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

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 *** cornerstone of this treatment lies in the various criteria formulated by expert consensus and *** variations among the criteria are staggering,and the short-and long-term outcomes are *** To study the differences in the current practices of LT for HCC at different centers in India and discuss their clinical implications in the *** We conducted a survey of major centers in India that performed LT in December 2022.A total of 23 responses were *** centers were classified as high-and low-volume,and the current trend of care for patients undergoing LT for HCC was *** Of the 23 centers,35%were high volume center(>500 liver transplants)while 52%were high-volume centers that performed more than 50 transplants/*** 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 *** 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 ***-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 *** 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 for successful downstaging v

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

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Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio:Markers predicting immune-checkpoint inhibitor efficacy and immune-related adverse events

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 577-582页

作者： Qiu-Yu Jiang Ru-Yi Xue department of Gastroenterology and hepatology Zhongshan HospitalShanghai Institute of Liver DiseaseFudan UniversityShanghai 200032China department of Gastroenterology and hepatology Shanghai Baoshan District Wusong Central Hospital(Zhongshan Hospital Wusong BranchFudan University)Shanghai 200940China

We conducted a comprehensive review of existing prediction models pertaining to the efficacy of immune-checkpoint inhibitor(ICI)and the occurrence of immune-related adverse events(irAEs).The predictive potential of neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)in determining ICI effectiveness has been extensively investigated,while limited research has been conducted on predicting ***,the combined model incor-porating NLR and PLR,either with each other or in conjunction with additional markers such as carcinoembryonic antigen,exhibits superior predictive capabilities compared to individual markers *** and PLR are promising markers for clinical *** models ought to incorporate established efficacious models and newly identified ones,thereby constituting a multifactor composite ***,efforts should be made to explore effective clinical application approaches that enhance the predictive accuracy and efficiency.

关键词： Neutrophil-to-lymphocyte ratio Platelet-to-lymphocyte ratio Immunecheckpoint inhibitor Immune-related adverse event

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Direct-acting antivirals failed to reduce the incidence of hepatocellular carcinoma occurrence in hepatitis C virus associated cirrhosis: A real-world study

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World Journal of hepatology 2024年第1期16卷 41-53页

作者： Xue-Mei Tao Ming-Hui Zeng You-Fei Zhao Jia-Xin Han Yu-Qiang Mi Liang Xu Clinical School of the Second People’s Hospital Tianjin Medical UniversityTianjin 300192China department of hepatology Tianjin Second People’s HospitalTianjin 300192China department of hepatology Tianjin Research Institute of Liver DiseasesTianjin 300192China

BACKGROUND Direct-acting antivirals(DAAs)revolutionized the treatment of chronic hepatitis C virus(HCV)-associated disease achieving high rates of sustained virological response(SVR).However,whether DAAs can reduce the occurrence of hepatocellular carcinoma(HCC)in patients with HCV-associated cirrhosis who are at high risk have not been *** To investigate the effect of DAAs on the occurrence of HCC in patients with HCVassociated cirrhosis after achieving *** Of 427 inpatients with HCV-associated cirrhosis were enrolled in Tianjin Second People's Hospital from January 2014 to April 2020.118 patients weren’t received antiviral treatment with any reasons named non-antiviral treatment group,and 236 patients obtained from the 309 DAAs treatment patients according to the propensity score matching named DAAs treatment *** information and laboratory data were collected from baseline and the following ***-Meier curve and Log-Rank test were used to compare the incidence and cumulative incidence of HCC between the two *** proportional risk regression was used to re-evaluate the risk factors for *** HCC incidence was 4.68/100PY(95%CI,3.09-6.81)in the DAAs treatment group,while it was 3.00/100PY(95%CI,1.50-5.37)in the non-antiviral treatment group,and the relative risk was 1.82(95%CI,0.93-3.53,P>0.05).The incidence of HCC at 12,24,36 and 48 months was 3.39%,6.36%,8.47%and 10.17%in the DAAs treatment group,and it was 0%,0%,3.39%and 9.32%in the non-antiviral treatment group,***>58[hazard ratio(HR)=1.089;95%CI,1.033-1.147;P=0.002]and liver stiffness measurement>27.85 kPa(HR=1.043;95%CI,1.022-1.065;P=0.000)were risk factors for HCC in all patients(n=427),and DAAs treatment didn’t show protective *** DAAs treatment seems failed to reduce the incidence of HCC occurrence in HCV-associated cirrhosis in 48 months,and even increased the incidence of HCC in 36 months.

