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

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

作者： Ziyan Pan wa.-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 wa. 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

Prevalence and risk factors for impaired renal function among Asian patients with nonalcoholic fatty liver disease

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 241-248页

作者： Chao Sun George Boon-Bee Goh wa.-Cheng Chow wa.-Kheong Chan Grace Lai-Hung Wong wa.-kay seto Yi-Hsiang Huang Han-Chieh Lin I-Cheng Lee Hye Won Lee Seung Up Kim Vincent wa.-Sun Wong Jian-Gao Fan Center for Fatty Liver Disease Department of GastroenterologyXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai Key Lab of Pediatric Gastroenterology and NutritionShanghai 200092China Department of Gastroenterology&Hepatology Singapore General HospitalSingaporeSingapore Gastroenterology and Hepatology Unit Department of MedicineFaculty of MedicineUniversity of MalayaKuala LumpurMalaysia Department of Medicine and Therapeutics and State Key Laboratory of Digestive Disease The Chinese University of Hong KongHong KongChina Department of Medicine The University of Hong KongHong KongChina Institute of Clinical Medicine National Yang Ming Chiao Tung University School of MedicineTaipeiTaiwanChina Division of Gastroenterology and Hepatology Taipei Veterans General HospitalTaipeiTaiwanChina Faculty of Medicine National Yang Ming Chiao Tung University School of MedicineTaipeiTaiwanChina Department of Internal Medicine Yonsei University College of MedicineSeoulKorea

Background:Nonalcoholic fatty liver disease(NAFLD)is associated with impaired renal function,and both diseases often occur alongside other metabolic ***,the prevalence and risk factors for impaired renal function in patients with NAFLD remain *** objective of this study wa. to identify the prevalence and risk factors for renal impairment in NAFLD ***:All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective *** fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase(FAST),Agile 3+and Agile 4 *** renal function and chronic kidney disease(CKD)were defined by an estimated glomerular filtration rate(eGFR)with value of<90 mL/min/1.73 m^(2) and<60 mL/min/1.73 m^(2),respectively,as estimated by the CKD-Epidemiology Collaboration(CKD-EPI)***:Among 529 included NAFLD patients,the prevalence rates of impaired renal function and CKD were 37.4%and 4.9%,*** multivariate analysis,a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+and Agile 4 scores were independent risk factors for CKD(P<0.05).Furthermore,increased fasting plasma glucose(FPG)and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome(P<0.05).Compared with patients with normoglycemia,those with prediabetes[FPG≥5.6 mmol/L or hemoglobin A1c(HbA1c)≥5.7%]were more likely to have impaired renal function(P<0.05).Conclusions:Agile 3+and Agile 4 are reliable for identifying NAFLD patients with high risk of *** glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.

关键词： Nonalcoholic fatty liver disease Impaired renal function Agile 3+ Agile 4 Metabolic syndrome

Effects of SARS-CoV-2 infection on incidence and treatment strategies of hepatocellular carcinoma in people with chronic liver disease

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World Journal of Hepatology 2024年第2期16卷 211-228页

作者： Lung-Yi Mak Matthew Shing Hin Chung Xue Li Francisco Tsz Tsun Lai Eric Yuk Fai wa. Celine Sze Ling Chui Franco Wing Tak Cheng Esther wa. Yin Chan Ching Lung Cheung Ivan Chi Ho Au Xi Xiong wa.-kay seto Man-Fung Yuen Carlos King Ho Wong Ian Chi Kei Wong Department of Medicine The University of Hong KongHong KongChina State Key Laboratory of Liver Research The University of Hong KongHong KongChina Department of Pharmacology and Pharmacy The University of Hong KongHong KongChina Laboratory of Data Discovery for Health(D24H) Hong Kong Science and Technology ParkHong KongChina Department of Family Medicine and Primary Care The University of Hong KongHong KongChina School of Nursing The University of Hong KongHong KongChina School of Public Health The University of Hong KongHong KongChina Research Department of Practice and Policy University College LondonLondon WC1E 6BTUnited Kingdom Aston School of Pharmacy Aston UniversityBirmingham B47ETUnited Kingdom

