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A literature review of genetics and epigenetics of HCV-related hepatocellular carcinoma: translational impact

Hepatobiliary Surgery and Nutrition 2024年第4期13卷 650-661页

作者： Ziyan Pan Wai-Kay Seto Chun-Jen Liu Yilei Mao saleh A.alqahtani Mohammed Eslam Storr Liver Centre Westmead Institute for Medical ResearchWestmead Hospital and University of SydneySydneyNSWAustralia Department of Medicine The University of Hong KongHong KongChina State Key Laboratory of Liver Research The University of Hong KongHong KongChina Department of Internal Medicine National Taiwan University HospitalTaipei Hepatitis Research Center National Taiwan University HospitalTaipei Graduate Institute of Clinical Medicine National Taiwan University College of MedicineTaipei Department of Liver Surgery Peking Union Medical College(PUMC)HospitalPUMC&Chinese Academy of Medical SciencesBeijingChina Organ Transplant Center of Excellence King Faisal Specialist Hospital&Research CenterRiyadhSaudi Arabia Division of Gastroenterology&Hepatology Johns Hopkins UniversityBaltimoreMDUSA

Background and Objective:Hepatocellular carcinoma(HCC)poses a significant global health burden and ranks as the fifth most prevalent cancer on a global *** C virus(HCV)infection remains one of the major risk factors for HCC *** is a heterogeneous disease,and the development of HCC caused by HCV is intricate and involves various factors,including genetic susceptibility,viral factors,immune response due to chronic inflammation,alcohol abuse,and metabolic dysfunction associated with fatty liver *** this review,we provide a comprehensive and updated review of research on the genetics and epigenetic mechanisms implicated in developing HCC associated with HCV *** also discuss the potential translational implications,including novel biomarkers and drugs for ***:A comprehensive literature search was conducted in June 2023 in PubMed and Embase *** Content and Findings:Recent findings indicate that a variety of genetic and epigenetic processes are involved in the pathogenesis and continue to exist even after the complete elimination of *** deregulation of the epigenome has been identified as a significant factor in the deletrious effects of liver disease,especially during the initial stages when genetic alterations are *** enduring“epigenetic memory”of gene expression is believed to be regulated by epigenetic mechanisms,indicating that alterations caused by HCV infection continue to exist and are linked to the risk of development of liver cancer even after successful *** biology analytical methods will be required to delineate the magnitude and significance of both genetic and epigenomic alterations in tumor ***:By facilitating a more profound understanding of these aspects,this will ultimately foster the advancement of novel therapies and ultimately improve outcomes for patients.

关键词： Epigenetics genetics hepatitis C virus-related hepatocellular carcinoma(HCV-related HCC) translational implications

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Current status of first-line therapy,anti-angiogenic therapy and its combinations of other agents for unresectable hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2021年第12期13卷 2038-2049页

作者： saleh a alqahtani Massimo G Colombo Division of Gastroenterology and Hepatology Johns Hopkins UniversityBaltimoreMD 21287United States Liver Transplant Center and BiostatisticsEpidemiologyand Scientific Computing DepartmentKing Faisal Specialist Hospital&Research CenterRiyadh 11564Saudi Arabia Liver Center IRCCS San Raffaele HospitalMilan 20132Italy

Globally,hepatocellular carcinoma(HCC)is a frequently diagnosed malignancy with rapidly increasing incidence and mortality ***,many of these patients are diagnosed in the advanced stages when locoregional treatments are not *** 2008,no effective drug treatments existed to prolong survival,until the breakthrough multi-tyrosine kinase inhibitor(TKI)sorafenib was *** remained the standard treatment option for advanced HCC for 10 years,with a battery of other candidate drugs in clinical trials failing to produce similar efficacy *** 2018,the REFLECT trial introduced another multi-TKI,lenvatinib,which has non-inferior overall survival compared with ***,offering patients and their treating physicians two effective treatment ***,immunotherapy-based drugs,such as atezolizumab and bevacizumab,have shown promising results in patients with unresectable *** review summarizes clinical trial and real-world data studies of sorafenib and lenvatinib in patients with unresectable *** offer guidance on the optimal choice between the two treatments and discuss the potential of immunotherapy-based combination;when more data become available,this will likely make the choice between sorafenib and lenvatinib somewhat obsolete.

