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Impact of microplastics and nanoplastics on liver health:Current understanding and future research directions

World Journal of Gastroenterology 2024年第9期30卷 1011-1017页

作者： Chun-Cheng Chiang hsuan yeh Ruei-Feng Shiu Wei-Chun Chin Tzung-Hai Yen School of Medicine University of PittsburghPittsburghPA 15213United States Pittsburgh Liver Research Center University of PittsburghPittsburghPA 15213United States Division of Experimental Pathology Department of PathologyUniversity of PittsburghPittsburghPA 15213United States Division of Endocrinology Department of PediatricsUniversity of PittsburghPittsburghPA 15213United States Center of Excellence for The Oceans National Taiwan Ocean UniversityKeelung 20224Taiwan Institute of Marine Environment and Ecology National Taiwan Ocean UniversityKeelung 20224TaiwanChina Department of Materials Science and Engineering University of California MercedMercedCA 95343United States Department of Nephrology Clinical Poison CenterChang Gung Memorial HospitalTaoyuan 333TaiwanChina College of Medicine Chang Gung UniversityTaoyuan 333TaiwanChina

With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn public attention only in the recent decade.This article summarizes recent works dedicated to understanding the impact of MPs/NPs on the liver-the largest digestive organ,which is one of the primary routes that MPs/NPs enter human bodies.The interrelated mechanisms including oxidative stress,hepatocyte energy re-distribution,cell death and autophagy,as well as immune responses and inflammation,were also featured.In addition,the disturbance of microbiome and gut-liver axis,and the association with clinical diseases such as metabolic dysfunction-associated fatty liver disease,steatohepatitis,liver fibrosis,and cirrhosis were briefly discussed.Finally,we discussed potential directions in regard to this trending topic,highlighted current challenges in research,and proposed possible solutions.

关键词： Microplastics Nanoplastics Liver Reactive oxidative species Cell death Autophagy Innate immunity Metabolic dysfunction-associated fatty liver disease Gut-liver axis

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Transcriptome analysis creates a new era of precision medicine for managing recurrent hepatocellular carcinoma

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World Journal of Gastroenterology 2023年第5期29卷 780-799页

作者： Chun-Cheng Chiang hsuan yeh Siew-Na Lim Wey-Ran Lin UPMC Hillman Cancer Center University of PittsburghPittsburghPA 15232United States School of Medicine University of PittsburghPittsburghPA 15213United States Department of Neurology Linkou Chang Gung Memorial HospitalTaoyuan 333Taiwan College of Medicine Chang Gung UniversityTaoyuan 333Taiwan

The high incidence of hepatocellular carcinoma(HCC)recurrence negatively impacts outcomes of patients treated with curative intent despite advances in surgical techniques and other locoregional liver-targeting therapies.Over the past few decades,the emergence of transcriptome analysis tools,including real-time quantitative reverse transcription PCR,microarrays,and RNA sequencing,has not only largely contributed to our knowledge about the pathogenesis of recurrent HCC but also led to the development of outcome prediction models based on differentially expressed gene signatures.In recent years,the single-cell RNA sequencing technique has revolutionized our ability to study the complicated crosstalk between cancer cells and the immune environment,which may benefit further investigations on the role of different immune cells in HCC recurrence and the identification of potential therapeutic targets.In the present article,we summarized the major findings yielded with these transcriptome methods within the framework of a causal model consisting of three domains:primary cancer cells;carcinogenic stimuli;and tumor microenvironment.We provided a comprehensive review of the insights that transcriptome analyses have provided into diagnostics,surveillance,and treatment of HCC recurrence.