关键词： Direct-acting antivirals Sustained viral response Cirrhosis Hepatocellular carcinoma Risk factor

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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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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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LONP1 ameliorates liver injury and improves gluconeogenesis dysfunction in acute-on-chronic liver failure

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Chinese Medical Journal 2024年第2期137卷 190-199页

作者： Muchen Wu Jing Wu Kai Liu Minjie Jiang Fang Xie Xuehong Yin Jushan Wu Qinghua Meng department of liver Disease Beijing You-An HospitalCapital Medical UniversityBeijing 100069China Beijing Institute of hepatology Beijing You-An HospitalCapital Medical UniversityBeijing 100069China department of General Surgery Beijing You-An HospitalCapital Medical UniversityBeijing 100069China

Background:Acute-on-chronic liver failure(ACLF)is a severe liver disease with complex *** hypoglycemia is common in patients with ACLF and often predicts a worse *** evidence suggests that glucose metabolic disturbance,especially gluconeogenesis dysfunction,plays a critical role in the disease progression of *** protease-1(LONP1)is a novel mediator of energy and glucose ***,whether gluconeogenesis is a potential mechanism through which LONP1 modulates ACLF remains ***:In this study,we collected liver tissues from ACLF patients,established an ACLF mouse model with carbon tetrachloride(CCl 4),lipopolysaccharide(LPS),and D-galactose(D-gal),and constructed an in vitro hypoxia and hyperammonemia-triggered hepatocyte injury ***1 overexpression and knockdown adenovirus were used to assess the protective effect of LONP1 on liver injury and gluconeogenesis *** histopathology,biochemical index,mitochondrial morphology,cell viability and apoptosis,and the expression and activity of key gluconeogenic enzymes were detected to explore the underlying protective mechanisms of LONP1 in ***:We found that LONP1 and the expressions of gluconeogenic enzymes were downregulated in clinical ACLF liver ***,LONP1 overexpression remarkably attenuated liver injury,which was characterized by improved liver histopathological lesions and decreased serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in ACLF ***,mitochondrial morphology was improved upon overexpression of ***,the expression and activity of the key gluconeogenic enzymes were restored by LONP1 ***,the hepatoprotective effect was also observed in the hepatocyte injury model,as evidenced by improved cell viability,reduced cell apoptosis,and improved gluconeogenesis level and activity,while LONP1 knockdown worsened liver injury and gluconeogenesis ***

关键词： Acute-on-chronic liver failure Lon protease-1 Gluconeogenesis disturbance Mitochondrial dysfunction Metabolism

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Metabolic dysfunction-associated steatotic liver disease heterogeneity: Need of subtyping

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World Journal of Gastrointestinal Pathophysiology 2024年第2期15卷 1-14页

作者： Shahid Habib department of hepatology Liver Institute PLLCTucsonAZ 85716United States

Metabolic dysfunction-associated steatotic liver disease(MASLD)is a widespread global disease with significant health *** lifestyle,obesity,diabetes mellitus(DM),insulin resistance,and genetics have been implicated in the pathogenesis of MASLD.A significant degree of heterogeneity exists among each of above-mentioned risk *** of these risk factors translates into the heterogeneity of *** the other hand,MASLD can itself lead to insulin resistance and *** heterogeneity makes it difficult to assess the natural course of an individual with MASLD in clinical *** present MASLD is considered as one disease despite the variability of etiopathogenic processes,and we lack the consensus definitions of unique subtypes of *** this review,pathogenic processes of MASLD are discussed and a need of subtyping is recommended.

