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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 wan Celine Sze Ling Chui Franco Wing Tak Cheng esther Wai yin Chan ching Lung Cheung Ivan Chi Ho Au Xi Xiong Wai-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)was associated with adverse clinical outcomes among people with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.AIM To determine the effects of SARS-CoV-2 infection on the incidence and treatment strategy of hepatocellular carcinoma(HCC)among patients with CLD.METHODS A retrospective,territory-wide cohort of CLD patients was identified from an electronic health database in Hong Kong.Patients 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 was followed up until death,outcome event,or November 15,2022.Primary outcome was incidence of HCC.Secondary 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 infection.Incidence rate ratios(IRRs)were estimated by Poisson regression models.RESULTS 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 matching.Upon 249-d median follow-up,COVID-19+CLD was 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 COVID-19-CLD.In 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 COVID-19-CLD.CONCLUSION Although CLD patients with SARS-CoV-2 infection were not associated with increased risk of HCC,they were more likely to receive palliative treatment

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

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Genomics-driven derivatization of the bioactive fungal sesterterpenoid variecolin:Creation of an unnatural analogue with improved anticancer properties

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Acta Pharmaceutica Sinica B 2024年第1期14卷 421-432页

作者： Dexiu Yan Jemma Arakelyan Teng wan Ritvik Raina Tsz Ki Chan Dohyun Ahn Vladimir Kushnarev Tsz Kiu Cheung Ho ching Chan Inseo Choi Pui yi Ho Feijun Hu Yujeong Kim Hill Lam Lau ying Lo Law Chi Seng Leung Chun yin Tong Kai Kap Wong Wing Lam yim Nikolay S.Karnaukhov Richard Y.C.Kong Maria V.Babak Yudai Matsuda Department of Chemistry City University of Hong KongHong Kong SARChina iGEM Team“VarieCure” City University of Hong KongHong Kong SARChina Department of Biomedical Engineering City University of Hong KongHong Kong SARChina Moscow Clinical Research Center Named After A.S.Loginov Moscow 111123Russian Federation

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin(1)and variecolactone(2)was identified in Aspergillus aculeatus ATCC 16872.Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB.Intriguingly,the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues(5-7).Analysis of the compounds’anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities,5 was associated with significantly reduced toxic side effects in cancer-bearing mice,indicating its potentially broader therapeutic window.Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

关键词： Animal studies Anticancer properties Biosynthesis Natural products Sesterterpenoids Synthetic biology Terpene synthases Variecolin

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The H2BG53D oncohistone directly upregulates ANXA3 transcription and enhances cell migration in pancreatic ductal adenocarcinoma

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1482-1485页

作者： yi ching esther wan Jiaxian Liu Lina Zhu Tze Zhen Evangeline Kang Xiaoxuan Zhu John Lis Toyotaka Ishibashi Charles G.Danko Xin wang Kui Ming Chan Department of Biomedical Sciences City University of Hong KongHong KongChina Key Laboratory of Biochip Technology Biotech and Health CentreShenzhen Research Institute of City University of Hong KongShenzhenChina Department of Molecular Biology and Genetics Cornell UniversityNew YorkNYUSA Division of Life Science Hong Kong University of Science and TechnologyHong KongChina USA James A Baker Institute for animal health Cornell UniversityNew YorkNYUSA

Dear Editor,Histones are essential proteins in compacting genomic DNA and regulating gene expression.Previous studies on histone H3 oncohistones in pediatric brain cancers1,2 and chondroblastoma3,documented the transcriptomic reprogramming through the alterations of histone modifications.We recently reported the identification of a novel cancer associated mutation,the H2BG53-to-D in pancreatic ductal adenocarcinoma(PDAC)4.We showed that the H2BG53D mutation weakens the interaction between nucleosomal DNA and histone octamer,subsequently enhances transcription in vitro.We further showed that cells expressing the G53D mutant H2B acquired oncogenic phenotypes in our CRISPRCas9 knock-in model.However,the mechanism by which H2BG53D mutation promotes PDAC remains unknown.