关键词： Recurrent hepatocellular carcinoma Microarrays RNA sequencing Singlecell RNA sequencing Precision medicine Tumor heterogeneity Tumor microenvironment

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Hepatocellular carcinoma in patients with renal dysfunction: Pathophysiology, prognosis, and treatment challenges

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World Journal of Gastroenterology 2021年第26期27卷 4104-4142页

作者： hsuan yeh Chung-Cheng Chiang Tzung-Hai Yen Department of Nephrology Chang Gung Memorial Hospital and Chang Gung UniversityTaipei 105Taiwan Department of Gastroenterology and Hepatology Chang Gung Memorial HospitalTaoyuan 333Taiwan

The population of patients with hepatocellular carcinoma(HCC)overlaps to a high degree with those for chronic kidney disease(CKD)and end-stage renal disease(ESRD).The degrees of renal dysfunction vary,from the various stages of CKD to dialysis-dependent ESRD,which often affects the prognosis and treatment choice of patients with HCC.In addition,renal dysfunction makes treatment more difficult and may negatively affect treatment outcomes.This study summarized the possible causes of the high comorbidity of HCC and renal dysfunction.The possible mechanisms of CKD causing HCC involve uremia itself,long-term dialysis status,immunosuppressive agents for postrenal transplant status,and miscellaneous factors such as hormone alterations and dysbiosis.The possible mechanisms of HCC affecting renal function include direct tumor invasion and hepatorenal syndrome.Finally,we categorized the risk factors that could lead to both HCC and CKD into four categories:Environmental toxins,viral hepatitis,metabolic syndrome,and vasoactive factors.Both CKD and ESRD have been reported to negatively affect HCC prognosis,but more research is warranted to confirm this.Furthermore,ESRD status itself ought not to prevent patients receiving aggressive treatments.This study then adopted the well-known Barcelona Clinic Liver Cancer guidelines as a framework to discuss the indicators for each stage of HCC treatment,treatment-related adverse renal effects,and concerns that are specific to patients with pre-existing renal dysfunction when undergoing aggressive treatments against CKD and ESRD.Such aggressive treatments include liver resection,simultaneous liver kidney transplantation,radiofrequency ablation,and transarterial chemoembolization.Finally,focusing on patients unable to receive active treatment,this study compiled information on the latest systemic pharmacological therapies,including targeted and immunotherapeutic drugs.Based on available clinical studies and Food and Drug Administration labels,this study details the drug indications,side

关键词： Hepatocellular carcinoma Chronic kidney disease End-stage renal disease Hemodialysis Cancer prognosis Cancer therapeutics

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Trustworthiness Evaluation for Permissioned Blockchain-Enabled Applications

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Computers, Materials & Continua 2022年第11期73卷 2731-2755页

作者： Shi-Cho Cha Chuang-Ming Shiung Wen-Wei Li Chun-Neng Peng Yi-hsuan Hung Kuo-Hui yeh Department of Information Management National Taiwan University of Science and TechnologyTaiwanChina Department of Information Management National Dong Hwa UniversityHualienTaiwanChina Department of Computer Science and Engineering National Sun Yat-Sen UniversityKaohsiungTaiwanChina

As permissioned blockchain becomes a common foundation of blockchain-based circumstances for current organizations,related stakeholders need a means to assess the trustworthiness of the applications involved within.It is extremely important to consider the potential impact brought by the Blockchain technology in terms of security and privacy.Therefore,this study proposes a rigorous security risk management framework for permissioned blockchain-enabled applications.The framework divides itself into different implementation domains,i.e.,organization security,application security,consensus mechanism security,node management and network security,host security and perimeter security,and simultaneously provides guidelines to control the security risks of permissioned blockchain applications with respect to these security domains.In addition,a case study,including a security testing and risk evaluation on each stack of a specific organization,is demonstrated as an implementation instruction of our proposed risk management framework.According to the best of our knowledge,this study is one of the pioneer researches that provide a means to evaluate the security risks of permissioned blockchain applications from a holistic point of view.If users can trust the applications that adopted this framework,this study can contribute to the adoption of permissioned blockchain-enabled technologies.Furthermore,application providers can use the framework to perform gap analysis on their existing systems and controls and understand the risks of their applications.

