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Key role of interferon regulatory factor 1(IRF-1)in regulating liver disease:progress and outlook

Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第6期25卷 451-470页

作者： Tao CHEN Shipeng LI Dewen DENG Weiye ZHANG Jianjun ZHANG Zhongyang SHEN First Central Clinical School Tianjin Medical UniversityTianjin 300192China Department of organ transplant Tianjin First Central HospitalTianjin 300192China Research institute of transplant Medicine Nankai UniversityTianjin 300192China Department of Hepatobiliary Surgery Henan Provincial People’s HospitalZhengzhou 450000China Key Laboratory of organ transplant Tianjin First Central HospitalTianjin 300192China

Interferon regulatory factor 1(IRF-1)is a member of the IRF *** is the first transcription factor to be identified that could bind to the interferon-stimulated response element(ISRE)on the target gene and displays crucial roles in the interferoninduced signals and ***-1,as an important medium,has all of the advantages of full cell cycle regulation,cell death signaling transduction,and reinforcing immune surveillance,which are well *** studies indicate that IRF-1 is of vital importance to the occurrence and evolution of multifarious liver diseases,including but not limited to inhibiting the replication of the hepatitis virus(A/B/C/E),alleviating the progression of liver fibrosis,and aggravating hepatic ischemiareperfusion injury(HIRI).The tumor suppression of IRF-1 is related to the clinical characteristics of liver cancer patients,which makes it a potential indicator for predicting the prognosis and recurrence of liver cancer;additionally,the latest studies have revealed other effects of IRF-1 such as protection against alcoholic/non-alcoholic fatty liver disease(AFLD/NAFLD),cholangiocarcinoma suppression,and uncommon traits in other liver diseases that had previously received little ***,several compounds and drugs have featured a protective function in specific liver disease models in which there is significant involvement of the IRF-1 *** this paper,we hope to propose a prospective research basis upon which to help decipher translational medicine applications of IRF-1 in liver disease treatment.

关键词： Interferon regulatory factor(IRF-1) Hepatitis virus Liver fibrosis Hepatic ischemia-reperfusion injury(HIRI) Liver cancer

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Bio-analysis of Saliva Using Paper Devices and Colorimetric Assays

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Journal of Analysis and Testing 2024年第1期8卷 114-132页

作者： Adhan Narasimhan Harshil Jain Kowshika Muniandy Raja Chinnappan Naresh Kumar Mani Microfluidics Sensors and Diagnostics(μSenD)LaboratoryCentre for MicrofluidicsBiomarkersPhotoceutics&Sensors(μBioPS)Department of BiotechnologyManipal Institute of TechnologyManipal Academy of Higher EducationManipalKarnataka 576104India College of Medicine Alfaisal UniversityRiyadh 11533SaudiArabia Tissue/organ Bioengineering&BioMEMS Lab Organ Transplant Centre of ExcellenceTransplant Research&Innovation DepartmentKing Faisal Specialist Hospital and Research CentreRiyadhSaudi Arabia

In light of the evolving nature of various diseases,time becomes a crucial factor in diagnosis and identifying the underlying causes.A point-of-care device provides a rapid diagnosis of a disease without using complex and advanced instruments,which are costly and difficult to transport.A paper-based device is a relatively frugal solution wherein the paper is used as a substratum in which the reactions are carried *** methods are non-invasive,and the sample collection is relatively *** is one such body fluid in which various biomarkers are present for numerous *** of saliva has attracted more attention recently due to its non-invasiveness and *** the discovery of clinical biomarkers from salivary analysis has the potential to revolutionize the healthcare sector by providing crucial information to monitor the health status of individuals and disease progression which enables personalized *** review provides the limitation of the traditional methods in clinical applications and highlights the significance of saliva as a non-invasive biological fluid that is a source of multiple biomarkers associated with various *** also provides insights into the different paper-based colorimetric microfluidic devices developed against salivary biomarkers in the past *** major challenges in the point-of-care application and the future prospects have been discussed as ***,we also emphasize the importance of this approach in dental disease diagnosis which is least explored and holds potential applications.