关键词： Hepatocellular carcinoma Immune checkpoint inhibitor Lenvatinib Multityrosine kinase inhibitor Sorafenib

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Viral hepatitis as a risk factor for the development of hepatocellular carcinoma

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Hepatoma Research 2020年第9期6卷 21-38页

作者： saleh A.alqahtani Massimo Colombo Liver Transplantation Unit King Faisal Specialist Hospital&Research CentreRiyadh 12713Saudi Arabia Division of Gastroenterology and Hepatology John Hopkins UniversityBaltimoreMD 21287USA Center of Translational Research in Hepatology Humanitas HospitalRozzano 20089Italy.

Hepatocellular carcinoma(HCC)is the fourth leading global cause of tumor-related *** has a high prevalence in patients with chronic liver diseases,and it mostly results from cirrhosis caused by infection with blood-borne *** the implementation of various diagnostic and prevention strategies,the rates of new HCC cases and mortality are increasing globally due to the aging and growth of the world population as well as their increased exposure to dominant risk factors like alcohol,hepatitis B and C,and clinical correlates of metabolic *** studies indicate that sanitation practices,implementation of vaccination programs against hepatitis B,and expanded recognition and treatment of patients with chronic hepatitis B and C could greatly contribute to the eradication of viral hepatitis B and *** the availability of generic antiviral drugs could partially overcome the bottleneck represented by the lack of resources in low and middle-income countries,where viral hepatitis is the leading cause of liver cancer,the enthusiasm for the prevention of liver cancer through antiviral therapy is mitigated by the risk of cancer in many patients who are treated late in the hepatitis *** present work aimed to review in detail the various types,epidemiology,and carcinogenesis mechanisms of viral infections that are associated with a significantly increased risk for the development of HCC.

关键词： Antiviral agents hepatitis viruses hepatocellular carcinoma blood-borne hepatitis cirrhosis hepatitis B vaccine

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Systemic therapy for advanced cholangiocarcinoma:new options on the horizon

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Hepatoma Research 2020年第10期6卷 45-59页

作者： saleh A.alqahtani Massimo Colombo Liver Transplant Center King Faisal Specialist Hospital&Research CenterRiyadh 12713Saudi Arabia Division of Gastroenterology and Hepatology Johns Hopkins UniversityBaltimoreMD 21287USA Liver Center San Raffaele HospitalMilan 20132Italy

Patients with unresectable cholangiocarcinoma(CCA)face a poor prognosis,and there are few effective treatment options for the *** standard of care for patients with locally advanced or metastatic CCA is chemotherapy with a gemcitabine-based ***,the clinical benefit obtained with these regimens is modest,with a median overall survival of about one *** CCA that is chemotherapy-refractory or recurs after first-line chemotherapy,the treatment options are even more limited,and no relevant randomized controlled data are *** recent years,molecular profiling has shed light on the molecular basis of CCA and identified subgroups of patients that might benefit from a personalized treatment *** efforts resulted in the recent FDA approval of the fibroblast growth factor receptor(FGFR)inhibitor,pemigatinib,as a second-line treatment for patients with advanced CCA harboring an FGFR2-fusion or *** other targeted agents also are under evaluation in patients with CCA,of which the isocitrate dehydrogenase inhibitor has had the most promising ***,immunotherapy is being explored as a new treatment approach for advanced CCA patients;indeed,the immune checkpoint inhibitor pembrolizumab can already be used to treat CCAs that are mismatch repair *** review is a comprehensive overview of the treatment options for CCA and offers a glimpse into what the future could hold for these patients.

