Pub Date : 2024-10-01Epub Date: 2024-07-11DOI: 10.21037/hbsn-23-677
Ali Gunduz Sarioglu, Chase J Wehrle, Ege Akgun, Arturan Ibrahimli, James F Bena, Eren Berber
Background: Ablation is an alternative treatment modality for selected patients with colorectal liver metastases (CRLMs). Although initially widely performed via radiofrequency ablation (RFA), more recently, microwave ablation (MWA) is being preferred due to its perceived superiority in creating the ablation zones. The aim of this study is to compare the long-term efficacy of these two modalities performed surgically.
Methods: Patients undergoing surgical liver ablation from 2005-2023 at a tertiary center by a single surgeon for CRLM were included in a retrospective institutional review board-approved study. Outcomes were compared using Wilcoxon, Chi-square, Kaplan-Meier, and Cox multivariate regression analyses. Continuous data are presented as median (interquartile range).
Results: There were a total of 242 patients. Laparoscopic RFA was done in 121 patients with 303 lesions and laparoscopic MWA in 121 patients with 300 lesions. There was no difference between the groups regarding operative time (161 vs. 147 minutes, respectively, P=0.4), perioperative morbidity (3% vs. 8%, respectively, P=0.2) or hospital stay (1 vs. 1 day, P=0.05). Local recurrence (LR) per lesion with at least 1 year of imaging follow-up was 29% in the RFA and 13% in the MWA group (P<0.001). Based on univariate survival analysis, tumor size, blood vessel proximity, ablation margin, and ablation modality were independent predictors of LR. To control these variables, direct matching was performed. Each cohort included 189 lesions. Kaplan-Meier analysis of these cohorts showed increased LR-free survival in the MWA group vs. the RFA group (P=0.005).
Conclusions: This large study confirms our initial observation that local tumor control rate is better after MWA vs. RFA.
背景:消融术是针对特定结直肠肝转移(CRLM)患者的一种替代治疗方式。虽然最初广泛采用的是射频消融术(RFA),但最近人们更倾向于采用微波消融术(MWA),因为微波消融术在创建消融区方面被认为更具优势。本研究旨在比较这两种手术方式的长期疗效:一项经机构审查委员会批准的回顾性研究纳入了2005-2023年期间在一家三级医疗中心由一名外科医生对CRLM进行手术肝消融的患者。采用Wilcoxon、Chi-square、Kaplan-Meier和Cox多变量回归分析对结果进行比较。连续数据以中位数(四分位数间距)表示:共有 242 名患者。121名患者的303个病灶接受了腹腔镜RFA治疗,121名患者的300个病灶接受了腹腔镜MWA治疗。两组患者的手术时间(分别为161分钟和147分钟,P=0.4)、围术期发病率(分别为3%和8%,P=0.2)或住院时间(分别为1天和1天,P=0.05)均无差异。在至少1年的影像随访中,RFA组每个病灶的局部复发率(LR)为29%,MWA组为13%(Pvs.RFA组,P=0.005):这项大型研究证实了我们最初的观察结果,即 MWA 与 RFA 相比,局部肿瘤控制率更高。
{"title":"Radiofrequency ablation versus microwave ablation for colorectal liver metastases: long-term results of a retrospective cohort surgical experience.","authors":"Ali Gunduz Sarioglu, Chase J Wehrle, Ege Akgun, Arturan Ibrahimli, James F Bena, Eren Berber","doi":"10.21037/hbsn-23-677","DOIUrl":"10.21037/hbsn-23-677","url":null,"abstract":"<p><strong>Background: </strong>Ablation is an alternative treatment modality for selected patients with colorectal liver metastases (CRLMs). Although initially widely performed via radiofrequency ablation (RFA), more recently, microwave ablation (MWA) is being preferred due to its perceived superiority in creating the ablation zones. The aim of this study is to compare the long-term efficacy of these two modalities performed surgically.</p><p><strong>Methods: </strong>Patients undergoing surgical liver ablation from 2005-2023 at a tertiary center by a single surgeon for CRLM were included in a retrospective institutional review board-approved study. Outcomes were compared using Wilcoxon, Chi-square, Kaplan-Meier, and Cox multivariate regression analyses. Continuous data are presented as median (interquartile range).</p><p><strong>Results: </strong>There were a total of 242 patients. Laparoscopic RFA was done in 121 patients with 303 lesions and laparoscopic MWA in 121 patients with 300 lesions. There was no difference between the groups regarding operative time (161 <i>vs.</i> 147 minutes, respectively, P=0.4), perioperative morbidity (3% <i>vs.</i> 8%, respectively, P=0.2) or hospital stay (1 <i>vs.