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liver transplantation for hepatocellular carcinoma in India: Are we ready for 2040?

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World Journal of transplantation 2024年第1期14卷 141-153页

作者： Hirak Pahari Amruth Raj Ambreen Sawant Dipak S Ahire Raosaheb Rathod Chetan Rathi Tushar Sankalecha Sachin Palnitkar Vikram Raut department of liver transplant and hpb Surgery Medicover HospitalsNavi Mumbai 410210MaharashtraIndia department of liver transplant Anaesthesia Medicover HospitalsNavi Mumbai 410210MaharashtraIndia department of Gastroenterology and Hepatology Medicover HospitalsNavi Mumbai 410210India department of Gastroenterology and Hepatology Medicover HospitalsNavi Mumbai 410210MaharashtraIndia department of Gastroenterology and Hepatology Medicover HospitalsAurangabad 431003India department of Gastroenterology and Hepatology Medicover HospitalsNashik 422009India department of Gastroenterology and Hepatology Medicover HospitalsPune 411026India

BACKGROUND liver transplantation(LT)for hepatocellular carcinoma(HCC)has been widely researched and is well established worldwide.The cornerstone of this treatment lies in the various criteria formulated by expert consensus and experience.The variations among the criteria are staggering,and the short-and long-term outcomes are controversial.AIM To study the differences in the current practices of LT for HCC at different centers in India and discuss their clinical implications in the future.METHODS We conducted a survey of major centers in India that performed LT in December 2022.A total of 23 responses were received.The centers were classified as high-and low-volume,and the current trend of care for patients undergoing LT for HCC was noted.RESULTS Of the 23 centers,35%were high volume center(>500 liver transplants)while 52%were high-volume centers that performed more than 50 transplants/year.Approximately 39%of centers had performed>50 LT for HCC while the percent distribution for HCC in LT patients was 5%–15%in approximately 73%of the patients.Barring a few,most centers were divided equally between University of California,San Francisco(UCSF)and center-specific criteria when choosing patients with HCC for LT,and most(65%)did not have separate transplant criteria for deceased donor LT and living donor LT(LDLT).Most centers(56%)preferred surgical resection over LT for a Child A cirrhosis patient with a resectable 4 cm HCC lesion.Positron-emission tomography-computed tomography(CT)was the modality of choice for metastatic workup in the majority of centers(74%).Downstaging was the preferred option for over 90%of the centers and included transarterial chemoembolization,transarterial radioembolization,stereotactic body radiotherapy and atezolizumab/bevacizumab with varied indications.The alphafetoprotein(AFP)cut-off was used by 74%of centers to decide on transplantation as well as to downstage tumors,even if they met the criteria.The criteria for successful downstaging varied,but most centers conformed to the UCSF or

关键词： Hepatocellular carcinoma liver transplant India Downstaging Survey Milan University of California,San Francisco Portal vein tumor thrombus Expanded criteria

Navigating the controversy regarding antibiotic prophylaxis in acute variceal bleeding

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World Journal of Gastroenterology 2024年第18期30卷 2485-2487页

作者： David Aguirre-Villarreal Ignacio García-Juárez department of Gastroenterology and liver transplant Unit Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico City 14080Mexico

Antibiotic prophylaxis in patients with cirrhosis and acute variceal bleeding is part of the standard of care according to most clinical guidelines.However,with recent evidence arguing against antibiotic prophylaxis,t... 详细信息

关键词： Cirrhosis Acute variceal bleeding Antibiotic prophylaxis Endoscopic band ligation Spontaneous bacterial peritonitis

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 experts.The Pakistan Society for the Study of liver Diseases(PSSLD)and PKLI&RC jointly organised this meeting.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 patients.This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation.The diagnostic and staging workup includes high-quality computed tomography,magnetic resonance imaging,and magnetic resonance cholangiopancreato-graphy.Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis.However,histopathologic confirmation is not always required before resection.Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging.The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification.Selected patients with unresectable hCCA can be considered for liver transplantation.Adjuvant chemotherapy should be offered to patients with a high risk of recurrence.The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions.Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage.Palliative 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

Role of gut-liver axis and glucagon-like peptide-1 receptor agonists in the treatment of metabolic dysfunction-associated fatty liver disease

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World Journal of Gastroenterology 2024年第23期30卷 2964-2980页