关键词： Permissioned blockchain blockchain security blockchain risk evaluation

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Community-centered Disease Severity Assessment of Metabolic Dysfunction-associated Fatty Liver Disease

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Journal of Clinical and Translational Hepatology 2023年第5期11卷 1061-1068页

作者： Jee-Fu Huang Pei-Chien Tsai Ming-Lun yeh Chung-Feng Huang Ching-I Huang Mei-hsuan Lee Po-Yau Hsu Chih-Wen Wang Yu-Ju Wei Po-Cheng Liang Yi-Hung Lin Meng-hsuan Hsieh Jeng-Fu Yang Ming-Yen Hsieh Tyng-Yuan Jang Ming-Jong Bair Zu-Yau Lin Chia-Yen Dai Ming-Lung Yu Wan-Long Chuang Hepatobiliary Division Department of Internal MedicineKaohsiung Medical University HospitalKaohsiung Medical UniversityKaohsiung Graduate Institute of Clinical Medicine Kaohsiung Medical UniversityKaohsiung Faculty of Internal Medicine College of MedicineKaohsiung Medical UniversityKaohsiung Center for Liquid Biopsy and Cohort Research Kaohsiung Medical UniversityKaohsiung Institute of Clinical Medicine National Yang Ming Chiao Tung UniversityTaipei Department of Preventive Medicine Kaohsiung Medical University HospitalKaohsiung Division of Gastroenterology Department of Internal MedicineTaitung Mackay Memorial HospitalTaitung Mackay Medical College New Taipei City School of Medicine and Doctoral Program of Clinical and Experimental Medicine College of MedicineNational Sun Yat-sen UniversityKaohsiung Center of Excellence for Metabolic Associated Fatty Liver Disease National Sun Yat-sen UniversityKaohsiung

Background and Aims:Disease severity across the different diagnostic categories of metabolic dysfunction-associated fatty liver disease(MAFLD)remains elusive.This study assessed the fibrosis stages and features of MAFLD between different items.We also aimed to investigate the associations between advanced fibrosis and risk factors.Methods:This multicenter cross-sectional study enrolled adults participating in liver disease screening in the community.Patients were stratified following MAFLD diagnostic criteria,to group A(395 patients)for type 2 diabetes,group B(1,818 patients)for body mass index(BMI)>23 kg/m^(2),and group C(44 patients)for BMI≤23kg/m^(2) with at least two metabolic factors.Advanced fibrosis was defined as a fibrosis-4 index>2.67.Results:Between 2009 and 2020,1,948 MAFLD patients were recruited,including 478 with concomitant liver diseases.Advanced fibrosis was observed in 125 patients.A significantly larger proportion of patients in group C(25.0%)than in group A(7.6%)and group B(5.8%)had advanced fibrosis (p<0.01).Logistic regression analysis found that hepatitis B virus(HBV)/hepatitis C virus(HCV)coinfection(odds ratio[OR]:12.14,95%confidence interval[CI]:4.04-36.52;p<0.01),HCV infection(OR:7.87,95%CI:4.78-12.97;p<0.01),group C(OR:6.00,95%CI:2.53-14.22;p<0.01),and TC/LDL-C(OR:1.21,95%CI:1.06-1.38;p<0.01)were significant predictors of advanced fibrosis.Conclusions:A higher proportion of lean MAFLD patients with metabolic abnormalities had advanced fibrosis.HCV infection was significantly associated with advanced fibrosis.

关键词： Metabolic dysfunction-associated fatty liver disease Fibrosis-4 index Advanced fibrosis Community screening Viral hepatitis

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Low-power laser irradiation inhibits arecoline-induced fibrosis:an in vitro study

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International Journal of Oral Science 2017年第1期9卷 38-42页

作者： Mei-Chun yeh Ker-Kong Chen Min-hsuan Chiang Chia-Hsin Chen Ping-Ho Chen Huey-Er Lee Yan-Hsiung Wang School of Dentistry College of Dental MedicineKaohsiung Medical UniversityKaohsiungTaiwan Department of Dentistry Kaohsiung Medical University HospitalKaohsiung Medical UniversityKaohsiungTaiwan Orthopaedic Research Center College of MedicineKaohsiung Medical UniversityKaohsiungTaiwan Department of Physical Medicine and Rehabilitation Kaohsiung Municipal Ta-Tung HospitalKaohsiung Medical UniversityKaohsiungTaiwan and Department of Physical Medicine and Rehabilitation Kaohsiung Medical University HospitalKaohsiung Medical UniversityKaohsiungTaiwan