</i> 1 day, P=0.05). Local recurrence (LR) per lesion with at least 1 year of imaging follow-up was 29% in the RFA and 13% in the MWA group (P<0.001). Based on univariate survival analysis, tumor size, blood vessel proximity, ablation margin, and ablation modality were independent predictors of LR. To control these variables, direct matching was performed. Each cohort included 189 lesions. Kaplan-Meier analysis of these cohorts showed increased LR-free survival in the MWA group <i>vs.</i> the RFA group (P=0.005).</p><p><strong>Conclusions: </strong>This large study confirms our initial observation that local tumor control rate is better after MWA <i>vs</i>. RFA.</p>","PeriodicalId":12878,"journal":{"name":"Hepatobiliary surgery and nutrition","volume":"13 5","pages":"759-770"},"PeriodicalIF":6.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-07-04DOI: 10.21037/hbsn-24-153
Xindi Ke, Qiaoxin Wei, Lejia Sun, Huayu Yang
{"title":"Liver microbiome: an intrahepatic resident playing a role in liver diseases.","authors":"Xindi Ke, Qiaoxin Wei, Lejia Sun, Huayu Yang","doi":"10.21037/hbsn-24-153","DOIUrl":"10.21037/hbsn-24-153","url":null,"abstract":"","PeriodicalId":12878,"journal":{"name":"Hepatobiliary surgery and nutrition","volume":"13 4","pages":"686-689"},"PeriodicalIF":6.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11336525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-07-22DOI: 10.21037/hbsn-24-217
Jie Yang, Qing Liu, Jie Li, Chao Sun
{"title":"The validity of serum ferritin levels in predicting cardiovascular events of metabolic dysfunction-associated steatotic liver disease patients may need more consideration.","authors":"Jie Yang, Qing Liu, Jie Li, Chao Sun","doi":"10.21037/hbsn-24-217","DOIUrl":"10.21037/hbsn-24-217","url":null,"abstract":"","PeriodicalId":12878,"journal":{"name":"Hepatobiliary surgery and nutrition","volume":"13 4","pages":"755-756"},"PeriodicalIF":6.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11336545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-07-23DOI: 10.21037/hbsn-24-289
Darren Weiquan Chua, Yun Zhao, Ye Xin Koh
{"title":"Critical appraisal of novel prediction models and risk calculators for post-hepatectomy liver failure and complications: practicability and generalisability in the real-world setting.","authors":"Darren Weiquan Chua, Yun Zhao, Ye Xin Koh","doi":"10.21037/hbsn-24-289","DOIUrl":"10.21037/hbsn-24-289","url":null,"abstract":"","PeriodicalId":12878,"journal":{"name":"Hepatobiliary surgery and nutrition","volume":"13 4","pages":"696-698"},"PeriodicalIF":6.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11336547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-07-23DOI: 10.21037/hbsn-24-250
Hani M Wadei, Kristopher P Croome
{"title":"Does ischemia-free machine perfusion lead to early allograft dysfunction (EAD) free liver transplantation?","authors":"Hani M Wadei, Kristopher P Croome","doi":"10.21037/hbsn-24-250","DOIUrl":"10.21037/hbsn-24-250","url":null,"abstract":"","PeriodicalId":12878,"journal":{"name":"Hepatobiliary surgery and nutrition","volume":"13 4","pages":"678-680"},"PeriodicalIF":6.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11336541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-04-18DOI: 10.21037/hbsn-23-562
Ziyan Pan, Wai-Kay Seto, Chun-Jen Liu, Yilei Mao, Saleh A Alqahtani, Mohammed Eslam
Background and objective: Hepatocellular carcinoma (HCC) poses a significant global health burden and ranks as the fifth most prevalent cancer on a global scale. Hepatitis C virus (HCV) infection remains one of the major risk factors for HCC development. HCC is a heterogeneous disease, and the development of HCC caused by HCV is intricate and involves various factors, including genetic susceptibility, viral factors, immune response due to chronic inflammation, alcohol abuse, and metabolic dysfunction associated with fatty liver disease. In this review, we provide a comprehensive and updated review of research on the genetics and epigenetic mechanisms implicated in developing HCC associated with HCV infection. We also discuss the potential translational implications, including novel biomarkers and drugs for treatment.