关键词： Cholangiocarcinoma fibroblast growth factor receptor inhibitor isocitrate dehydrogenase inhibitor immune checkpoint inhibitor

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COVID-19: An overview and a clinical update

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World Journal of Clinical Cases 2021年第1期9卷 8-23页

作者： Arunkumar Krishnan James P Hamilton saleh a alqahtani Tinsay A Woreta Division of Gastroenterology and Hepatology Johns Hopkins School of MedicineBaltimoreMD 21287United States Liver Transplant Center King Faisal Specialist Hospital&Research CenterRiyadh 12713Saudi Arabia

The outbreak of coronavirus disease-2019(COVID-19,previously known as 2019 nCoV)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in Wuhan City,China,has spread rapidly around the *** patients from the first cluster had an epidemiological connection to the Wuhan's Huanan Seafood Wholesale *** evidence has shown that SARSCoV-2 can be easily transmitted from person to person through close contact and respiratory droplets,posing a substantial challenge to public *** present,the research on SARS-CoV-2 is still in the primary ***,dexamethasone and remdesivir are appeared to be promising medical ***,there is no definite specific treatment,and the mainstay of treatment is still focused on supportive ***,over 150 vaccines are under *** is necessary to understand the nature of the virus and its clinical characteristics in order to find effectively manage the *** knowledge about this virus is rapidly evolving,and clinicians must update themselves *** present review comprehensively summarizes the epidemiology,pathogenesis,clinical characteristics,and management of COVID-19 based on the current evidence.

关键词： Coronaviruses COVID-19 SARS-CoV-2 Epidemiology Symptoms Laboratory Imaging Treatment Vaccines Prevention

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Hemodynamics in the immediate post-transplantation period in alcoholic and viral cirrhosis

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World Journal of Gastroenterology 2010年第5期16卷 608-612页

作者： Waleed K Al-Hamoudi saleh alqahtani Puneeta Tandon Samuel S Lee Gastroenterology Unit(59) College of MedicineKing Saud UniversityPO Box 2925Riyadh 11461 Saudi Arabia Gastroenterology unit King Faisal Specialist Hospital&Research CenterJeddah 21499Saudi Arabia Alberta Liver Transplantation Program University of AlbertaEdmontonAlbertaT6G 2X8 Canada Liver Unit University of CalgaryCalgary AlbertaT2N 4N1Canada

AIM:To study the hemodynamics in the immediate post transplant period and compare patients with alcoholic vs viral cirrhosis. METHODS:Between 2000-2003,38 patients were transplanted for alcoholic cirrhosis and 28 for postviral *** rate(HR),central venous pressure(CVP), mean arterial pressure(MAP),pulmonary capillary wedge pressure(PCWP),cardiac index(CI),systemic vascular resistance index(SVRI),pulmonary artery pressure(PAP),and pulmonary vascular resistance index(PVRI)were measured immediately and 24 h post transplantation. RESULTS:Hyperdynamic circulation persisted at 24 hfollowing transplantation with an elevated CI of 5.4± 1.3 L/(min×m 2 )and 4.9±1.0 L/(min×m 2 )in the viral and alcoholic groups,respectively,and was associated with a decreased *** the first 24 h, there was a significant decrease in HR and increase in MAP;the extent of the change was similar in both *** CVP,PCWP,and SVRI increased,and CI decreased in the viral patients,but not the alcoholic *** showed a lower PVRI(119±52 dynes/(cm 5 ×m 2 )vs 166±110 dynes/(cm5×m2),P< 0.05)and PAP(20±7 mmHg vs 24±7 mmHg,P< 0.05)compared to the viral group at 24 h. CONCLUSION:Hyperdynamic circulation persists in the immediate post-transplant period with a faster improvement in the viral *** patients have a more pronounced pulmonary vasodilatation.