Oral submucous fibrosis （OSF） is a potentially malignant disorder that is characterized by a progressive fibrosis in the oral submucosa. Arecoline, an alkaloid compound of the areca nut, is reported to be a major aetiological factor in the development of OSF. Low-power laser irradiation （LPLI） has been reported to be beneficial in fibrosis prevention in different damaged organs. The aim of this study was to investigate the potential therapeutic effects of LPLI on arecoline-induced fibrosis. Arecoline- stimulated human gingival fibroblasts （HGFs） were treated with or without LPLI. The expression levels of the fibrotic marker genes alpha-smooth muscle actin （a-SMA） and connective tissue growth factor （CTGF/CCN2） were analysed by quantitative real- time reverse transcription polymerase chain reaction （RT-PCR） and western blots. In addition, the transcriptional activity of CCN2 was further determined by a reporter assay. The results indicated that arecoline increased the messenger RNA and protein expression of CCN2 and a-SMA in HGF. Interestingly, both LPLI and forskolin, an adenylyl cyclase activator, reduced the expression of arecoline-mediated fibrotic marker genes and inhibited the transcriptional activity of CCN2. Moreover, pretreatment with SQ22536, an adenylyl cyclase inhibitor, blocked LPLI＇s inhibition of the expression of arecoline-mediated fibrotic marker genes. Our data suggest that LPLI may inhibit the expression of arecoline-mediated fibrotic marker genes via the cAMP signalling pathway.

关键词： adenylate cyclase alpha-smooth muscle actin connective tissue growth factor fibrosis low-power laser irradiation

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Machine learning to relate PM2.5 and PM10 concentrations to outpatient visits for upper respiratory tract infections in Taiwan:A nationwide analysis

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World Journal of Clinical Cases 2018年第8期6卷 200-206页

作者： Mei-Juan Chen Pei-hsuan Yang Mi-Tren Hsieh Chia-Hung yeh Chih-Hsiang Huang Chieh-Ming Yang Gen-Min Lin Department of Electrical Engineering National Dong Hwa University Department of Electrical Engineering National Taiwan Normal University Department of Electrical Engineering National Sun Yat-sen University Department of Medicine Hualien Armed Forces General Hospital Departments of Medicine Tri-Service General HospitalNational Defense Medical Center

AIM To examine the accuracy of machine learning to relate particulate matter(PM) 2.5 and PM10 concentrations to upper respiratory tract infections(URIs).METHODS Daily nationwide and regional outdoor PM2.5 and PM10 concentrations collected over 30 consecutive days obtained from the Taiwan Environment Protection Administration were the inputs for machine learning, using multilayer perceptron(MLP), to relate to the subsequent one-week outpatient visits for URIs. TheURI data were obtained from the Centers for Disease Control datasets in Taiwan between 2009 and 2016. The testing used the middle month dataset of each season(January, April, July and October), and the training used the other months' datasets. The weekly URI cases were classified by tertile as high, moderate, and low volumes.RESULTS Both PM concentrations and URI cases peak in winter and spring. In the nationwide data analysis, MLP machine learning can accurately relate the URI volumes of the elderly(89.05% and 88.32%, respectively) and the overall population(81.75% and 83.21%, respectively) with the PM2.5 and PM10 concentrations. In the regional data analyses, greater accuracy is found for PM2.5 than for PM10 for the elderly, particularly in the Central region(78.10% and 74.45%, respectively), whereas greater accuracy is found for PM10 than for PM2.5 for the overall population, particularly in the Northern region(73.19% and 63.04%, respectively).CONCLUSION Short-term PM2.5 and PM10 concentrations were accurately related to the subsequent occurrence of URIs by using machine learning. Our findings suggested that the effects of PM2.5 and PM10 on URI may differ by age, and the mechanism needs further evaluation.

