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The switch triggering the invasion process:Lipid metabolism in the metastasis of hepatocellular carcinoma

Chinese Medical Journal 2024年第11期137卷 1271-1284页

作者： Jiaqian Zhang Zhicheng Zhang Zhangfan Wu Yufei Wang Zerui Zhang Limin Xia Department of Gastroenterology Institute of Liver and Gastrointestinal DiseasesHubei Key Laboratory of Hepato-Pancreato-Biliary DiseasesTongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China State Key Laboratory of Holistic Integrative Management of gastrointestinal Cancers and National Clinical research Center for Digestive Diseases Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi’anShaanxi 710032China

In humans,the liver is a central metabolic organ with a complex and unique histological *** carcinoma(HCC),which is a highly aggressive disease with a poor prognosis,accounts for most cases of primary liver *** an emerging hallmark of cancers,metabolic reprogramming acts as a runaway mechanism that disrupts homeostasis of the affected organs,including the ***,rewiring of the liver metabolic microenvironment,including lipid metabolism,is driven by HCC cells,propelling the phenotypes of HCC cells,including dissemination,invasion,and even metastasis in *** resulting formation of this vicious loop facilitates various malignant behaviors of HCC ***,few articles have comprehensively summarized lipid reprogramming in HCC ***,we have reviewed the general situation of the liver microenvironment and the physiological lipid metabolism in the liver,and highlighted the effects of different aspects of lipid metabolism on HCC metastasis to explore the underlying *** addition,we have recapitulated promising therapeutic strategies targeting lipid metabolism and the effects of lipid metabolic reprogramming on the efficacy of HCC systematical therapy,aiming to offer new perspectives for targeted therapy.

关键词： Hepatocellular carcinoma Invasion Metastasis Lipid metabolism Tumor microenvironment

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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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Nab-paclitaxel plus capecitabine as first-line treatment for advanced biliary tract cancers:An open-label,non-randomized,phase II clinical trial

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World Journal of Gastroenterology 2024年第30期30卷 3564-3573页

作者： Ling-Xiao Xu Jia-Jia Yuan Ran Xue Jun Zhou Department of gastrointestinal Oncology Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing)Peking University Cancer Hospital and InstituteBeijing 100142China

BACKGROUND Biliary tract cancers(BTCs)are a heterogeneous group of tumors with high malignancy,poor prognosis,and limited treatment *** To explore the efficacy and safety of nab-paclitaxel plus capecitabine as first-line treatment for advanced and metastatic *** This open-label,non-randomized,double-center,phase II clinical trial recruited systemic therapy-naive patients with unresectable or metastatic BTCs between April 2019 and June 2022 at Beijing Cancer Hospital and the First Hospital of China Medical *** patients were administered nab-paclitaxel(150 mg/m2,day 1)and capecitabine(2000 mg/m2,twice daily,days 1-7)in 14-day cycles until experiencing intolerable toxicity or disease *** primary outcome was the objective response rate(ORR).The secondary outcomes included the disease control rate(DCR),overall survival(OS),progression-free survival(PFS),and *** A total of 44 patients successfully completed the trial,with a median age of 64.00 years(interquartile range,35.00-76.00),and 26(59.09%)were *** response assessment was impeded for one patient due to premature demise from tumor *** the remaining 43 patients undergoing at least one imaging assessment,the ORR was 23.26%[95%confidence interval(CI):11.80%-38.60%],and the DCR was 69.77%(95%CI:53.90%-82.80%).The median OS was 14.1 months(95%CI:8.3-19.9),and the median PFS was 4.4 months(95%CI:2.5-6.3).A total of 41 patients(93.18%)experienced at least one adverse event(AE),with 10 patients(22.73%)encountering grade≥3 AEs,and the most frequent AEs of any grade were alopecia(79.50%),leukopenia(54.55%),neutropenia(52.27%),and liver dysfunction(40.91%),and no treatment-related deaths were *** Nab-paclitaxel plus capecitabine may be an effective and safe first-line treatment strategy for patients with advanced or metastatic BTCs.

关键词： Nab-paclitaxel Capecitabine Biliary tract cancer Objective response rate Phase II clinical trial

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Clinicopathological significance and immunotherapeutic outcome of claudin 18.2 expression in advanced gastric cancer:A retrospective study

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Chinese Journal of Cancer research 2024年第1期36卷 78-89页

作者： Changsong Qi Xiaoyi Chong Ting Zhou Mingyang Ma Jifang Gong Miao Zhang Jian Li Jun Xiao Xiaohui Peng Zhen Liu Zonghai Li Lin Shen Xiaotian Zhang State Key Laboratory of Holistic Integrative Management of gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDepartment of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational research(Ministry of Education/Beijing) Department of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China CARsgen Therapeutics Co. LtdShanghai 200231China CARsgen Life Sciences Co. LtdShanghai 200131China