作者： Jakub Rochoń Piotr Kalinowski Ksenia Szymanek-Majchrzak MichałGrąt department of General Transplant and Liver SurgeryMedical University of WarsawWarsaw 02-097Poland department of Medical Microbiology Medical University of WarsawWarsaw 02-004Poland

Metabolic dysfunction-associated fatty liver disease(MAFLD)is a hepatic manifestation of the metabolic syndrome.It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most countries.MAFLD is a progressive disease with the most severe cases presenting as advanced fibrosis or cirrhosis with an increased risk of hepatocellular carcinoma.Gut microbiota play a significant role in the pathogenesis and progression of MAFLD by disrupting the gut-liver axis.The mechanisms involved in maintaining gut-liver axis homeostasis are complex.One critical aspect involves preserving an appropriate intestinal barrier permeability and levels of intestinal lumen metabolites to ensure gutliver axis functionality.An increase in intestinal barrier permeability induces metabolic endotoxemia that leads to steatohepatitis.Moreover,alterations in the absorption of various metabolites can affect liver metabolism and induce liver steatosis and fibrosis.Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)are a class of drugs developed for the treatment of type 2 diabetes mellitus.They are also commonly used to combat obesity and have been proven to be effective in reversing hepatic steatosis.The mechanisms reported to be involved in this effect include an improved regulation of glycemia,reduced lipid synthesis,β-oxidation of free fatty acids,and induction of autophagy in hepatic cells.Recently,multiple peptide receptor agonists have been introduced and are expected to increase the effectiveness of the treatment.A modulation of gut microbiota has also been observed with the use of these drugs that may contribute to the amelioration of MAFLD.This review presents the current understanding of the role of the gutliver axis in the development of MAFLD and use of members of the GLP-1 RA family as pleiotropic agents in the treatment of MAFLD.

关键词： Metabolic dysfunction-associated fatty liver disease Metabolic dysfunction-associated steatohepatitis Nonalcoholic fatty liver disease Non-alcoholic steatohepatitis Metabolic syndrome Obesity Gastrointestinal microbiota Glucagon-like peptide-1 Glucagon-like peptide-2 Bariatric surgery

Incidence,Risk Factors,and Prognosis of Patients with Hepatocellular Carcinoma and Brain Metastases

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Current Medical Science 2024年第1期44卷 180-186页

作者： Jin-cheng FENG Ying HE Georgios Polychronidis Jian XIN Shen YOU Jun XIONG department of liver transplantation Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China Key Laboratory of transplant Engineering and Immunology Laboratory of Liver TransplantationFrontiers Science Center for Disease-Related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041China department of General Visceral and Transplant SurgeryUniversity of HeidelbergIm Neuenheimer Feld 110Heidelberg 69120Germany department of Hepatobiliary and Pancreatic Surgery Fujian Provincial HospitalFuzhou 350001China

Objective Brain metastases significantly impact the clinical course of patients with hepatocellular carcinoma(HCC).This study aimed to examine the age-related incidence,demographics,and survival of patients with HCC and brain metastases.Methods Data of HCC patients from 2010 to 2015 in the Surveillance,Epidemiology,and End Results(SEER)Registry were screened for the presence of brain metastases.They were stratified by age and ethnicity.Multivariable logistic and Cox regression analyses were used to identify factors associated with brain metastases and those with overall survival(OS)and liver cancer-specific survival(CSS),respectively.Results A total of 141 HCC patients presenting with brain metastases were identified,accounting for 0.35% of all HCC patients and 2.37% of patients with metastatic disease.Among all HCC patients,the incidence rate was the highest among patients aged 30-49 years old(0.47%).Ethnicity was not associated with the presence of brain metastases at the time of HCC diagnosis.However,African-American patients presented with a significantly lower disease-specific survival[median time:1 month;interquartile range(IQR):0-3.0 months].Initial lung or bone metastasis was independently associated with an increased risk of the presence of brain metastases[odds ratio(OR):12.62,95% confidence interval(CI):8.40-18.97]but was not associated with a worse OS or CSS among those with brain metastases.Conclusion This study identified the age-related incidence and risk factors of brain metastases in HCC patients.These results may contribute to the consideration of brain screening among patients with initial metastatic HCC with lung or bone metastases,and influence the counseling of this patient population regarding their prognosis.