关键词： Metabolic dysfunctions-associated steatotic liver disease Visceral obesity Genetics Diabetes Insulin resistance

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Team players in the pathogenesis of metabolic dysfunctionsassociated steatotic liver disease:The basis of development of pharmacotherapy

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World Journal of Gastrointestinal Pathophysiology 2024年第4期15卷 1-29页

作者： Shahid Habib department of hepatology Liver Institute PLLCTucsonAZ 85712United States

Nutrient metabolism is regulated by several *** determinants of health with or without genetics are the primary regulator of metabolism,and an unhealthy lifestyle affects all modulators and mediators,leading to the adaptation and finally to the exhaustion of cellular *** steatosis is defined by presence of fat in more than 5%of *** hepatocytes,fat is stored as triglycerides in lipid *** steatosis results from a combination of multiple intracellular *** a healthy individual nutrient metabolism is regulated at several *** ranges from the selection of nutrients in a grocery store to the last step of consumption of ATP as an energy or as a building block of a cell as structural *** hormones,peptides,and genes have been described that participate in nutrient *** enzymes participate in each nutrient metabolism as described above from ingestion to generation of *** of now several publications have revealed very intricate regulation of nutrient metabolism,where most of the regulatory factors are tied to each other bidirectionally,making it difficult to comprehend chronological sequence of *** hormone is the primary regulator of all nutrients’metabolism both in prandial and fasting *** exerts its effects directly and indirectly on enzymes involved in the three main cellular function processes;metabolic,inflammation and repair,and cell growth and *** regulators that control the enzymatic functions through stimulation or suppression of a cell are nuclear receptors in especially farnesoid X receptor and peroxisome proliferator-activated receptor/RXR ligands,adiponectin,leptin,and *** hormone has direct effect on these final *** blood glucose level,serum lipids,incretin hormones,bile acids in conjunction with microbiota are intermediary modulators which are controlled by *** purpose of this review is to overvi

关键词： Metabolic dysfunctions-associated steatotic liver disease Visceral adiposity Obesity Farnesoid X receptor Peroxisome proliferator-activated receptor Insulin Adiponectin Glucagon-like peptide-1 Genetics PNPLA3 TM6SF2 Diabetes Dyslipidemia Pathogenesis

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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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Impact of metabolic dysfunction-associated steatotic liver disease on the efficacy of immunotherapy in patients with chronic hepatitis B-related hepatocellular carcinoma

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Cancer Biology & Medicine 2024年第9期21卷 813-825页

作者： Jiaxin Han Wentao Kuai Liu Yang Xuemei Tao Yuekui Wang Minghui Zeng Yuqin Li Yuqiang Mi Ningning Zhang Wei Lu Liang Xu Clinical School of the Tianjin Second People's Hospital Tianjin Medical University department of hepatology Tianjin Second People's Hospital Tianjin Institute of hepatology department of Hepatobiliary Oncology Liver Cancer Center Tianjin Medical University Cancer Institute & Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and TherapyTianjin Tianjin's Clinical Research Center for Cancer

Objective: To investigate the impact of metabolic dysfunction-associated steatotic liver disease(MASLD) on the efficacy of immune checkpoint inhibitor(ICI)-based therapy in patients with chronic hepatitis B(CHB)-related hepatocellular carcinoma(HCC).Methods: A total of 155 patients with CHB-related HCC who received ICI±based therapy(in the department of hepatology, Tianjin Second People's Hospital and department of Hepatobiliary Oncology, Tianjin Medical University Cancer Institute & Hospital) between April 2021 and December 2023 were *** were divided into two groups: MASLD concurrent with CHB [MASLD-CHB](n = 38), and CHB(n = 117).Results: The median progression-free survival(PFS, 6.9 months vs.9.3 months; P = 0.001), progressive disease(57.89% vs.37.61%; P = 0.028), and disease control rate(42.11% vs.62.39%; P = 0.028) in the MASLD-CHB group were significantly worse than the CHB *** median overall survival was not *** percentage of CD4+PD1+(17.56% vs.8.89%; P < 0.001) and CD8+PD1+ T cells(10.50% vs.7.42%; P = 0.005) in patient samples from the MASLD-CHB group were significantly higher than the CHB *** MASLD [hazard ratio(HR) = 1.921; 95% CI, 1.138±3.245; P = 0.015] and alpha-fetoprotein levels after 3 months of treatment(HR = 2.412; 95% CI, 1.360±4.279; P = 0.003) were independent risk factors for PFS in all ***: ICI-based therapy in patients with CHB-related HCC and concurrent MASLD resulted in poorer efficacy and shorter PFS compared to patients with CHB-related HCC alone.

关键词： Metabolic dysfunction-associated steatotic liver disease chronic hepatitis B efficacy hepatocellular carcinoma immunotherapy

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