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Stem cell-derived hepatocyte therapy using versatile biomimetic nanozyme incorporated nanofiber-reinforced decellularized extracellular matrix hydrogels for the treatment of acute liver failure

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Bioactive Materials 2023年第10期28卷 112-131页

作者： Yuanyuan Jin Jiabin Zhang Yanteng Xu Ke Yi Fenfang Li Huicong Zhou Haixia Wang Hon Fai Chan Yeh-Hsing Lao Shixian Lv Yu Tao Mingqiang Li laboratory of Biomaterials and Translational Medicine Center for NanomedicineThe Third Affiliated HospitalSun Yat-sen UniversityGuangzhou510630China Guangdong Provincial key laboratory of liver Disease research Guangzhou510630China School of Materials Science and Engineering Peking UniversityBeijing100871China Institute for Tissue Engineering and Regenerative Medicine School of Biomedical ScienceThe Chinese University of Hong Kong999077Hong KongChina Department of Pharmaceutical Sciences University at BuffaloThe State University of New YorkBuffaloNY14214USA

Reactive oxygen species(ROS)-associated oxidative stress,inflammation storm,and massive hepatocyte necrosis are the typical manifestations of acute liver failure(ALF),therefore specific therapeutic interventions are essential for the devastating ***,we developed a platform consisting of versatile biomimetic copper oxide nanozymes(Cu NZs)-loaded PLGA nanofibers(Cu NZs@PLGA nanofibers)and decellularized extracellular matrix(dECM)hydrogels for delivery of human adipose-derived mesenchymal stem/stromal cells-derived hepatocyte-like cells(hADMSCs-derived HLCs)(HLCs/Cu NZs@fiber/dECM).Cu NZs@PLGA nanofibers could conspicuously scavenge excessive ROS at the early stage of ALF,and reduce the massive accumulation of pro-inflammatory cytokines,herein efficiently preventing the deterioration of hepatocytes ***,Cu NZs@PLGA nanofibers also exhibited a cytoprotection effect on the transplanted ***,HLCs with hepatic-specific biofunctions and anti-inflammatory activity acted as a promising alternative cell source for ALF *** dECM hydrogels further provided the desirable 3D environment and favorably improved the hepatic functions of *** addition,the pro-angiogenesis activity of Cu NZs@PLGA nanofibers also facilitated the integration of the whole implant with the host ***,HLCs/Cu NZs@fiber/dECM performed excellent synergistic therapeutic efficacy on ALF *** strategy using Cu NZs@PLGA nanofiber-reinforced dECM hydrogels for HLCs in situ delivery is a promising approach for ALF therapy and shows great potential for clinical translation.

关键词： Acute liver failure Nanozyme Hepatocyte-like cells Human adipose-derived mesenchymal stem/stromal cells Electrospun nanofiber

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Efficacy of decoction from Jieduan Niwan formula on rat model of acute-on-chronic liver failure induced by porcine serum

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Journal of Traditional Chinese Medicine 2020年第4期40卷 602-612页

作者： Li Jinxia Zhang Qiuyun Gao Lianyin Du Yuqiong Chen Yu Institute of Traditional Chinese Medicine Diagnosis Hunan University of Chinese MedicineChangsha 410208China Hunan key laboratory of Traditional Chinese Medicine Diagnosis Changsha 410208China School of Traditional Chinese Medicine Capital Medical UniversityBeijing 100069China beijing key laboratory of Traditional Chinese Medicine Collateral Disease Theory research Beijing 100069China Department of artificial liver Beijing You An Hospital Affiliated to Capital Medical UniversityBeijing 100069China

OBJECTIVE:To dynamically observe the efficacy of Jieduan Niwan formula(JDNW)on a rat model of acute-on-chronic liver failure(ACLF).METHODS:Seventy Wistar rats were divided into control group(6 rats),model group(22 rats),JDNW group(21 rats),and SP600125 group(21 rats).13 weeks'porcine serum injection followed with D-galactosamine and lipopolysaccharide joint acute attack was used to establish ACLF *** in JDNW group were orally given JDNW formula for 3 days before acute attack;rats in SP600125 group were injected with SP60012530 min ahead of acute *** were sacrificed respectively at 4,8 and 12 h after model *** aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),Creatinine(CR),blood urea nitrogen(BUN),prothrombin activity(PTA)were examined by biochemical process,Tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),interleukin-10(IL-10),transformed growth factor-beta 1(TGF-β1),High mobility group box-1(HMGB-1),CD3,CD4,CD8 were analyzed by enzyme-linked immunosorbent assay,apoptotic index(AI)was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling staining,expression of Bad,phosphorylated Jun N-terminal kinases(p-JNK)and Cytochrome C(Cyt C)were detected by immunohistochemical analysis,Bax and Bid were detected by Western blot ***:In model group,the levels of ALT,AST,TBIL,CR,BUN,IL-1β,IL-6,IL-10,TGF-β1 and HMGB-1 remarkably increased and PTA decreased compared with control group(P<0.05),as time goes on,ALT,AST,TBIL,CR,BUN,continued to grow,while IL-1β,IL-6,IL-10,HMGB-1,TGF-β1 and PTA gradually decreased;massive necrosis could be seen;the levels of TNF-α,CD3,CD4,CD8,AI,p-JNK,Bax,Bad,Bid and Cyt C increased at 4 h and peaked at 8 h,but decreased at 12 h(P<0.05).JDNW group,by contrast,showed less pathological injury,increased PTA level,and reduced ALT,AST,TBIL,TNF-α,IL-1β,IL-6,IL-10,TGF-β1,HMGB-1,CD3,CD4 and CD8 levels(P<0.05),moreover,the AI and expression o