Methods: A comprehensive literature search was conducted in June 2023 in PubMed and Embase databases.
Key content and findings: Recent findings indicate that a variety of genetic and epigenetic processes are involved in the pathogenesis and continue to exist even after the complete elimination of HCV. The deregulation of the epigenome has been identified as a significant factor in the deletrious effects of liver disease, especially during the initial stages when genetic alterations are uncommon. The enduring "epigenetic memory" of gene expression is believed to be regulated by epigenetic mechanisms, indicating that alterations caused by HCV infection continue to exist and are linked to the risk of development of liver cancer even after successful treatment. Systems biology analytical methods will be required to delineate the magnitude and significance of both genetic and epigenomic alterations in tumor evolution.
Conclusions: By facilitating a more profound understanding of these aspects, this will ultimately foster the advancement of novel therapies and ultimately improve outcomes for patients.
{"title":"A literature review of genetics and epigenetics of HCV-related hepatocellular carcinoma: translational impact.","authors":"Ziyan Pan, Wai-Kay Seto, Chun-Jen Liu, Yilei Mao, Saleh A Alqahtani, Mohammed Eslam","doi":"10.21037/hbsn-23-562","DOIUrl":"10.21037/hbsn-23-562","url":null,"abstract":"<p><strong>Background and objective: </strong>Hepatocellular carcinoma (HCC) poses a significant global health burden and ranks as the fifth most prevalent cancer on a global scale. Hepatitis C virus (HCV) infection remains one of the major risk factors for HCC development. HCC is a heterogeneous disease, and the development of HCC caused by HCV is intricate and involves various factors, including genetic susceptibility, viral factors, immune response due to chronic inflammation, alcohol abuse, and metabolic dysfunction associated with fatty liver disease. In this review, we provide a comprehensive and updated review of research on the genetics and epigenetic mechanisms implicated in developing HCC associated with HCV infection. We also discuss the potential translational implications, including novel biomarkers and drugs for treatment.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted in June 2023 in PubMed and Embase databases.</p><p><strong>Key content and findings: </strong>Recent findings indicate that a variety of genetic and epigenetic processes are involved in the pathogenesis and continue to exist even after the complete elimination of HCV. The deregulation of the epigenome has been identified as a significant factor in the deletrious effects of liver disease, especially during the initial stages when genetic alterations are uncommon. The enduring \"epigenetic memory\" of gene expression is believed to be regulated by epigenetic mechanisms, indicating that alterations caused by HCV infection continue to exist and are linked to the risk of development of liver cancer even after successful treatment. Systems biology analytical methods will be required to delineate the magnitude and significance of both genetic and epigenomic alterations in tumor evolution.</p><p><strong>Conclusions: </strong>By facilitating a more profound understanding of these aspects, this will ultimately foster the advancement of novel therapies and ultimately improve outcomes for patients.</p>","PeriodicalId":12878,"journal":{"name":"Hepatobiliary surgery and nutrition","volume":"13 4","pages":"650-661"},"PeriodicalIF":6.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11336528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-07-05DOI: 10.21037/hbsn-23-616
Chee-Chien Yong, Hsu-Ting Yen, Yu-Fan Cheng, Leona Bettina Dungca, Raymond Joseph De Vera, Itsuko Chih-Yi Chen, Chao-Long Chen
The Meso-Rex bypass (MRB) is recognized as an effective treatment for portal hypertension secondary to extrahepatic portal vein occlusion (EHPVO) both in the pediatric and adult population, within or outside the context of liver transplantation. It is the preferred surgical treatment in most centers because not only does it addresses the portal hypertension, but also restores physiologic portal hepatopetal flow. However, the Rex recess, the landmark for this technique, may not be safely accessible in some patients. We present a 22-year-old male who underwent living donor liver transplant (LDLT) for neonatal hepatitis. He presented with variceal bleeding due to EHPVO at 13 years after transplant. Various endoscopic, radiologic, and surgical interventions were employed to address the recurrent gastrointestinal bleeding, but results have been unsatisfactory. We performed a meso-intrahepatic portal vein bypass (MIPVB), an innovative alternative to the MRB, for this patient with extensive post-operative adhesions, perihilar collaterals, and cavernous transformation. MIPVB creation in patients where the Rex recess is inaccessible is technically challenging. But with a multidisciplinary team approach, meticulous preoperative planning, and close follow-up, the authors have demonstrated that it is a safe and feasible option for patients with late-onset EHPVO after liver transplantation.