关键词： brain metastases hepatocellular carcinoma age-related incidence cancer-specific survival overall survival

Relative carcinogenicity of tacrolimus vs mycophenolate after solid organ transplantation and its implications for liver transplant care

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World Journal of Hepatology 2024年第4期16卷 650-660页

作者： Dorothy Liu Mark M Youssef Josephine A Grace Marie Sinclair department of Gastroenterology Austin HealthMelbourne 3084VictoriaAustralia Victorian liver transplant Unit Austin HealthMelbourne 3084VictoriaAustralia department of Medicine University of MelbourneMelbourne 3084VictoriaAustralia

BACKGROUND De novo malignancy is a leading cause of late morbidity and mortality in liver transplant recipients.Cumulative immunosuppression has been shown to contribute to post-transplant malignancy(PTM)risk.There is emerging evidence on the differential carcinogenic risk profile of individual immunosuppressive drugs,independent of the net effect of immunosuppression.Calcineurin inhibitors such as tacrolimus may promote tumourigenesis,whereas mycophenolic acid(MPA),the active metabolite of mycophenolate mofetil,may limit tumour progression.liver transplantation(LT)is relatively unique among solid organ transplantation in that immunosuppression monotherapy with either tacrolimus or MPA is often achievable,which makes careful consideration of the risk-benefit profile of these immunosuppression agents particularly relevant for this cohort.However,there is limited clinical data on this subject in both LT and other solid organ transplant recipients.AIM To investigate the relative carcinogenicity of tacrolimus and MPA in solid organ transplantation.METHODS A literature search was conducted using MEDLINE and Embase databases using the key terms“solid organ transplantation”,“tacrolimus”,“mycophenolic acid”,and“carcinogenicity”,in order to identify relevant articles published in English between 1st January 2002 to 11th August 2022.Related terms,synonyms and explosion of MeSH terms,Boolean operators and truncations were also utilised in the search.Reference lists of retrieved articles were also reviewed to identify any additional articles.Excluding duplicates,abstracts from 1230 records were screened by a single reviewer,whereby 31 records were reviewed in detail.Full-text articles were assessed for eligibility based on pre-specified inclusion and exclusion criteria.RESULTS A total of 6 studies were included in this review.All studies were large population registries or cohort studies,which varied in transplant era,type of organ transplanted and immunosuppression protocol used.Overall,there was no clear difference demonst

关键词： Immunosuppression Solid organ transplantation liver transplantation Carcinogenicity Tacrolimus Mycophenolate

Pancreatic neuroendocrine tumors:Are tumors smaller than 2 cm truly indolent?

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1756-1762页

作者： Sergio Hoyos Pablo Posada-Moreno Natalia Guzman-Arango Romario Chanci-Drago Jaime Chavez Alvaro Andrés-Duarte Santiago Salazar-Ochoa Hepatobilary and liver transplant Unit Hospital Pablo Tobon Uribe and Gastrohepathology Group Universidad de AntioquiaMedellin 050034AntioquiaColombia department of General Surgery Universidad Pontificia BolivarianaMedellín 050034AntioquiaColombia

BACKGROUND Pancreatic neuroendocrine tumors(PNETs)are relatively rare but rank as the second most common pancreatic neoplasm.They can be functional,causing early metabolic disturbances due to hormone secretion,or non-functional and diagnosed later based on tumor size-related symptoms.Recent diagnoses of PNETs under 2 cm in size have sparked debates about their management;some practitioners advocate for surgical removal and others suggest observation due to the tumors’lower potential for malignancy.However,it is unclear whether managing these small tumors expectantly is truly safe.AIM To evaluate poor prognostic factors in PNETs based on tumor size(>2 cm ordepartment.Qualitative variables were described using absolute and relative frequencies,and quantitative variables were expressed using measures of central tendency and their corresponding measures of dispersion.RESULTS The presence of lymph node involvement,neural involvement,and lymphovascular invasion were all associated with an increased risk of mortality,with hazard ratios of 5.68(95%CI:1.26–25.61,P=0.024),6.44(95%CI:1.43–28.93,P=0.015),and 24.87(95%CI:2.98–207.19,P=0.003),respectively.Neural involvement and lymphovascular invasion were present in tumors smaller than 2 cm in diameter and those larger than 2 cm in diameter.The recurrence rates between the two tumor groups were furthermore similar:18.2%for tumors smaller than 2 cm and 21.4%for tumors larger than 2 cm.Patient survival was additionally comparable between the two tumor groups.CONCLUSION Tumor size does not dictate prognosis;lymph node and lymphovascular involvement affect mortality,which high-lights that histopath