关键词： Paper-based assay Salivary analysis Non-invasive Point-of-care Body fluids Biomarkers Qualitative detection

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FGF21-mediated autophagy:Remodeling the homeostasis in response to stress in liver diseases

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Genes & Diseases 2024年第3期11卷 264-274页

作者： Wei Shen Modan Yang Hao Chen Chiy He Huigang Li Xinyu Yang Jianyong Zhuo Zuyuan Lin Zhihang Hu Di Lu Xiao Xu Zhejiang University School of Medicine HangzhouZhejiang 310058China Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Department of Hepatobiliary and Pancreatic SurgeryAffiliated Hangzhou First People's HospitalZhejiang University School of MedicineHangzhouZhejiang 310006China The institute for organ Repair and Regenerative Medicine of Hangzhou HangzhouZhejiang 310006China institute of organ transplantation Zhejiang UniversityHangzhouZhejiang 310003China National Center for Healthcare Quality Management in Liver transplant HangzhouZhejiang 310003China

Liver diseases are worldwide problems closely associated with various stresses,such as endoplasmic reticulum *** exact interplay between stress and liver diseases remains *** plays an essential role in maintaining homeostasis,and recent studies indicate tight crosstalk between stress and autophagy in liver *** the bal-ance between damage and autophagy is broken,autophagy can no longer resist injury or main-tain *** recent years,FGF21(fibroblast growth factor 21)-induced autophagy has attracted much ***21 is regarded as a stress hormone and can be up-regulated by an abundance of signaling pathways in response to ***,increased FGF21 activates autophagy by a complicated signaling network in which mTOR plays a pivotal *** review summarizes the mechanism of FGF21-mediated autophagy and its derived application in the defense of stress in liver diseases and offers a glimpse into its promising prospect in future clinical practice.

关键词： Autophagy Fibroblast growth factor 21 Liver diseases mTOR Stress

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Validation and performance of three scoring systems for predicting primary non-function and early allograft failure after liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2024年第5期23卷 463-471页

作者： Yu Nie Jin-Bo Huang Shu-Jiao He Hua-Di Chen Jun-Jun Jia Jing-Jing Li Xiao-Shun He Qiang Zhao General Surgery Center Department of Hepatobiliary Surgery IIResearch Center for Artificial Organ and Tissue EngineeringGuangzhou Clinical Research and Transformation Center for Artificial LiverInstitute of Regenerative MedicineZhujiang HospitalSouthern Medical UniversityGuangzhou 510515China organ transplant Center the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Guangdong Provincial Key Laboratory of organ Donation and transplant Immunology Guangzhou 510080China Guangdong Provincial International Cooperation Base of Science and Technology Guangzhou 510080China Division of Hepatobiliary Pancreatic Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Background: Primary non-function(PNF) and early allograft failure(EAF) after liver transplantation(LT) seriously affect patient outcomes. In clinical practice, effective prognostic tools for early identifying recipients at high risk of PNF and EAF were urgently needed. Recently, the Model for Early Allograft Function(MEAF), PNF score by King's College(King-PNF) and Balance-and-Risk-Lactate(BAR-Lac) score were developed to assess the risks of PNF and EAF. This study aimed to externally validate and compare the prognostic performance of these three scores for predicting PNF and EAF. Methods: A retrospective study included 720 patients with primary LT between January 2015 and December 2020. MEAF, King-PNF and BAR-Lac scores were compared using receiver operating characteristic(ROC) and the net reclassification improvement(NRI) and integrated discrimination improvement(IDI) analyses. Results: Of all 720 patients, 28(3.9%) developed PNF and 67(9.3%) developed EAF in 3 months. The overall early allograft dysfunction(EAD) rate was 39.0%. The 3-month patient mortality was 8.6% while 1-year graft-failure-free survival was 89.2%. The median MEAF, King-PNF and BAR-Lac scores were 5.0(3.5–6.3),-2.1(-2.6 to-1.2), and 5.0(2.0–11.0), respectively. For predicting PNF, MEAF and King-PNF scores had excellent area under curves(AUCs) of 0.872 and 0.891, superior to BAR-Lac(AUC = 0.830). The NRI and IDI analyses confirmed that King-PNF score had the best performance in predicting PNF while MEAF served as a better predictor of EAD. The EAF risk curve and 1-year graft-failure-free survival curve showed that King-PNF was superior to MEAF and BAR-Lac scores for stratifying the risk of EAF. Conclusions: MEAF, King-PNF and BAR-Lac were validated as practical and effective risk assessment tools of PNF. King-PNF score outperformed MEAF and BAR-Lac in predicting PNF and EAF within 6 months. BAR-Lac score had a huge advantage in the prediction for PNF without post-transplant variables. Proper use