{"title":"Beyond the Rex: an innovative meso-intrahepatic portal vein bypass for late-onset extrahepatic portal vein occlusion after living donor liver transplantation.","authors":"Chee-Chien Yong, Hsu-Ting Yen, Yu-Fan Cheng, Leona Bettina Dungca, Raymond Joseph De Vera, Itsuko Chih-Yi Chen, Chao-Long Chen","doi":"10.21037/hbsn-23-616","DOIUrl":"10.21037/hbsn-23-616","url":null,"abstract":"<p><p>The Meso-Rex bypass (MRB) is recognized as an effective treatment for portal hypertension secondary to extrahepatic portal vein occlusion (EHPVO) both in the pediatric and adult population, within or outside the context of liver transplantation. It is the preferred surgical treatment in most centers because not only does it addresses the portal hypertension, but also restores physiologic portal hepatopetal flow. However, the Rex recess, the landmark for this technique, may not be safely accessible in some patients. We present a 22-year-old male who underwent living donor liver transplant (LDLT) for neonatal hepatitis. He presented with variceal bleeding due to EHPVO at 13 years after transplant. Various endoscopic, radiologic, and surgical interventions were employed to address the recurrent gastrointestinal bleeding, but results have been unsatisfactory. We performed a meso-intrahepatic portal vein bypass (MIPVB), an innovative alternative to the MRB, for this patient with extensive post-operative adhesions, perihilar collaterals, and cavernous transformation. MIPVB creation in patients where the Rex recess is inaccessible is technically challenging. But with a multidisciplinary team approach, meticulous preoperative planning, and close follow-up, the authors have demonstrated that it is a safe and feasible option for patients with late-onset EHPVO after liver transplantation.</p>","PeriodicalId":12878,"journal":{"name":"Hepatobiliary surgery and nutrition","volume":"13 4","pages":"662-668"},"PeriodicalIF":6.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11336526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-07-23DOI: 10.21037/hbsn-24-292
Massimo Primignani, Giulia Tosetti, Andrea Artoni
{"title":"High risk of thrombosis recurrence in people with idiopathic or only locally caused non-cirrhotic splanchnic vein thrombosis: it is time for guidelines' revision.","authors":"Massimo Primignani, Giulia Tosetti, Andrea Artoni","doi":"10.21037/hbsn-24-292","DOIUrl":"10.21037/hbsn-24-292","url":null,"abstract":"","PeriodicalId":12878,"journal":{"name":"Hepatobiliary surgery and nutrition","volume":"13 4","pages":"699-702"},"PeriodicalIF":6.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11336550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-07-18DOI: 10.21037/hbsn-24-301
Chase J Wehrle, Charles Miller, Koji Hashimoto, Andrea Schlegel
{"title":"Standardization is needed in reporting risk and outcomes of machine perfusion in liver transplantation.","authors":"Chase J Wehrle, Charles Miller, Koji Hashimoto, Andrea Schlegel","doi":"10.21037/hbsn-24-301","DOIUrl":"10.21037/hbsn-24-301","url":null,"abstract":"","PeriodicalId":12878,"journal":{"name":"Hepatobiliary surgery and nutrition","volume":"13 4","pages":"709-714"},"PeriodicalIF":6.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11336534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-01-12DOI: 10.21037/hbsn-23-400
Yiran Li, Ziyu Xun, Junyu Long, Huishan Sun, Xu Yang, Yanyu Wang, Yunchao Wang, Jingnan Xue, Nan Zhang, Junwei Zhang, Jin Bian, Jie Shi, Xiaobo Yang, Hanping Wang, Haitao Zhao
Background: Hepatocholangiocarcinoma (H-ChC) has the clinicopathological features of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) and is a more aggressive subtype of primary hepatic carcinoma than HCC or iCCA.