关键词： Particulate matter 2.5 Particulate matter 10 Upper respiratory infections Machine learning Air pollution

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Outreach onsite treatment with a simplified pangenotypic directacting anti-viral regimen for hepatitis C virus micro-elimination in a prison

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World Journal of Gastroenterology 2022年第2期28卷 263-274页

作者： Chun-Ting Chen Ming-Ying Lu Meng-hsuan Hsieh Pei-Chien Tsai Tsai-Yuan Hsieh Ming-Lun yeh Ching-I Huang Yi-Shan Tsai Yu-Min Ko Ching-Chih Lin Kuan-Yu Chen Yu-Ju Wei Po-Yao Hsu Cheng-Ting Hsu Tyng-Yuan Jang Ta-Wei Liu Po-Cheng Liang Ming-Yen Hsieh Zu-Yau Lin Chung-Feng Huang Jee-Fu Huang Chia-Yen Dai Wan-Long Chuang Yu-Lueng Shih Ming-Lung Yu Division of Gastroenterology and Hepatology Department of Internal MedicineTri-Service General Hospital Penghu BranchNational Defense Medical CenterPenghu County 88041Taiwan Division of Gastroenterology and Hepatology Department of Internal MedicineTri-Service General HospitalNational Defense Medical CenterTaipei 11490Taiwan Division of Hepatobiliary Department of Internal Medicine and Hepatitis CenterKaohsiung Medical University HospitalKaohsiung 80708Taiwan School of Medicine and Hepatitis Research Center College of Medicineand Center for Liquid Biopsy and Cohort ResearchKaohsiung Medical UniversityKaohsiung 80708Taiwan National Pingtung University of Science and Technology Pingtung 912Taiwan

BACKGROUND Prisoners are at risk of hepatitis C virus(HCV)infection,especially among the people who inject drugs(PWID).We implemented an outreach strategy in combination with universal mass screening and immediate onsite treatment with a simplified pan-genotypic direct-acting antivirals(DAA)regimen,12 wk of sofosbuvir/velpatasvir,in a PWID-dominant prison in Taiwan.AIM To implement an outreach strategy in combination with universal mass screening and immediate onsite treatment with a simplified pan-genotypic DAA regimen in a PWID-dominant prison in Taiwan.METHODS HCV-viremic patients were recruited for onsite treatment program for HCV micro-elimination with a pangenotypic DAA regimen,12 wk of sofosbuvir/velpatasvir,from two cohorts in Penghu Prison,either identified by mass screen or in outpatient clinics,in September 2019.Another group of HCV-viremic patients identified sporadically in outpatient clinics before mass screening were enrolled as a control group.The primary endpoint was sustained virological response(SVR12,defined as undetectable HCV ribonucleic acid(RNA)12 wk after end-of-treatment).RESULTS A total of 212 HCV-viremic subjects were recruited for HCV micro-elimination campaign;91 patients treated with sofosbuvir/Ledipasvir or glecaprevir/pibrentasvir before mass screening were enrolled as a control.The HCV microelimination group had significantly lower proportion of diabetes,hypertension,hyperlipidemia,advanced fibrosis and chronic kidney diseases,but higher levels of HCV RNA.The SVR12 rate was comparable between the HCV microelimination and control groups,95.8%(203/212)vs 94.5%(86/91),respectively,in intent-to-treat analysis,and 100%(203/203)vs 98.9%(86/87),respectively,in perprotocol analysis.There was no virological failure,treatment discontinuation,and serious adverse event among sofosbuvir/velpatasvir-treated patients in the HCV micro-elimination group.CONCLUSION Outreach mass screening followed by immediate onsite treatment with a simplified pangenotypic DAA regimen,sofosbuvir/velpatasvir,provi

关键词： Direct-acting antivirals Sofosbuvir Velpatasvir People who inject drugs Universal screen

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Retrotracheal thymoma masquerading as esophageal submucosal tumor

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World Journal of Gastroenterology 2005年第20期11卷 3165-3166页