关键词： Primary non-function Early allograft failure Risk predicting model Liver transplantation

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Influence of sex on outcomes of liver transplantation for hepatocellular carcinoma:a multicenter cohort study in China

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Cancer Biology & Medicine 2024年第4期21卷 347-362页

作者： Jian Chen Zhe Yang Fengqiang Gao Zhisheng Zhou Junli Chen Di Lu Kai Wang Meihua Sui Zhengxin Wang Wenzhi Guo Guoyue Lyu Haizhi Qi Jinzhen Cai Jiayin Yang Shusen Zheng Xiao Xu Zhejiang University School of Medicine Hangzhou 310030China institute of organ transplantation Zhejiang UniversityHangzhou 310030China Department of Hepatobiliary and Pancreatic Surgery Shulan Hospital of HangzhouHangzhou 310006China National Center for Healthcare Quality Management in Liver transplant Hangzhou 310003China Department of General Surgery Huashan HospitalFudan UniversityShanghai 200040China Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Hepatobiliary and Pancreatic Surgery The First Hospital of Jilin UniversityChangchun 130021China Department of Liver transplantation Second Xiangya HospitalCentral South UniversityChangsha 410008China Department of organ transplantation Center The Affiliated Hospital of Qingdao UniversityQingdao 266003China Department of Liver Surgery and Liver transplantation Center West China HospitalSichuan UniversityChengdu 610044China NHC Key Laboratory of Combined multi-organ transplantation Hangzhou 310003China Department of Hepatobiliary and Pancreatic Surgery The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Objective:Sex-specific differences are observed in various liver diseases,but the influence of sex on the outcomes of hepatocellular carcinoma(HCC)after liver transplantation(LT)remains to be *** study is the first Chinese nationwide investigation of the role of sex in post-LT outcomes in patients with ***:Data for recipients with HCC registered in the China Liver transplant Registry between January 2015 and December 2020 were *** associations between donor,recipient,or donor-recipient transplant patterns by sex and the post-LT outcomes were studied with propensity score matching(PSM).The survival associated with different sex-based donor-recipient transplant patterns was further ***:Among 3,769 patients enrolled in this study,the 1-,3-,and 5-year overall survival(OS)rates of patients with HCC after LT were 96.1%,86.4%,and 78.5%,respectively,in female recipients,and 95.8%,79.0%,and 70.7%,respectively,in male recipients after PSM(P=0.009).However,the OS was comparable between recipients with female donors and male *** analysis indicated that male recipient sex was a risk factor for post-LT survival(HR=1.381,P=0.046).Among the donor-recipient transplant patterns,the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival(Ptransplant pattern was associated with the poorest post-LT *** from male donors may provide the most benefit to female *** results indicate that sex should be considered as a critical factor in organ allocation.