Objective: Immunotherapeutic outcomes and clinical characteristics of claudin 18 isoform 2 positive(CLDN18.2-positive) gastric cancer(GC) vary in different clinical studies, making it difficult to optimize antiCLDN18.2 therapy. We conducted a retrospective analysis to explore the association of CLDN18.2 expression with clinicopathological characteristics and immunotherapeutic outcomes in ***: A total of 536 advanced GC patients from 2019 to 2021 in the CT041-CG4006 and CT041-ST-01clinical trials were included in the analysis. CLDN18.2 expression on ≥40% of tumor cells(2+, 40%) and CLDN18.2 expression on ≥70% of tumor cells(2+, 70%) were considered the two levels of positively expressed GC. The clinicopathological characteristics and immunotherapy outcomes of GC patients were analyzed according to CLDN18.2 expression ***: CLDN18.2 was expressed in 57.6%(cut-off: 2+, 40%) and 48.9%(cut-off: 2+, 70%) of *** death-ligand 1(PD-L1) and CLDN18.2 were co-expressed in 19.8% [combined positive score(CPS)≥1, CLDN18.2(cut-off: 2+, 40%)] and 17.2% [CPS≥5, CLDN18.2(cut-off: 2+, 70%)] of ***18.2 expression positively correlated with younger age, female sex, non-gastroesophageal junction(nonGEJ), and diffuse phenotype(Pliver metastasis(P<0.001)was less common in CLDN18.2-positive GC. Overall survival and immunotherapy-related progression-free survival(ir PFS) were inferior in the CLDN18.2-positive ***: CLDN18.2-positive GC is associated with poor prognosis and worse immunotherapeutic outcomes. The combination of anti-CLDN18.2 therapy, anti-PD-L1/PD-1 therapy, and chemotherapy for GC requires further investigation.

关键词： Gastric cancer claudin18.2 CT041 PD-L1 immunotherapy

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Role of albumin-bilirubin score in non-malignant liver disease

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World Journal of Gastroenterology 2024年第9期30卷 999-1004页

作者： Shi-Xue Xu Fan Yang Nan Ge Jin-Tao Guo Si-Yu Sun Department of Gastroenterology Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic TechniquesShengjing Hospital of China Medical UniversityShenyang 110004Liaoning ProvinceChina

The albumin-bilirubin(ALBI)score,which was proposed to assess the prognosis of patients with hepatocellular carcinoma,has gradually been extended to other liver diseases in recent years,including primary biliary cholangitis,liver cirrhosis,hepatitis,liver transplantation,and liver *** ALBI score is often compared with classical scores such as the Child-Pugh and model for end-stage liver disease scores or other noninvasive prediction *** is widely employed because of its immunity to subjective evaluation indicators and ease of obtaining detection *** increasing number of studies have confirmed that it is highly accurate for assessing the prognosis of patients with chronic liver disease;additionally,it has demonstrated good predictive performance for outcomes beyond survival in patients with liver diseases,such as decompensation *** article presents a review of the application of ALBI scores in various non-malignant liver diseases.

关键词： Albumin-bilirubin score liver cirrhosis Primary biliary cholangitis Hepatitis liver transplantation liver injury

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Retrospective study of the incidence, risk factors, treatment outcomes of bacterial infections at uncommon sites in cirrhotic patients

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World Journal of Hepatology 2024年第3期16卷 418-427页

作者： Sophie Schneitler Christina Schneider Markus Casper Frank Lammert Marcin Krawczyk Sören L Becker Matthias Christian Reichert Institute of Medical Microbiology and Hygiene Saarland UniversityHomburg 66421Germany Department of Medicine II Saarland University Medical CenterHomburg 66421Germany Health Sciences Hannover Medical SchoolHannover 30625Germany Laboratory of Metabolic liver Diseases Department of GeneralTransplant and Liver SurgeryCentre for Preclinical ResearchMedical University of WarsawWarsaw 02-097Poland