关键词： Acute-on-chronic liver failure JNK mitogen-activated protein kinases Apoptosis Jieduan Niwan formula

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Traditional Chinese Medicine for the treatment of influenza: a systematic review and Meta-analysis of randomized controlled trials

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Journal of Traditional Chinese Medicine 2014年第5期34卷 527-531页

作者： Chunya Wang Hao Wang Xinying Liu Dongping Xu Yiping Tang Ping Luo Emergency & Critical Care Center Beijing Anzhen HospitalCapital Medical University Medical Information Center Beijing 302 Hospital Traditional Chinese Medicineand Western Medicine Center Beijing 302 Hospital liver failure Therapy and research Center Beijing 302 Hospital

OBJECTIVE: To justify the clinical use of Traditional Chinese Medicine(TCM) in the treatment of ***: MEDLINE, EMBASE, Chinese Biomedical Literature Database, China National Knowledge Infrastructure Database, China Science and Technology Journal Database, Wanfang Database and the Cochrane Database of Systematic Reviews were searched from thedate of inception until January 1,2013, for the literature on treatment of influenza with ***: A total of 7 randomized controlled trials were identified and reviewed. Of these trials, 2 compared a(modified) prescription of TCM with oseltamivir and 5 compared a patent traditional Chinese drug with oseltamivir. Based on the Meta-analysis,compared to oseltamivir, the(modified) prescription had similar effect in defervescence [WMD=5.66, 95% CI(﹣32.02, 43.35), P=0.77] and viral shedding [WMD=﹣ 6.21, 95% CI(﹣84.19, 71.76), P=0.88], and the patent traditional Chinese drug also had similar effect in viral shedding [WMD=﹣ 0.24,95% CI(﹣4.79, 4.31), P=0.92] but more effective in defervescence [WMD=﹣4.65, 95%CI(﹣8.91, ﹣0.38),P=0.03].CONCLUSION: TCM has potential positive effects in the treatment of influenza.

关键词：中国传统医学随机对照试验 Meta分析系统化治疗流感医学文献数据库审查

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Short-Term Efficacy of Treating Hepatitis B Virus-Related Acute-on-Chronic liver failure Based on Cold Pattern Differentiation with Hot Herbs: A Randomized Controlled Trial

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Chinese Journal of Integrative Medicine 2016年第8期22卷 573-580页

作者：郭玉明李丰衣宫嫚张琳王伽伯肖小河李筠赵艳玲王立福张晓锋 China Military Institute of Chinese Materia Medica 302 Military HospitalBeijing 100039China treatment and research Center for Infectious Diseases 302 Military HospitalBeijing 100039China Integrative Medical Center for liver Diseases 302 Military HospitalBeijing 100039China Medical Affairs Novartis Pharma ChinaBeijing 100004China

Objective： To evaluate the clinical efficacy and safety of Yinchen Zhufu Decoction（茵陈术附汤, YCZFD） in the treatment of acute-on-chronic liver failure caused by hepatitis B virus（HBV-ACLF） with cold pattern in Chinese medicine（CM）. Methods： This is a multi-center randomized controlled trial of integrative treatment of CM and Western medicine（WM） for the management of HBV-ACLF patients. A total of 200 HBV-ACLF patients with cold pattern were equally randomly assigned to receive YCZFD and WM（integrative treatment） or WM conventional therapy alone respectively for 4 weeks. The primary end point was the mortality for HBV-ACLF patients. Secondary outcome measures included Model for End-Stage liver disease（MELD） score, liver biochemical function, coagulation function and complications. Adverse events during treatment were reported. Results： The mortality was decreased 14.28% in the integrative treatment group compared with WM group（χ^2=6.156, P=0.013）. The integrative treatment was found to significantly improve the MELD score（t=2.353, P=0.020）. There were statistically significant differences in aspartate transaminase, total bilirubin, indirect bilirubin, direct bilirubin and prothrombin time between the two groups（P〈0.05 or P〈0.01）. The complications of ascites（χ^2=9.033, P=0.003） and spontaneous bacteria peritonitis（χ^2=4.194, P=0.041） were improved significantly in the integrative treatment group. No serious adverse event was reported. Conclusions： The integrative treatment of CM and WM was effective and safe for HBV-ACLF patients with cold pattern in CM. The Chinese therapeutic principle ＂treating cold pattern with hot herbs＂ remains valuable to the clinical therapy.（Trial registration No. Chi CTR-TRC-10000766）