关键词： Sex liver transplantation hepatocellular carcinoma outcome recipient donor

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Hepatic vein reconstruction during hepatectomy:A feasible and underused technique

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 421-427页

作者： Manish Ahuja Kunal Joshi Chris Coldham Paulo Muiesan Bobby Dasari Manuel Abradelo Ravi Marudanayagam Darius Mirza John Isaac David Bartlett Nikolaos A Chatzizacharias Robert P Sutcliffe Keith J Roberts Department of HPB and Liver transplant Surgery University Hospitals Birmingham NHS Foundation TrustBirminghamUK institute of Immunology and Immunotherapy University of BirminghamBirminghamUK

Complete surgical resection(R0)of liver tumors,primary or metastatic,remains the main objective in management of primary and metastatic liver tumors[1].Tumors invading to the proximity of the hepatic venous outflow pose a peculiar challenge to achieve R0 resections,because this location may render a tumor *** median survival of patients with liver tumor without surgery is less than 12 months[2].Even with surgery,post-hepatectomy liver failure and subsequently increased mortality are the main problems associated with complex resection[3].Moreover,when the vein is affected,vein resection and subsequent reconstruction are *** resection is a standard practice in liver resection and transplantation[4],for example,hepatic vein reconstruction during a living-donor liver transplant,porto-mesenteric axis reconstruction during resection of advanced pancreatic cancer and caval reconstruction during resection of retroperitoneal ***,novel techniques like total hepatic vascular exclusion(HVE)[5],veno-venous bypass[6]and ex vivo hepatic resection[7,8]have facilitated curative resections of tumors close to one or more major hepatic veins.

关键词： hepatectomy surgery mortality

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Clinical application of COVID-19 vaccine in liver transplant recipients

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 339-343页

作者： Feng-Chao Liu Man Xie Wei Rao Division of Hepatology Liver Disease CenterThe Affiliated Hospital of Qingdao UniversityQingdao 266000China organ transplantation Center The Affiliated Hospital of Qingdao UniversityQingdao 266000China institute of organ Donation and transplantation of Qingdao University Qingdao 266000China Department of Gastroenterology The Affiliated Hospital of Qingdao UniversityQingdao 266000China

Background:Solid organ transplant(SOT)activities,such as liver transplant,have been greatly influenced by the pandemic of coronavirus disease 2019(COVID-19),a disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Immunosuppressed individuals of liver transplant recipients(LTRs)tend to have a high risk of COVID-19 infection and related ***,COVID-19 vaccination has been recommended to be administered as early as possible in *** sources:The keywords“liver transplant”,“SARS-CoV-2”,and“vaccine”were used to retrieve articles published in ***:The antibody response following the 1st and 2nd doses of vaccination was disappointingly low,and the immune responses among LTRs remarkably improved after the 3rd or 4th dose of *** the 3rd or 4th dose of COVID-19 vaccine increased the antibody titer,a proportion of patients remained ***,recent studies showed that SARS-CoV-2 vaccine could trigger adverse events in LTRs,including allograft rejection and liver ***:This review provides the recently reported data on the antibody response of LTRs following various doses of vaccine,risk factors for poor serological response and adverse events after vaccination.

关键词： Liver transplant COVID-19 SARS-CoV-2 Vaccine Antibody response

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Mitochondrial dysfunction affects hepatic immune and metabolic remodeling in patients with hepatitis B virus-related acute-onchronic liver failure

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World Journal of Gastroenterology 2024年第8期30卷 881-900页

作者： Yu Zhang Xiao-Ling Tian Jie-Qun Li Dong-Sheng Wu Qiang Li Bin Chen Department of Hepatology Institute of HepatologyThe First Affiliated Hospital of Hunan University of Chinese MedicineChangsha 410021Hunan ProvinceChina Department of Liver transplant Transplant Medical Research CenterThe Second Xiangya Hospital of Central South UniversityChangsha 410011Hunan ProvinceChina Department of Surgery The First Affiliated Hospital of Hunan University of Chinese MedicineChangsha 410021Hunan ProvinceChina