BACKGROUND Chronic liver disease(CLD)wa. associated with adverse clinical outcomes among people with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** To determine the effects of SARS-CoV-2 infection on the incidence and treatment strategy of hepatocellular carcinoma(HCC)among patients with *** A retrospective,territory-wide cohort of CLD patients wa. identified from an electronic health database in Hong *** with confirmed SARS-CoV-2 infection[coronavirus disease 2019(COVID-19)+CLD]between January 1,2020 and October 25,2022 were identified and matched 1:1 by propensity-score with those without(COVID-19-CLD).Each patient wa. followed up until death,outcome event,or November 15,*** outcome wa. incidence of *** outcomes included all-cause mortality,adverse hepatic outcomes,and different treatment strategies to HCC(curative,non-curative treatment,and palliative care).Analyses were further stratified by acute(within 20 d)and post-acute(21 d or beyond)phases of SARS-CoV-2 *** rate ratios(IRRs)were estimated by Poisson regression *** Of 193589 CLD patients(>95%non-cirrhotic)in the cohort,55163 patients with COVID-19+CLD and 55163 patients with COVID-19-CLD were included after 1:1 propensity-score *** 249-d median follow-up,COVID-19+CLD wa. not associated with increased risk of incident HCC(IRR:1.19,95%CI:0.99-1.42,P=0.06),but higher risks of receiving palliative care for HCC(IRR:1.60,95%CI:1.46-1.75,P<0.001),compared to *** both acute and post-acute phases of infection,COVID-19+CLD were associated with increased risks of allcause mortality(acute:IRR:7.06,95%CI:5.78-8.63,P<0.001;post-acute:IRR:1.24,95%CI:1.14-1.36,P<0.001)and adverse hepatic outcomes(acute:IRR:1.98,95%CI:1.79-2.18,P<0.001;post-acute:IRR:1.24,95%CI:1.13-1.35,P<0.001),compared to *** Although CLD patients with SARS-CoV-2 infection were not associated with increased risk of HCC,they

关键词： SARS-CoV-2 infection Chronic liver disease Long COVID Post-COVID-19 syndrome Cirrhosis Hepatocellular carcinoma

Chronic hepatitis B and metabolic risk factors:A call for rigorous longitudinal studies

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World Journal of Gastroenterology 2019年第3期25卷 282-286页

作者： wa.-kay seto Department of Medicine the University of Hong Kong Queen Mary Hospital Department of Medicine the University of Hong Kong-Shenzhen Hospital State Key Laboratory for Liver Research the University of Hong Kong

Long-term nucleos(t)ide analogue therapy in chronic hepatitis B virus(HBV)infection is effective in suppressing viral replication and reducing liver-related complications. However, HBV-related liver events can still occur in different patient sub-groups. There is emerging evidence that, similar to chronic hepatitis C virus infection, metabolic risk factors may play a role in the disease process of chronic HBV. While the mechanistic nature of metabolic-HBV interactions remains uncertain, studies in different HBV-infected populations have demonstrated that hepatic steatosis, increased body-mass index, diabetes, or a combination of different metabolic risk factors are associated with an increased risk of hepatocellular carcinoma and cirrhosis. The impact of metabolic risk factors is especially prominent in patients with quiescent virological activity,including on-treatment patients with effective viral suppression. As the proportion of on-treatment chronic HBV patients increases worldwide,longitudinal studies determining the relative risks of different metabolic parameters with respect to clinical outcomes are needed. Future studies should also determine if metabolic-directed interventions can improve disease outcomes in chronic HBV.

关键词： Hepatitis B virus Diabetes Obesity Steatosis Non-alcoholic fatty liver disease Body-mass index

Hepatitis B virus reactivation during immunosuppressive therapy: Appropriate risk stratification

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World Journal of Hepatology 2015年第6期7卷 825-830页