关键词： Neuroendocrine tumor Pancreatic neoplasm Pancreas Pancreatic neuroendocrine neoplasm Pancreatic neuroendocrine tumors

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 unclear.AIM To identify the bioenergetic alterations in the liver of patients with HBV-ACLF causing hepatic immune dysregulation and metabolic disorders.METHODS liver samples were collected from 16 healthy donors(HDs)and 17 advanced HBV-ACLF patients who were eligible for liver transplantation.The mitochondrial ultrastructure,metabolic characteristics,and immune microenvironment of the liver were assessed.More focus was given to organic acid metabolism as well as the function and subpopulations of macrophages in patients with HBV-ACLF.RESULTS Compared with HDs,there was extensive hepatocyte necrosis,immune cell infiltration,and ductular reaction in patients with ACLF.In 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 patients.The number,length,width,and area of mitochondria were adaptively increased in hepatocytes.Targeted metabolomics analysis revealed that mitochondrial oxidative phosphorylation decreased,while anaerobic glycolysis was enhanced in patients with HBV-ACLF.These findings suggested that,to a greater extent,hepa-tocytes used the extra-mitochondrial glycolytic pathway as an energy source.Patients with HBV-ACLF had elevated levels of chemokine C-C motif ligand 2 in the liver homogenate,which stimulates peripheral monocyte infiltration into the liver.Characterization 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 livers.The abundance of CD206^(+)CD163^(+)macrophages and expression of interleukin-10 decreased.Th

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

Hepatolithiasis:Epidemiology,presentation,classification and management of a complex disease

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World Journal of Gastroenterology 2024年第13期30卷 1836-1850页

作者： Rodrigo V.Motta Francesca Saffioti Vasileios K Mavroeidis Translational Gastroenterology and liver Unit Nuffield Department of MedicineUniversity of OxfordOxford OX39DUUnited Kingdom department of Gastroenterology and Hepatology Oxford University Hospitals NHS Foundation TrustJohn Radcliffe HospitalOxford OX39DUUnited Kingdom UCL Institute for liver and Digestive Health and Sheila Sherlock liver Unit Royal Free Hospital and University College LondonLondon NW32QGUnited Kingdom department of hpb Surgery Bristol Royal InfirmaryUniversity Hospitals Bristol and Weston NHS Foundation TrustBristol BS28HWUnited Kingdom department of transplant Surgery North Bristol NHS TrustSouthmead HospitalBristol BS105NBUnited Kingdom department of Gastrointestinal Surgery North Bristol NHS TrustSouthmead HospitalBristol BS105NBUnited Kingdom

The term hepatolithiasis describes the presence of biliary stones within the intrahepatic bile ducts,above the hilar confluence of the hepatic ducts.The disease is more prevalent in Asia,mainly owing to socioeconomic and dietary factors,as well as the prevalence of biliary parasites.In the last century,owing to migration,its global incidence has increased.The main pathophysiological mechanisms involve cholangitis,bile infection and biliary strictures,creating a self-sustaining cycle that perpetuates the disease,frequently characterised by recurrent episodes of bacterial infection referred to as syndrome of“recurrent pyogenic cholangitis”.Furthermore,long-standing hepatolithiasis is a known risk factor for development of intrahepatic cholangiocarcinoma.Various classifications have aimed at providing useful insight of clinically relevant aspects and guidance for treatment.The management of symptomatic patients and those with complications can be complex,and relies upon a multidisciplinary team of hepatologists,endoscopists,interventional radiologists and hepatobiliary surgeons,with the main goal being to offer relief from the clinical presentations and prevent the development of more serious complications.This comprehensive review provides insight on various aspects of hepatolithiasis,with a focus on epidemiology,new evidence on pathophysiology,most important clinical aspects,different classification systems and contemporary management.

关键词： Cholelithiasis Intrahepatic stones Cholangiocarcinoma Biliary parasites Recurrent pyogenic cholangitis Oriental cholangiohepatitis Hepatectomy Cholangioscopy liver transplant Paediatric