BACKGROUND Bacterial infections(BI)negatively affect the natural course of *** most frequent BI are urinary tract infections(UTI),pneumonia,and spontaneousbacterial peritonitis(SBP).AIM To assess the relevance of bacterial infections beyond the commonly recognized types in patients with cirrhosis and to investigate their relationship with other clinical *** We retrospectively analyzed patients with cirrhosis and BI treated between 2015 and 2018 at our tertiary care *** were classified as typical and atypical,and clinical as well as laboratory parameters were compared between the two *** In a cohort of 488 patients with cirrhosis,we identified 225 typical BI(95 UTI,73 SBP,72 pulmonary infections)and 74 atypical BIs,predominantly cholangitis and soft tissue infections(21 each),followed by intra-abdominal BIs(n=9),cholecystitis(n=6),head/throat BIs(n=6),osteoarticular BIs(n=5),and endocarditis(n=3).We did not observe differences concerning age,sex,or etiology of cirrhosis in patients with typical vs atypical *** BIs were more common in patients with more advanced cirrhosis,as evidenced by Model of End Stage liver Disease(15.1±7.4 vs 12.9±5.1;P=0.005)and Child-Pugh scores(8.6±2.5 vs 8.0±2;P=0.05).CONCLUSION Atypical BIs in cirrhosis patients exhibit a distinct spectrum and are associated with more advanced stages of the ***,the work-up of cirrhosis patients with suspected BI requires detailed work-up to elucidate whether typical BI can be identified.

关键词： Bacterial infection Empirical antibiotic therapy End-stage liver disease Escherichia coli Multi-resistant pathogens

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Sarcopenia and metabolic dysfunction associated steatotic liver disease:Time to address both

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World Journal of Hepatology 2024年第6期16卷 871-877页

作者： Rochelle Wong Li-Yun Yuan Division of gastrointestinal and liver Diseases Keck School of Medicine of University of Southern CaliforniaLos AngelesCA 90033United States

Sarcopenia and metabolic dysfunction associated steatotic liver disease(MASLD)are closely ***,traditionally a disease of the older adult and chronic disease population,has been closely studied as one of the pathophysiologic conditions at play in the development of *** share similar risk factors of insulin resistance and physical *** similar pathophysiology along the liver-muscle axis,sarcopenia has been studied as a risk factor for MASLD,and vice *** research suggests a bidirectional *** the chronicity of MASLD as a chronic inflammatory liver disease,it can break down muscle mass and lead to sarcopenia,while sarcopenia promotes intramuscular lipid accumulation that releases cytokines that can aggravate inflammation in the ***,for the longest time,a lack of consensus definition for MASLD and sarcopenia made it difficult to study their relationship and outcomes.A recent nomenclature update to diagnosing MASLD has made it easier for researchers to identify cohorts for ***,no gold standard technique to measure muscle mass or consensus sarcopenia definition has been identified *** studies are needed to reach a consensus and reduce diagnostic *** similar pathophysiology and shared risk factors between the two diseases,future research may also identify potential therapeutic targets along the liver-muscle axis that would benefit both sarcopenia and MASLD in order to maximize their outcomes.

关键词： Sarcopenia Steatotic liver disease Metabolic dysfunction Insulin resistance liver-muscle axis

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Fine-needle aspiration technique under endoscopic ultrasound guidance:A technical approach for RNA profiling of pancreatic neoplasms

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World Journal of gastrointestinal Oncology 2024年第6期16卷 2663-2672页

作者： Sabina Sherafedinovna Seyfedinova Olga Aleksandrovna Freylikhman Polina Sergeevna Sokolnikova Konstantin Aleksandrovich Samochernykh Anna Aleksandrovna Kostareva Olga Viktorovna Kalinina Evgeniy Gennadievich Solonitsyn research Laboratory of Digestive Cancer Almazov Medical Research CentreSaint-Petersburg 197341Russia research Laboratory of Molecular and Cellular Modeling and Gene Therapy Almazov Medical Research CentreSaint-Petersburg 197341Russia Head of Russian Neurosurgical Institute Named after Prof.A.L.Polenova Russian Neurosurgical Institute Named after Prof.A.L.PolenovaSaint-Petersburg 191014Russia Head of Institute of Molecular Biology and Genetics Almazov National Medical Research CentreSaint-Petersburg 197341Russia research Laboratory of Autoimmune and Autoinflammatory Diseases Almazov National Medical Research CentreSaint-Petersburg 197341Russia

BACKGROUND Early diagnosis of pancreatic ductal adenocarcinoma(PDAC)has been a longstanding *** prognosis of patients with PDAC depends on the stage at *** is necessary to identify biomarkers for the detection and differentiation of pancreatic tumors and optimize PDAC sample preparation procedures for DNA and RNA *** molecular studies are done using paraffin-embedded blocks;however,the integrity of DNA and RNA is often compromised in this ***,RNA isolated from human pancreatic tissue samples is generally of low quality,in part,because of the high concentration of endogenous pancreatic RNAse activity *** To assess the potential of endoscopic ultrasound-guided fine-needle aspiration(EUS-FNA)to obtain specimens from pancreatic neoplasms for subsequent RNA molecular profiling,including next-generation sequencing(NGS).METHODS Thirty-four EUS-FNA samples were included in this study:PDAC(n=15),chronic pancreatitis(n=5),pancreatic cysts(n=14),mucinous cysts(mucinous cystic neoplasia/intraductal papillary mucinous neoplasia)n=7,serous cystic neoplasms n=5,and pseudocysts n=*** material consisted of cyst fluid and cyst wall samples obtained by through-the-needle biopsy(TTNB).Samples were stored at -80℃ until *** purity(A260/230,A260/280 ratios),concentration,and integrity(RIN)were ***-time polymerase chain reaction was conducted on all samples,and small RNA libraries were prepared from solid mass *** RNA was successfully extracted from 29/34(85%)EUS-FNA samples:100% pancreatic adenocarcinoma samples,100% chronic pancreatitis samples,70% pancreatic fluid cyst samples,and 50%TTNB *** relative expression of GAPDH and HPRT were obtained for all successfully extracted RNA samples(n=29)including lowquality RNA *** concentration and nonoptimal RIN values(no less than 3)of RNA extracted from EUS-FNA samples did not prevent NGS library *** suitability of cyst fluid samples