Our understanding of hepatitis B virus(HBV) reactivation during immunosuppresive therapy has increased remarkably during recent years. HBV reactivation in hepatitis B surface antigen(HBs Ag)-positive individuals has been well-described in certain immunosuppressive regimens, including therapies containing corticosteroids, anthracyclines, rituximab, antibody to tumor necrosisfactor(anti-TNF) and hematopoietic stem cell transplantation(HSCT). HBV reactivation could also occur in HBs Ag-negative, antibody to hepatitis B core antigen(anti-HBc) positive individuals during therapies containing rituximab, anti-TNF or *** HBs Ag-positive patients, prophylactic antiviral therapy is proven to the effective in preventing HBV reactivation. Recent evidence also demonstrated entecavir to be more effective than lamivudine in this aspect. For HBs Ag-negative, antiHBc positive individuals, the risk of reactivations differs with the type of immunosuppression. For rituximab, a prospective study demonstrated the 2-year cumulative risk of reactivation to be 41.5%, but prospective data is still lacking for other immunosupressive regimes. The optimal management in preventing HBV reactivation would involve appropriate risk stratification for different immunosuppressive regimes in both HBs Ag-positive and HBs Ag-negative, anti-HBc positive individuals.

关键词： Hepatitis B virus Antibody to hepatitis Bcore antigen Hepatitis B surface antigen Rituximab Antigen CD20 Hematopoietic stem cell transplantation Antibody to tumor necrosis factor Occult

Application of Big Data analysis in gastrointestinal research

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World Journal of Gastroenterology 2019年第24期25卷 2990-3008页

作者： Ka-Shing Cheung wa. K Leung wa.-kay seto Department of Medicine The University of Hong KongQueen Mary HospitalHong KongChina Department of Medicine The University of Hong Kong- Shenzhen HospitalShenzhen 518053Guangdong ProvinceChina

Big Data,which are characterized by certain unique traits like volume,velocity and value,have revolutionized the research of multiple fields including *** Data in health care are defined as large datasets that are collected routinely or automatically,and stored *** the rapidly expanding volume of health data collection,it is envisioned that the Big Data approach can improve not only individual health,but also the performance of health care *** application of Big Data analysis in the field of gastroenterology and hepatology research has also opened new research *** it retains most of the advantages and avoids some of the disadvantages of traditional observational studies(case-control and prospective cohort studies),it allows for phenomapping of disease heterogeneity,enhancement of drug safety,as well as development of precision medicine,prediction models and personalized *** randomized controlled trials,it reflects the real-world situation and studies patients who are often under-represented in randomized controlled ***,residual and/or unmeasured confounding remains a major concern,which requires meticulous study design and various statistical adjustment *** potential drawbacks include data validity,missing data,incomplete data capture due to the unavailability of diagnosis codes for certain clinical situations,and individual *** continuous technological advances,some of the current limitations with Big Data may be further *** review will illustrate the use of Big Data research on gastrointestinal and liver diseases using recently published examples.

关键词： Healthcare dataset Epidemiology Gastric cancer Inflammatory bowel disease Colorectal cancer Hepatocellular carcinoma Gastrointestinal bleeding

Growth arrest-specific gene 2 suppresses hepatocarcinogenesis by intervention of cell cycle and p53-dependent apoptosis

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World Journal of Gastroenterology 2019年第32期25卷 4715-4726页

作者： Ran-Xu Zhu Alfred Sze Lok Cheng Henry Lik Yuen Chan Dong-Ye Yang wa.-kay seto Department of Gastroenterology and Hepatology The University of Hong Kong–Shenzhen HospitalShenzhen 518053Guangdong ProvinceChina School of Biomedical Sciences The Chinese University of Hong KongHong KongChina Department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina

BACKGROUND Growth arrest-specific gene 2(GAS2)plays a role in modulating in reversible growth arrest cell cycle,apoptosis,and cell ***2 protein is universally expressed in most normal tissues,particularly in the liver,but is depleted in some tumor ***,the functional mechanisms of GAS2 in hepatocellular carcinoma(HCC)are not fully *** To investigate the function and mechanism of GAS2 in *** GAS2 expression in clinic liver and HCC specimens wa. analyzed by real-time PCR and western *** proliferation wa. analyzed by counting,MTS,and colony formation *** cycle analysis wa. performed by flow *** apoptosis wa. investigated by Annexin V apoptosis assay and western *** GAS2 protein expression wa. lower in HCC than in normal *** of GAS2 inhibited the proliferation of HCC cells with wide-type p53,while knockdown of GAS2 promoted the proliferation of hepatocytes(Pwa. dependent on p53,which wa. increased by etoposide *** expression of p53 and apoptosis markers wa. further enhanced when GAS2 wa. upregulated,but became diminished upon downregulation of *** the clinic specimen,GAS2 wa. downregulated in more than 60%of *** average fold changes of GAS2 expression in tumor tissues were significantly lower than those in paired non-tumor tissues(Pwa..