关键词： Hemodynamics Cirrhosis Alcohol Viral Allograft

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Active Learning Strategies for Textual Dataset-Automatic Labelling

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Computers, Materials & Continua 2023年第8期76卷 1409-1422页

作者： Sher Muhammad Daudpota Saif Hassan Yazeed Alkhurayyif Abdullah saleh alqahtani Muhammad Haris Aziz Department of Computer Science Sukkur IBA UniversitySukkur65200Pakistan Al Quwayiyah College of Sciences and Humanities Shaqra UniversityShaqra15526Saudi Arabia Self-Development Skills Department Common First Year DeanshipKing Saud UniversityRiyadh12373Saudi Arabia STC’s Artificial Intelligence Chair Department of Information SystemsCollege of Computer and Information SciencesKing Saud UniversityRiyadh11451Saudi Arabia College of Engineering&Technology University of SargodhaSargodha40100Pakistan

The Internet revolution has resulted in abundant data from various sources,including social media,traditional media,*** the availability of data is no longer an issue,data labelling for exploiting it in supervised machine learning is still an expensive process and involves tedious human *** overall purpose of this study is to propose a strategy to automatically label the unlabeled textual data with the support of active learning in combination with deep *** specifically,this study assesses the performance of different active learning strategies in automatic labelling of the textual dataset at sentence and document *** achieve this objective,different experiments have been performed on the publicly available *** first set of experiments,we randomly choose a subset of instances from training dataset and train a deep neural network to assess performance on test *** the second set of experiments,we replace the random selection with different active learning strategies to choose a subset of the training dataset to train the same model and reassess its performance on test *** experimental results suggest that different active learning strategies yield performance improvement of 7% on document level datasets and 3%on sentence level datasets for auto labelling.

关键词： Active learning automatic labelling textual datasets

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Awareness and knowledge about glaucoma among patients visiting the screening clinic in Jeddah Eye Hospital,Saudi Arabia

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International Journal of Ophthalmology(English edition) 2021年第6期14卷 887-895页

作者： saleh M.alqahtani Marwan A Bakarman Ahmed Almanjoumi Sami H.Alzahrani Ministry of Health Jeddah 23545Saudi Arabia Department of Family and Community Medicine Faculty of Medicine in RabighKing Abdul Aziz UniversityJeddah 21589Saudi Arabia Ophthalmology Department Faculty of MedicineKing Abdulaziz UniversityJeddah 22234Saudi Arabia Family Medicine Department Faculty of MedicineKing Abdulaziz UniversityJeddah 22431Saudi Arabia

AIM:To explore levels and determinants of awareness and knowledge about glaucoma among ***:This was a cross-sectional study that included adult patients from October to the end of December 2018.A semi-structured questionnaire was designed by the researchers to measure the levels of awareness and knowledge about 18 basic information about *** sheet was divided into 4 domains:types of glaucoma,risk factors,clinical features,and management.A knowledge score(KS,range=0-18)was calculated,with higher scores indicating higher ***:A total of 383 patients responded to the questionnaire,61.9%males,mean±SD age was 38.5±12.94 years old,and 61.6%had a university degree or *** them,6.3%and 23.2%reported personal and family history of glaucoma,*** most frequently reported source of information about glaucoma was another person with glaucoma(28.2%),followed by physicians(24.8%)and TV(19.6%).Knowledge by item ranged from 3.1%to 82.5%correctness rate,while KS showed mean=5.91 and median=5;and reliability testing of the knowledge scale showed Cronbach’s alpha=*** KS were found among respondents with higher educational level(P=0.036),diabetes history(P=0.025),and personal(P<0.001)and family(P<0.001)history of ***:This study reveals low awareness and knowledge levels about glaucoma among the attendees of a local eye care hospital,where several misconceptions about disease risk factors,clinical features,and management are identified.

关键词： awareness knowledge glaucoma Saudi Arabia

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Diabetes mellitus is not associated with worse short term outcome in patients older than 65 years old post-liver transplantation

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World Journal of Hepatology 2023年第2期15卷 274-281页

作者： Saad Alghamdi Shaden Alamro Dhari Alobaid Elwy Soliman Ali Albenmousa Khalid Ibrahim Bzeizi saleh Alabbad saleh a alqahtani Dieter Broering Waleed Al-Hamoudi Liver and Small Bowel Health Centre Department KFSHRCRiyadh 11211Saudi Arabia Department of Medicine KFSHRCRiyadh 11211Saudi Arabia Department of Internal Medicine Minia UniversityMinya 61519Egypt Division of Gastroenterology and Hepatology Johns Hopkins UniversityBaltimoreMD 21287United States Liver Disease Research Center Department of MedicineCollege of MedicineKing Saud UniversityRiyadh 11451Saudi Arabia

