902616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141425893","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}

引用次数: 0

Integrative single-cell and spatial transcriptomic analyses identify a pathogenic cholangiocyte niche and TNFRSF12A as therapeutic target for biliary atresia. 单细胞和空间转录组学综合分析确定了致病性胆管细胞生态位和作为胆道闭锁治疗靶点的 TNFRSF12A。

IF 12.9 1区医学

Hepatology Pub Date : 2025-04-01 Epub Date: 2024-08-23 DOI: 10.1097/HEP.0000000000001064

Man-Huan Xiao, Dong Ma, Sihan Wu, Zaoli Huang, Peishi Liang, Huadong Chen, Zhihai Zhong, Wei Li, Fen Wang, Yanlai Tang, Juncheng Liu, Hong Jiang, Xuyang Feng, Zhenhua Luo

{"title":"Integrative single-cell and spatial transcriptomic analyses identify a pathogenic cholangiocyte niche and TNFRSF12A as therapeutic target for biliary atresia.","authors":"Man-Huan Xiao, Dong Ma, Sihan Wu, Zaoli Huang, Peishi Liang, Huadong Chen, Zhihai Zhong, Wei Li, Fen Wang, Yanlai Tang, Juncheng Liu, Hong Jiang, Xuyang Feng, Zhenhua Luo","doi":"10.1097/HEP.0000000000001064","DOIUrl":"10.1097/HEP.0000000000001064","url":null,"abstract":"Background and aims: Biliary atresia (BA) is a devastating fibroinflammatory biliary disease that is the leading indication for pediatric liver transplants worldwide. Although cholangiocytes are the primary target cells, the pathogenic mechanisms involving cholangiocytes remain elusive. Here, we aimed to characterize the pathogenic role of cholangiocytes in BA.Approach and results: Integration of single-cell RNA sequencing of 12 liver tissues (from 9 BA and 3 controls) and the spatial transcriptome of another four liver sections (from 2 BA and 2 controls) provided a comprehensive spatial liver cell atlas of BA. In particular, we identified a cholangiocyte-enriched spatial niche with infiltration of activated HSCs, activated portal fibroblasts, macrovascular endothelial cells, and TREM2 + macrophages that were elevated in the portal triad of BA. This niche was positively correlated with bile duct profiles, liver fibrosis, and poor survival in 2 independent cohorts of patients with BA. Using integrative bioinformatics analyses to mine the cell-cell communication and regulatory network in BA cholangiocytes, we uncovered the fibroinflammatory phenotype of cholangiocytes with TNFSF12-TNFRSF12A as a significant signal. Genetic ablation or blockade of TNFRSF12A suppresses liver injury, inflammation, and bile duct profiles in a mouse model of disease. Using human biliary organoids, we revealed that BA organoids expressed higher levels of CCL2 in response to TNFSF12 stimulation and promoted monocyte chemotaxis via the CCL2-CCR2 axis.Conclusions: Pathogenic cholangiocytes-enriched niche identifies TNFRSF12A as a potential therapeutic target for BA.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"1146-1163"},"PeriodicalIF":12.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142043805","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}

引用次数: 0

Erratum: Theranostical nanosystem-mediated identification of an oncogene and highly effective therapy in hepatocellular carcinoma

IF 13.5 1区医学

Hepatology Pub Date : 2025-03-28 DOI: 10.1097/hep.0000000000001240

Yu Guo, Jing Wang, Lu Zhang, Shunli Shen, Ruomi Guo, Yang Yang, Wenjie Chen, Yiru Wang, Guihua Chen, Xintao Shuai

引用次数: 0

Comparative effectiveness of immunotherapy versus lenvatinib in advanced hepatocellular carcinoma: A real-world analysis using target trial emulation. 晚期肝细胞癌中免疫疗法与来伐替尼的疗效比较：利用靶向试验模拟进行的真实世界分析。

IF 12.9 1区医学

Hepatology Pub Date : 2025-03-28 DOI: 10.1097/HEP.0000000000001328

Joseph C Ahn, Wee Han Ng, Yee Hui Yeo, Hyun-Seok Kim, Yun Wang, Hirsh Trivedi, Walid S Ayoub, Alexander Kuo, Nicole Rich, Neehar D Parikh, Ghassan K Abou-Alfa, Kevin Sheng-Kai Ma, Amit G Singal, Ju Dong Yang