关键词： Growth arrest-specific gene 2 Cell cycle Apoptosis Hepatocellular carcinoma p53-dependent signaling pathwa.

Prediction of hepatocellular carcinoma development by aminotransferase to platelet ratio index in primary biliary cholangitis

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World Journal of Gastroenterology 2017年第44期23卷 7863-7874页

作者： Ka-Shing Cheung wa.-kay seto James Fung Lung-Yi Mak Ching-Lung Lai Man-Fung Yuen Department of Medicine The University of Hong Kong Queen Mary Hospital State Key Laboratory for Liver Research The University of Hong Kong

AIM To investigate the usefulness of aspartate aminotransferase to platelet ratio index(APRI) in predicting hepatocellular carcinoma(HCC) risk in primary biliary cholangitis(PBC).METHODS We identified PBC patients between 2000 and 2015 by searching the electronic medical database of a tertiary center. The hazard ratio(HR) of HCC with different risk factors wa. determined by Cox proportional hazards model. RESULTS One hundred and forty-four PBC patients were recru-ited. Patients were diagnosed at a median age of 57.8 years [interquartile range(IQR): 48.7-71.5 years), and 41(28.5%) patients had cirrhosis at baseline. The median follow-up duration wa. 6.9 years(range: 1.0-26.3 years). Twelve patients developed HCC, with an incidence rate of 10.6 cases per 1000 patient-years. The overall 5-, 10-and 15-year cumulative incidences of HCC were 2.3% 95%CI: 0%-4.8%), 8.4%(95%CI: 1.8%-14.5%) and 21.6%(6.8%-34.1%), respectively. Older age(HR = 1.07), cirrhosis(HR = 4.38) and APRI at 1 year after treatment(APRI-r1) > 0.54(HR = 3.94) were independent factors for HCC development. APRI-r1, when combined with treatment response, further stratified HCC risk(log rank P wa. 0.77(95%CI: 0.64-0.88).CONCLUSION APRI-r1 can be used to predict the development of HCC in PBC patients. Combination of APRI-r1 with treatment response can further stratify the HCC risk.

关键词： Aspartate aminotransferase Platelet ratio index Hepatocellular carcinoma Primary biliary cholangitis Ursodeoxycholic acid Cirrhosis

Epidemiology and natural history of Wilson's disease in the Chinese: A territory-based study in Hong Kong between 2000 and 2016

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World Journal of Gastroenterology 2017年第43期23卷 7716-7726页

作者： Ka-Shing Cheung wa.-kay seto James Fung Lung-Yi Mak Ching-Lung Lai Man-Fung Yuen Department of Medicine The University of Hong KongQueen Mary Hospital State Key Laboratory for Liver Research The University of Hong Kong

AIM To investigate the epidemiology and natural history of Wilson's disease in the *** Data were retrieved via electronic search of hospital medical registry of the Hong Kong Hospital Authority,which covers all the public healthcare services. We identified cases of Wilson's disease between 2000 and 2016 by the International Classification of Diseases(ICD)-9 code. We analyzed the incidence rate,prevalence and adverse outcomes of Wilson's *** We identified 211 patients(male cases 104; female cases 107; median age 27.2 years,IQR: 17.1-38.6 years; duration of follow-up 8.0 years,IQR: 5.0-14.0 years). The average annual incidence rate wa. 1.44 per million person-years while the prevalence wa. 17.93 per million. Between 2000 and 2016,there wa. a decrease in the annual incidence rate from 1.65 to 1.23 per million person-years(P = 0.010),whereas there wa. an increase in the annual prevalence from 7.80 to 25.20 per million(P wa. a significant increase in the prevalence of Wilson's disease in Hong Kong. The prognosis wa. favorable except for those with cirrhosis or concomitant viral hepatitis.

关键词： Hepaticolenticular degeneration Cirrhosis Hepatocellular carcinoma Transplantation