BACKGROUND Immune dysregulation and metabolic derangement have been recognized as key factors that contribute to the progression of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF).However,the mechanisms underlying immune and metabolic derangement in patients with advanced HBV-ACLF are *** To identify the bioenergetic alterations in the liver of patients with HBV-ACLF causing hepatic immune dysregulation and metabolic *** Liver samples were collected from 16 healthy donors(HDs)and 17 advanced HBV-ACLF patients who were eligible for liver *** mitochondrial ultrastructure,metabolic characteristics,and immune microenvironment of the liver were *** focus was given to organic acid metabolism as well as the function and subpopulations of macrophages in patients with *** Compared with HDs,there was extensive hepatocyte necrosis,immune cell infiltration,and ductular reaction in patients with *** patients,the liver suffered severe hypoxia,as evidenced by increased expression of hypoxia-inducible factor-1α.Swollen mitochondria and cristae were observed in the liver of *** number,length,width,and area of mitochondria were adaptively increased in *** metabolomics analysis revealed that mitochondrial oxidative phosphorylation decreased,while anaerobic glycolysis was enhanced in patients with *** findings suggested that,to a greater extent,hepa-tocytes used the extra-mitochondrial glycolytic pathway as an energy *** with HBV-ACLF had elevated levels of chemokine C-C motif ligand 2 in the liver homogenate,which stimulates peripheral monocyte infiltration into the *** and functional analysis of macrophage subsets revealed that patients with ACLF had a high abundance of CD68^(+)HLA-DR^(+)macrophages and elevated levels of both interleukin-1βand transforming growth factor-β1 in their *** abundance of CD206^(+)CD163^(+)macrophag

关键词： Acute-on-chronic liver failure Hypoxia-inducible factor-1α Mitochondria Metabolic phenotype Immune cells

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Role of incretins and glucagon receptor agonists in metabolic dysfunction-associated steatotic liver disease:Opportunities and challenges

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World Journal of Hepatology 2024年第5期16卷 731-750页

作者： Chencheng Xie Naim Alkhouri Mohamed A Elfeki Department of Internal Medicine University of South Dakota Sanford School of MedicineSioux FallsSD 57105United States Department of Hepatology Avera Mckennan University Hospital and Transplant InstituteSioux FallsSD 57105United States Department of Hepatology Arizona Liver HealthChandlerAZ 85712United States Department of Hepatology Avera McKennan University Hospital and Transplant InstituteSioux FallsSD 57105United States

Metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most common chronic liver disease worldwide,paralleling the rising pandemic of obesity and type 2 *** to the growing global health burden and com-plex pathogenesis of MASLD,a multifaceted and innovative therapeutic approach is *** receptor agonists,which were initially developed for diabetes management,have emerged as promising candidates for MASLD *** review describes the pathophysiological mechanisms and action sites of three major classes of incretin/glucagon receptor agonists:glucagon-like peptide-1 receptor agonists,glucose-dependent insulinotropic polypeptide receptor agonists,and glucagon receptor *** and glucagon directly or indirectly impact various organs,including the liver,brain,pancreas,gastro-intestinal tract,and adipose ***,these agents significantly improve glycemic control and weight management and mitigate MASLD ***,this study provides a summary of clinical trials analyzing the effect-iveness and safety of incretin receptor agonists in MASLD management and provides an in-depth analysis highlighting their beneficial effects on improving liver function,hepatic steatosis,and intrahepatic *** are emerging challenges associated with the use of these medications in the real world,particularly adverse events,drug-drug interactions,and barriers to access,which are discussed in ***,this review highlights the evolving role of incretin receptor agonists in MASLD management and suggests future research directions.