{"title":"Comparative effectiveness of immunotherapy versus lenvatinib in advanced hepatocellular carcinoma: A real-world analysis using target trial emulation.","authors":"Joseph C Ahn, Wee Han Ng, Yee Hui Yeo, Hyun-Seok Kim, Yun Wang, Hirsh Trivedi, Walid S Ayoub, Alexander Kuo, Nicole Rich, Neehar D Parikh, Ghassan K Abou-Alfa, Kevin Sheng-Kai Ma, Amit G Singal, Ju Dong Yang","doi":"10.1097/HEP.0000000000001328","DOIUrl":"10.1097/HEP.0000000000001328","url":null,"abstract":"Background aims: Immunotherapy has emerged as an effective treatment for advanced hepatocellular carcinoma (HCC). We aimed to investigate the real-world effectiveness of immunotherapy compared to lenvatinib in HCC.Approach result: From the TriNetX database, we used a target trial emulation framework and identified HCC patients who received first-line treatment with immunotherapy (atezolizumab/bevacizumab or tremelimumab/durvalumab) or lenvatinib between or between August 2018 and December 2023. Overall survival (OS) was compared using Kaplan-Meier analysis and Cox proportional hazards regression. After propensity score matching, 1203 patients were included in each group. Immunotherapy was associated with improved OS vs. lenvatinib (median survival: 545 vs. 425 days; hazard ratio [HR]: 0.86, 95% confidence interval [CI]: 0.76-0.97). Regarding treatment type, atezolizumab plus bevacizumab showed improved survival compared to lenvatinib (n=1070 in each group; HR: 0.87, 95% CI: 0.77-0.99), while the point estimate favored durvalumab plus tremelimumab vs. lenvatinib (HR: 0.81, 95% CI: 0.59-1.12), though this difference was not statistically significant, likely due to small sample size. Regarding etiology, immunotherapy had improved OS compared to lenvatinib in viral hepatitis (n=510 in each group; HR: 0.74, 95% CI: 0.61-0.89) and alcoholic liver disease (n=190 in each group; HR: 0.65, 95% CI: 0.49-0.87), but not in metabolic dysfunction-associated steatotic liver diseases (n=156 in each group; HR: 0.96, 95% CI: 0.70-1.31).Conclusions: In this real-world analysis, immunotherapy was associated with improved OS compared to lenvatinib in advanced HCC, with consistent benefit across most subgroups. These findings support the use of immunotherapy as a first-line treatment for advanced HCC.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":12.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735573","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}

引用次数: 0

Erratum: Lipocalin-2 activates hepatic stellate cells and promotes nonalcoholic steatohepatitis in high-fat diet-fed Ob/Ob mice.

IF 12.9 1区医学

Hepatology Pub Date : 2025-03-27 DOI: 10.1097/HEP.0000000000001287

Kyung Eun Kim, Jaewoong Lee, Hyun Joo Shin, Eun Ae Jeong, Hye Min Jang, Yu Jeong Ahn, Hyeong Seok An, Jong Youl Lee, Meong Cheol Shin, Soo Kyoung Kim, Won Gi Yoo, Won Ho Kim, Gu Seob Roh

引用次数: 0

Reply: Targeted enteral feeding for malnutrition in Liver Transplant candidates.

IF 12.9 1区医学

Hepatology Pub Date : 2025-03-25 DOI: 10.1097/HEP.0000000000001319

Brooke Chapman, Darren Wong, Marie Sinclair, Penelope Hey, Ryma Terbah, Paul Gow, Avik Majumdar, Adam Testro

引用次数: 0

Letter to the Editor: Primary sclerosing cholangitis and autoimmune hepatitis - distinct or common autoimmune penetrance?

IF 12.9 1区医学

Hepatology Pub Date : 2025-03-25 DOI: 10.1097/HEP.0000000000001325

Lisbet Grønbæk, Hendrik Vilstrup, Peter Jepsen

引用次数: 0

Deciphering the spatial tumor microenvironment in intrahepatic cholangiocarcinoma