关键词： H2B expression adenocarcinoma

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Cancer-associated histone mutation H2BG53D disrupts DNA–histone octamer interaction and promotes oncogenic phenotypes

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Signal Transduction and Targeted Therapy 2020年第1期5卷 2230-2233页

作者： yi ching esther wan Tsz Chui Sophia Leung Dongbo Ding Xulun Sun Jiaxian Liu Lina Zhu Tze Zhen Evangeline Kang Du Yang Yuchen Zhang Jitian Zhang Chengmin Qian Michael Shing Yan Huen Qing Li Maggie Zi ying Chow Zongli Zheng Junhong Han Ajay Goel Xin wang Toyotaka Ishibashi Kui Ming Chan Department of Biomedical Sciences City University of Hong KongHong KongChina Key Laboratory of Biochip Technology Biotech and Health CentreShenzhen Research Institute of City University of Hong KongShenzhenChina Division of Life Science Hong Kong University of Science and TechnologyHong KongChina State Key Laboratory of Protein and Plant Gene Research School of Life Sciences and Peking-Tsinghua Center for Life SciencesPeking UniversityPekingChina School of Biomedical Sciences The University of Hong KongHong KongChina Ming Wai Lau Centre for Reparative Medicine Karolinska InstitutetHong KongChina State Key Laboratory of Biotherapy and Cancer Center West China HospitalWest China Medical SchoolSichuan UniversitySichuanChina Department of Molecular Diagnostics and Experimental Therapeutics Beckman Research Institute at City of Hope Comprehensive Cancer CenterDuarteCAUSA

Dear Editor,Recent studies from us and others have deciphered the clinical relevance of a variety of oncohistones1 in different diseases.The H3K27M and H3K36M mutant histones exert dominant-negative effects on methylation levels of histone H3K27 and H3K36 on wildtype histone protein in pediatric brain cancers2–4 and chondroblastoma,5,6 respectively.In contrast to H3K27M and H3K36M that act in trans to cause global reduction of methylation at the respective residues,the H3G34 mutations,including H3G34V/R and H3G34W/L found in pediatric high-grade glioma and giant cell tumor of the bone,affect the H3K36 methylation in cis and alter the H3K36 methylation on the nucleosome containing the H3G34 mutation(s).

关键词： Cancer clinical pediatric

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Relationship between use of selective serotonin reuptake inhibitors and irritable bowel syndrome: A populationbased cohort study

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World Journal of Gastroenterology 2017年第19期23卷 3513-3521页

作者： wan-Tzu Lin yi-Jun Liao Yen-Chun Peng Chung-Hsin Chang ching-Heng Lin Hong-Zen Yeh Chi-Sen Chang Division of Gastroenterology and Hepatology Department of Internal MedicineTaichung Veterans General Hospital Division of Gastroenterology and Hepatology Department of Internal MedicinePuli Branch of Taichung Veterans General Hospital Faculty of Medicine College of MedicineNational Yang-Ming University Taichung Veteran General Hospital

AIM To investigate the relationship between selective serotonin reuptake inhibitor(SSRI)use and the subsequent development of irritable bowel syndrome(IBS).METHODS This retrospective,observational,population-based cohort study collected data from Taiwan’s National Health Insurance Research Database.A total of 19653patients newly using SSRIs and 78612 patients not using SSRIs,matched by age and sex at a ratio of 1:4, were enrolled in the study from January 1,2000 to December 31,2010.The patients were followed until IBS diagnosis,withdrawal from the National Health Insurance system,or the end of 2011.We analyzed the effects of SSRIs on the risk of subsequent IBS using Cox proportional hazards regression models.RESULTS A total of 236 patients in the SSRI cohort(incidence,2.17/1000 person-years)and 478 patients in the comparison cohort(incidence,1.04/1000 person-years)received a new diagnosis of IBS.The mean follow-up period from SSRI exposure to IBS diagnosis was 2.05years.The incidence of IBS increased with advancing age.Patients with anxiety disorders had a significantly increased adjusted hazard ratio(a HR)of IBS(a HR=1.33,95%CI:1.11-1.59,P=0.002).After adjusting for sex,age,urbanization,family income,area of residence,occupation,the use of anti-psychotics and other comorbidities,the overall a HR in the SSRI cohort compared with that in the comparison cohort was1.74(95%CI:1.44-2.10;Pwan.

关键词：大脑勇气轴急躁的肠症候群选择血清素举起禁止者

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Dynamics of cytokines predicts risk of hepatocellular carcinoma among chronic hepatitis C patients after viral eradication

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World Journal of Gastroenterology 2022年第1期28卷 140-153页

作者： Ming-ying Lu Ming-Lun Yeh ching-I Huang Shu-Chi wang yi-Shan Tsai Pei-Chien 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 Shinn-Cherng Chen Chung-Feng Huang Jee-Fu Huang Chia-Yen Dai wan-Long Chuang Ming-Lung Yu Hepatitis Center and Hepatobiliary Division Department of Internal MedicineKaohsiung Medical University HospitalKaohsiung 80708Taiwan School of Medicine and Hepatitis Research Center College of MedicineCenter for Cancer Research and Center for Liquid BiopsyKaohsiung Medical UniversityKaohsiung 80708Taiwan Department of Medical Laboratory Science and Biotechnology Kaohsiung Medical UniversityKaohsiung 80708Taiwan Health Management Center Department of Community MedicineKaohsiung Medical University HospitalKaohsiung 80708Taiwan Institute of Biomedical Sciences National Sun Yat-Sen UniversityKaohsiung 80708Taiwan