作者： Sheung-Fat Ko Yuan-Hsiung Tsai hsuan-Ying Huang Shu-Hang Ng Fu-Ming Fang yeh Tang Ming-Tse Sung Ming-Jang Hsieh Departments of Radiology Chang Gung University Chang Gung Memorial Hospital at Kaohsiung Kaohsiung Hsien Taiwan China Departments of Pathology Chang Gung University Chang Gung Memorial Hospital at KaohsiungKaohsiung Hsien Taiwan China Departments of Oncology Chang Gung University Chang Gung Memorial Hospital at Kaohsiung Kaohsiung Hsien Taiwan China Departments of Thoracic Surgery Chang Gung Memorial Hospital at Kaohsiung Kaohsiung Hsien Taiwan China

A 42-year-old man presented with a two-year history of progressive dysphagia and hoarseness. Esophagogram and endoscopy revealed submucosal mass effect on the upper esophagus. Computed tomography and magnetic resonance imaging revealed an elongated mass in the retrotracheal region of the lower neck with extension to the posterior mediastinum. Partial tumor resection and histopathological evaluation revealed a WHO type B2 thymoma. Adjuvant radiation and chemotherapy were subsequently administered resulting in complete tumor regression. To our knowledge, this is the first report of ectopic retrotracheal thymoma with clinical and imaging manifestations mimicking those for esophageal submucosal tumor.

关键词：胸腺肿瘤食道肿瘤肿瘤入侵病理机制

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Treatment efficacy for patients with chronic hepatitis C and preexisting hepatocellular carcinoma by directly acting antivirals

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Hepatoma Research 2020年第4期6卷 30-38页

作者： Chia-Yen Dai Chung-Feng Huang Meng-hsuan Hsieh Ching-I Huang Ming-Lun yeh Pei-ChienTsai Ching-Chih Lin Meng-Szu Lee Jeng-Fu Yang Po-Yao Hsu Yu-Ju Wei Cheng-Ting Hsu Po-Cheng Liang Yi-Hung Lin Jee-Fu Huang Wan-Long Chuang Ming-Lung Yu Hepatobiliary Division Department of Internal MedicineKaohsiung Medical University HospitalKaohsiung Medical UniversityKaohsiung 807Taiwan Health Management Center&Department of Community Medicine Kaohsiung Medical University HospitalKaohsiung Medical UniversityKaohsiung 807Taiwan Faculty of Internal Medicine College of MedicineKaohsiung Medical UniversityKaohsiung 807Taiwan Department of Biological Science and Technology College of Biological Science and TechnologyNational Chiao Tung UniversityHsin-ChuKaohsiung 807Taiwan

Aim:Despite the high cure rate of interferon-free directly acting antivirals(DAAs)for chronic hepatitis C(CHC)patients,the treatment efficacy for patients with preexisting hepatocellular carcinoma(HCC)remains undefined.We aimed in the present study to address the issue by using novel DAAs in treating CHC patients who were adherent to treatment in Taiwan.Methods:CHC patients with or without HCC were consecutively enrolled.The primary objective was sustained virological response(SVR)defined as undetectable HCV RNA throughout 12 weeks of a post-treatment follow-up period(SVR12).Only patients with available SVR12 were enrolled for final analysis.Results:A total of 1237 patients(1113 non-HCC,101 inactive HCC and 23 active HCC)were enrolled.The overall SVR12 rate was 98.9%,and was similar between HCV patients with and without pre-existing HCC(98.4%vs.98.9%,P=0.64).While HCC patients were classified as those who had active or inactive HCC,the SVR12 was also similar between patients with and without active HCC(95.7%vs.99.0%,P=0.34).Among the 101 patients without viable HCC at the time of DAA initiation,eighty-four patients exhibited curative therapy and the other 17 ;patients experienced HCC recurrence before DAAs.Among the 23 patients with viable HCC at the time of DAA treatment,10 patients had received curative therapy for HCC whereas the remaining 13 patients had HCC that was never cured.The SVR12 rates were also similar among the four subpopulations,being 98.8%(83/84),100%(17/17),90%(9/10)and 100%(13/13)respectively.Conclusion:CHC patients with HCC who were adherent to potent DAAs achieved similar SVR12 rate compared to those without HCC and could be effectively treated.

关键词： Directly acting antiviral chronic hepatitis C hepatitis C virus hepatocellular carcinoma sustained virological response

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