关键词： Metabolic dysfunction-associated steatotic liver disease Metabolic dysfunction-associated steatohepatitis Glucagon-like peptide-1 Glucose-dependent inulinotropic polypeptide Glucagon Incretin Receptor agonist

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National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma

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World Journal of Gastroenterology 2024年第9期30卷 1018-1042页

作者： Faisal Saud Dar Zaigham Abbas Irfan Ahmed Muhammad Atique Usman Iqbal Aujla Muhammad Azeemuddin Zeba Aziz Abu Bakar Hafeez Bhatti Tariq Ali Bangash Amna Subhan Butt Osama Tariq Butt Abdul Wahab Dogar Javed Iqbal Farooqi Faisal Hanif Jahanzaib Haider Siraj Haider Syed Mujahid Hassan Adnan Abdul Jabbar Aman Nawaz Khan Muhammad Shoaib Khan Muhammad Yasir Khan Amer Latif Nasir Hassan Luck Ahmad Karim Malik Kamran Rashid Sohail Rashid Mohammad Salih Abdullah Saeed Amjad Salamat Ghias-un-Nabi Tayyab Aasim Yusuf Haseeb Haider Zia Ammara Naveed Department of Hepatopancreatic Biliary Surgery&Liver transplant Pakistan Kidney and Liver Institute&Research CentreLahore 54000Pakistan Department of Hepatogastroenterology and Liver transplantation Dr.Ziauddin University HospitalKarachi 75600SindhPakistan University of Aberdeen Aberdeen B243FXUnited Kingdom Department of Pathology Pakistan Kidney and Liver Institute&Research CentreLahore 54000Pakistan Department of Gastroenterology&Hepatology Pakistan Kidney and Liver Institute&Research CentreLahore 54000Pakistan Department of Radiology Aga Khan UniversityKarachi 74800Pakistan Department of Oncology Hameed Latif HospitalLahore 54000Pakistan Division of Hepatopancreatic Biliary Surgery&Liver transplantation Shifa International HospitalIslamabad 44000Pakistan Department of Hepatopancreatic Biliary Surgery&Liver transplant Shaikh Zayed Hospital and Post Graduate Medical InstituteLahore 54000Pakistan Department of Medicine Aga Khan University HospitalKarachi 74800Pakistan Department of Liver transplant Pir Abdul Qadir Shah Jeelani Institute of Medical SciencesGambat 66020Pakistan Department of Medicine&Gastroenterology Lifecare Hospital and Research CentrePeshawar 25000Khyber PakhtunkhwaPakistan Department of Hepatopancreatobiliary&Liver transplant Bahria International HospitalLahore 54000Pakistan Department of Surgery Hepatopancreatobiliary&Liver TransplantDow University of Health SciencesKarachi 74800Pakistan Department of Gastroenterology Hepatology&NutritionPir Abdul Qadir Shah Jeelani Institute of Medical SciencesGambat 66020Pakistan Department of Oncology Dr.Ziauddin HospitalKarachi 74800Pakistan Department of Radiology Rehman Medical InstitutePeshawar 25000Pakistan Army Liver transplant Unit Pak Emirates Military HospitalRawalpindi 46000Pakistan Department of Gastroenterology Sindh Institute of Urology and TransplantationKarachi 75500Pakistan Rashid Nursing Home and Cancer Clinic Rashid Nursing Home and Cancer ClinicRawalpindi 46000Pakistan Department of Gastroentero

A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26,2023,at the Pakistan Kidney and Liver institute&Research Centre(PKLI&RC)after initial consultations with the *** Pakistan Society for the Study of Liver Diseases(PSSLD)and PKLI&RC jointly organised this *** effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma(hCCA).The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these *** coordinated effort can minimise delays and give patients a chance for curative treatment and effective *** diagnostic and staging workup includes high-quality computed tomography,magnetic resonance imaging,and magnetic resonance *** cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for ***,histopathologic confirmation is not always required before *** ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for *** only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette *** patients with unresectable hCCA can be considered for liver *** chemotherapy should be offered to patients with a high risk of *** use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary *** with acute cholangitis can be drained with endoscopic or percutaneous biliary *** chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.

关键词： Hilar cholangiocarcinoma Bismuth-Corlette classification Memorial Sloan Kettering Cancer Centre Staging Preoperative biliary drainage Portal vein embolisation Surgical resection Hepatectomy

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