BACKGROUND Chronic hepatitis C virus(HCV)infection induces profound alterations in the cytokine and chemokine signatures in peripheral blood.Clearance of HCV by antivirals results in host immune modification,which may interfere with immune-mediated cancer surveillance.Identifying HCV patients who remain at risk of hepatocellular carcinoma(HCC)following HCV eradication remains an unmet need.We hypothesized that antiviral therapy-induced immune reconstruction may be relevant to HCC development.AIM To investigate the impact of differential dynamics of cytokine expression on the development of HCC following successful antiviral therapy.METHODS One hundred treatment-naïve HCV patients with advanced fibrosis(F3/4)treated with direct-acting antivirals(DAAs)or peginterferon/ribavirin who achieved sustained virologic response[SVR,defined as undetectable HCV RNA throughout 12 wk(SVR12)for the DAA group or 24 wk(SVR24)for the interferon group after completion of antiviral therapy]were enrolled since 2003.The primary endpoint was the development of new-onset HCC.Standard HCC surveillance(abdominal ultrasound andα-fetoprotein)was performed every six months during the followup.Overall,64 serum cytokines were detected by the multiplex immunoassay at baseline and 24 wk after end-of-treatment.RESULTS HCC developed in 12 of the 97 patients over 459 person-years after HCV eradication.In univariate analysis,the Fibrosis-4 index(FIB-4),hemoglobin A1c(HbA1c),the dynamics of tumor necrosis factor-α(TNF-α),and TNF-like weak inducer of apoptosis(TWEAK)after antiviral therapy were significant HCC predictors.The multivariate Cox regression model showed thatΔTNF-α(≤-5.7 pg/mL)was the most important risk factor for HCC(HR=11.54,95%CI:2.27-58.72,P=0.003 in overall cases;HR=9.98,95%CI:1.88-52.87,P=0.007 in the interferon group).An HCC predictive model comprising FIB-4,HbA1c,ΔTNF-α,andΔTWEAK had excellent performance,with 3-,5-,10-,and 13-year areas under the curve of 0.882,0.864,0.903,and 1.000,respectively.The 5-year accumulative risks of HCC

关键词： Hepatitis C virus Hepatocellular carcinoma Sustained virologic response Tumor necrosis factor-α Tumor necrosis factor-like weak inducer of apoptosis Cytokine

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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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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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"Defective" mutations of hepatitis D viruses in chronic hepatitis D patients

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World Journal of Gastroenterology 2005年第11期11卷 1658-1662页

作者： Jaw-ching Wu Sheng-Chieh Hsu Shen-Yung wang yi-Hsiang Huang I-Jane Sheen Hsuan-Hui Shih wan-Jr Syu Institute of Clinical Medicine Department of Medical Research and Education Taipei Veterans General Hospital Taipei Taiwan China Division of Gastroenterology School of Medicine National Yang-Ming University Taipei Taiwan China Institute of Microbiology and Immunology

AIM: To verify whether 'defective' mutations existed in hepatitis D virus (HDV).METHODS: Hepatitis delta antigen (HDAg)-codingsequences were amplified using Pfu DNA polymerases with proof-reading activities from sera of five patients with chronic hepatitis D. Multiple colonies were sequenced for each patient. Pfu analyzed a total of 270 HDV clones.Three representative defective HDV clones were constructed in expression plasmids and transfected into a human hepatoma cell line. Cellular proteins were extracted and analyzed by Western blot.RESULTS: Four of five cases (80%) showed defective HDV genomes in their sera. The percentage of defective genomes was 3.7% (10/270). The majority (90%) of the defective mutations were insertions or deletions that resulted in frameshift and abnormal stop translation of the HDAg. The predicted mutated HDAg ranged from 45amino acids to ＞214 amino acids in length. Various domains of HDAg associated with viral replication or packaging were affected in different HDV isolates. Western blot analysis showed defected HDAg in predicted positions.CONCLUSION: 'Defective' viruses do exist in chronic HDV infected patients, but represented as minor strains. The clinical significance of the 'defected' HDV needs further study to evaluate.

关键词： HDV DNA AIM

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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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