Methods: We sequenced 91,112 single-cell transcriptomes from 16 human samples to elucidate the molecular mechanisms underlying the coexistence of HCC and iCCA components in H-ChC.
Results: We observed two molecular subtypes of H-ChC at the whole-transcriptome level (CHP and CIP), where a metabolically active tumour cell subpopulation enriched in CHP was characterized by a cellular pre-differentiation property. To define the heterogeneity of tumours and their associated microenvironments, we observe greater tumour diversity in H-ChC than HCC and iCCA. H-ChC exhibits weaker immune cell infiltration and greater CD8+ exhausted T cell (Tex) dysfunction than HCC and iCCA. Then we defined two broad cell states of 6,852 CD8+ Tex cells: GZMK+ CD8+ Tex cells and terminal CD8+ Tex cells. GZMK+ CD8+ Tex cells exhibited higher infiltration of after treatment in H-ChC, the effector scores and expression of the immune checkpoints of them greatly increased after immunotherapy, which indicated that H-ChC might be more sensitive than HCC or iCCA to immunotherapy.
Conclusions: In this paper, H-ChC was explored, hoping to contribute to the study of mixed tumours in other cancers.
{"title":"Immunosuppression and phenotypic plasticity in an atlas of human hepatocholangiocarcinoma.","authors":"Yiran Li, Ziyu Xun, Junyu Long, Huishan Sun, Xu Yang, Yanyu Wang, Yunchao Wang, Jingnan Xue, Nan Zhang, Junwei Zhang, Jin Bian, Jie Shi, Xiaobo Yang, Hanping Wang, Haitao Zhao","doi":"10.21037/hbsn-23-400","DOIUrl":"10.21037/hbsn-23-400","url":null,"abstract":"<p><strong>Background: </strong>Hepatocholangiocarcinoma (H-ChC) has the clinicopathological features of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) and is a more aggressive subtype of primary hepatic carcinoma than HCC or iCCA.</p><p><strong>Methods: </strong>We sequenced 91,112 single-cell transcriptomes from 16 human samples to elucidate the molecular mechanisms underlying the coexistence of HCC and iCCA components in H-ChC.</p><p><strong>Results: </strong>We observed two molecular subtypes of H-ChC at the whole-transcriptome level (CHP and CIP), where a metabolically active tumour cell subpopulation enriched in CHP was characterized by a cellular pre-differentiation property. To define the heterogeneity of tumours and their associated microenvironments, we observe greater tumour diversity in H-ChC than HCC and iCCA. H-ChC exhibits weaker immune cell infiltration and greater CD8<sup>+</sup> exhausted T cell (Tex) dysfunction than HCC and iCCA. Then we defined two broad cell states of 6,852 CD8<sup>+</sup> Tex cells: GZMK<sup>+</sup> CD8<sup>+</sup> Tex cells and terminal CD8<sup>+</sup> Tex cells. GZMK<sup>+</sup> CD8<sup>+</sup> Tex cells exhibited higher infiltration of after treatment in H-ChC, the effector scores and expression of the immune checkpoints of them greatly increased after immunotherapy, which indicated that H-ChC might be more sensitive than HCC or iCCA to immunotherapy.</p><p><strong>Conclusions: </strong>In this paper, H-ChC was explored, hoping to contribute to the study of mixed tumours in other cancers.</p>","PeriodicalId":12878,"journal":{"name":"Hepatobiliary surgery and nutrition","volume":"13 4","pages":"586-603"},"PeriodicalIF":6.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11336540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}