BACKGROUND Non-alcoholic fatty liver disease is a global health care challenge and a leading indication of liver transplantation(LT).Hence,more patients with diabetes mellitus(DM)are undergoing LT,especially,above the age of *** To evaluate the impact of DM on short-term outcomes post-LT in patients over the age of *** We collected data of patients who underwent LT from January 2001 until December 2019 using our electronic medical *** assessed the impact of DM on short-term outcomes,one-year,post-LT based on the following variables:Survival at one year;acute cellular rejection(ACR)rates;intensive care unit(ICU)and hospital length of stay;and *** Total of 148 patients who are 65 year or older underwent LT during the study *** mean age is 68.5±3.3 years and 67.6%were *** median Model for End-stage Liver Disease score at time of transplantation was 22(6-39),39%of patients had hepatocellular carcinoma and 77.7%underwent living donor *** one-year survival was similar between DM patients and others,91%.ACR occurred in 13.5%of patients(P=0.902).The median ICU stay is 4.5-day P=*** rates of ICU and 90-d readmission were similar(P=0.821)and(P=0.194),*** The short-term outcome of elderly diabetic patients undergoing LT is similar to *** presence of DM in elderly LT candidates should not discourage physicians from transplant consideration in this cohort of patients.

关键词： Acute cellular rejection Diabetes mellitus Elderly Graft survival Liver transplantation

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Hepatocellular Carcinoma and the Role of Liver Transplantation:A Review

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Journal of Clinical and Translational Hepatology 2021年第5期9卷 738-748页

作者： Haris Muhammad Aniqa Tehreem Peng-Sheng Ting Merve Gurakar Sean Young Li Cem Simsek saleh A.alqahtani Amy K.Kim Ruhail Kohli Ahmet Gurakar Department of Internal Medicine Greater Baltimore Medical CenterMDUSA Department of Internal Medicine Sinai HospitalBaltimoreMDUSA Division of Gastroenterology and Hepatology Johns Hopkins University School of MedicineBaltimoreMDUSA Department of Medicine Osler Residency ProgramJohns Hopkins University School of MedicineBaltimoreMDUSA Duke University DurhamNCUSA

Hepatocellular carcinoma(HCC)is one of the leading causes of cancer deaths worldwide and liver transplantation(LT)is the only potentially curative *** the years,Milan criteria has been used for patient *** is ongoing research in this field with introduction of new biomarkers for HCC that can help guide future ***,newer therapies for downstaging of the tumor are being implemented to prevent dropout from the transplant *** addition,combination therapies for better outcome are under ***,the concept of living-donor LT and possible use of hepatitis C virus-positive donors has been implemented as an attempt to expand the organ ***,there is a conflict of opinion between different centers regarding its efficacy and data is *** aim of this review article is to outline the various selection criteria for LT,discuss the outcomes of LT in HCC patients,and explore future directions of LT for ***,a comprehensive PubMed/MEDLINE review was *** expand our search,references of the retrieved articles were also screened for additional *** selecting the studies,the authors independently reviewed them to identify the relevant *** careful evaluation 120 studies relevant to out topic are cited in the *** tables and two figures are also *** conclusion LT for HCC has evolved over the *** the introduction of several expanded criteria beyond Milan,the introduction of bridging therapies,such as transcatheter arterial chemoembolization and radiofrequency ablation,and the approval of newer systemic therapies,it is evident that there will be more LT recipients in the *** is promising to see ongoing trials and the continuous evolution of *** studies are needed to guide the development of a pre-LT criteria that can ensure low HCC recurrence risk and is not overly stringent,clarify the role of LDLT,and determine the optimal bridgin

关键词： Hepatocellular carcinoma Liver transplantation Model for endstage liver disease Trans-arterial radioembolization Locoregional therapies

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