关键词： Endoscopic ultrasound-guided,fine-needle aspiration Pancreatic cancer Pancreatic cysts RNA extraction Through-the-needle biopsy Next-generation sequencing

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Calculus bovis in hepatocellular carcinoma:Tumor molecular basis,Wnt/β-catenin pathway role,and protective mechanism

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World Journal of Gastroenterology 2024年第35期30卷 3959-3964页

作者： Khaled Mohamed Mohamed Koriem Department of Medical Physiology Medical Research and Clinical Studies InstituteNational Research CentreGiza 12622Egypt

In this editorial,we comment on the recent article by Huang et *** editorial focuses specifically on the molecular mechanisms of hepatocellular carcinoma(HCC),mechanism of Wnt/β-catenin pathway in HCC,and protective mechanism of Calculus bovis(CB)in *** cancer is the fourth most common cause of cancer-related deaths *** most prevalent kind of primary liver cancer,HCC,is typically brought on by long-term viral infections(hepatitis B and C),non-alcoholic steatohepatitis,excessive alcohol consumption,and other conditions that can cause the liver to become chronically inflamed and *** is a wellknown traditional remedy in China and Japan and has been used extensively to treat a variety of diseases,such as high fever,convulsions,and *** in lipid metabolism,cholesterol metabolism,bile acid metabolism,alcohol metabolism,and xenobiotic detoxification lead to fatty liver disease and liver ***,which is a tricarboxylic acid cycle intermediate,is vital to energy production and mitochondrial *** is also thought to be a signaling molecule in metabolism and in the development and spread of liver *** Wnt/β-catenin pathway is made up of a group of proteins that are essential for both adult tissue homeostasis and embryonic *** is frequently caused by the dysregulation of the Wnt/β-catenin signaling *** HCC liver carcinogenesis,Wnt/β-catenin signaling is activated by the expression of downstream target *** between the liver and the gut exists via the portal vein,biliary tract,and systemic ***"gutliver axis"controls intestinal *** of the main factors contributing to the development,progression,and treatment resistance of HCC is the abnormal activation of the Wnt/β-Catenin signaling ***,understanding this pathway is essential to treating *** ingredients of CB,particularly oleanolic acid,ergosterol,and ursolic acid,have anti-p

关键词： Hepatocellular carcinoma MicroRNAs Wnt/β-catenin pathway Calculus bovis Apoptosis

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Hepatitis B virus genotypes in precision medicine of hepatitis Brelated hepatocellular carcinoma:Where we are now

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World Journal of gastrointestinal Oncology 2024年第4期16卷 1097-1103页

作者： Caecilia H C Sukowati Sri Jayanti Turyadi Turyadi David H Muljono Claudio Tiribelli Eijkman research Center for Molecular Biology Research Organization for HealthNational Research and Innovation Agency of IndonesiaJakarta 10340Indonesia liver Cancer Unit Fondazione Italiana Fegato ONLUSTrieste 34149Italy Faculty of Medicine Hasanuddin UniversityMakassar 90245South SulawesiIndonesia Faculty of Medicine and Health University of SydneySydney 2050Australia

Hepatitis B virus(HBV)infection is a major player in chronic hepatitis B that may lead to the development of hepatocellular carcinoma(HCC).HBV genetics are diverse where it is classified into at least 9 genotypes(A to I)and 1 putative genotype(J),each with specific geographical distribution and possible different clinical outcomes in the *** diversity may be associated with the precision medicine for HBV-related HCC and the success of therapeutical approaches against HCC,related to different pathogenicity of the virus and host *** Editorial discusses recent updates on whether the classification of HBV genetic diversity is still valid in terms of viral oncogenicity to the HCC and its precision medicine,in addition to the recent advances in cellular and molecular biology technologies.

关键词： Hepatitis B virus Hepatocellular carcinoma Genotypes Pathogenesis Precision medicine

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