关键词： hepatitis B virus-related acute-on-chronic liver failure mortality Chinese medicine cold pattern Yinchen Zhufu Decoction

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Traditional Chinese medicine diagnosis and treatment based on systematics

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iliver 2023年第4期2卷 181-187页

作者： Zhanhong Wang Danli Wang Wen Liu Zhongxia Wang The State key laboratory of Management and Control for Complex Systems Institute of AutomationChinese Academy of SciencesBeijing 100190 School of artificial Intelligence University of Chinese Academy of SciencesBeijing 100049China beijing Hospital of Traditional Chinese Medicine Capital Medical UniversityBeijing 100010China Department of Nutrition Fifth Medical CenterPLA General HospitalBeijing 100039China

Background:Traditional Chinese Medicine(TCM)is a well-established medical system with a long ***,the overall concept and systematic thinking in TCM are not comprehensively understood and applied in its inheritance and *** This study aims to provide a basic theory for TCM diagnosis using systematics as the guiding *** modern scientific and technological achievements,we aim to explore a new TCM diagnosis ***:We analyzed previous studies on TCM diagnosis and treatment,and reviewed clinical research on TCM diagnosis and treatment from the viewpoint of *** propose a new process model based on systematics for TCM diagnosis and *** is a generalized model that summarizes the process of“establishing an image to express meaning”.Results:The proposed model was implemented in the clinical practice of *** monitored the detailed treatment process of patients in the Department of liver Diseases at beijing *** patient underwent a treatment program that lasted 1 year and 45 days,consisting of 12 iterative cycles,each guided by the proposed diagnostic model and tailored to the patient's evolving *** case study validates the effectiveness of the proposed model in the diagnosis and treatment of liver disease in *** therapeutic efficacy has been validated through the examination of both TCM indicators and Western medical auxiliary *** these,the TCM indicators consist of 2 components:tongue diagnosis and pulse ***,the Western medical auxiliary indicators encompass a range of assessments,including whole blood cell analysis,professional liver function examination,a series of liver function assessments,a high-sensitivity hepatitis B pentathlete test,as well as color Doppler ultrasound evaluations of the liver,bile duct,pancreas,spleen,and assessments of liver elasticity,among other related examination *** conclusion,it is evident that the syndrome of l

关键词： Traditional Chinesemedicine Systematics Diagnosis and treatment model liver disease

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New Algorithm Rules Out Acute-on-chronic liver failure Development within 28 Days from Acute Decompensation of Cirrhosis

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Journal of Clinical and Translational Hepatology 2023年第3期11卷 550-559页

作者： Xiaoting Tang Hai Li Guohong Deng Xin Zheng Xianbo Wang Yan Huang Yanhang Gao Zhongji Meng Zhiping Qian Feng Liu Xiaobo Lu Yu Shi Beiling Li Wenyi Gu Xiaomei Xiang Yan Xiong Yixin Hou Jun Chen Na Gao Sen Luo Liujuan Ji Jing Li Rongjiong Zheng Haotang Ren Jinjun Chen Hepatology Unit Department of Infectious DiseasesNanfang HospitalSouthern Medical UniversityGuangzhouGuangdongChina Department of Gastroenterology Ren Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShang-haiChina Shanghai Institute of Digestive Disease Key Laboratory of Gastroenterology and HepatologyChinese Ministry of Health(Shanghai Jiao Tong University)ShanghaiChina Department of Infectious Diseases Southwest HospitalThird Military Medical University(Army Medical University)ChongqingChina Department of Infectious Diseases Institute of Infection and ImmunologyUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina Center of Integrative Medicine Beijing Ditan HospitalCapital Medical UniversityBeijingChina Department of Infectious Diseases Hunan Key Laboratory of Viral HepatitisXiangya HospitalCentral South UniversityChangshaHunanChina Department of Hepatology The First Hospital of Jilin UniversityChangchunJilinChina Department of Infectious Diseases Hubei Clinical Research Center for Precise Diagnosis and Treatment of Liver CancerTaihe HospitalHubei University of MedicineShiyanHubeiChina Department of liver Intensive Care Unit Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina Department of Infectious Diseases and Hepatology The Second Hospital of Shandong Univer-sityJinanShandongChina Infectious Disease Center The First Affiliated Hospital of Xinjiang Medical UniversityXinjiangChina The State key laboratory for Diagnosis and treatment of Infectious Diseases The First Affiliated Hospital of School of MedicineZhejiang UniversityHangzhouZhejiangChina Collaborative Innovation Center for Diagnosis and treatment of Infectious Disease HangzhouZhejiangChina National Clinical research Center of Infectious Disease HangzhouZhejiangChina Hepatology Unit Zengcheng BranchNanfang HospitalSouthern Medical UniversityGuangzhouGuangdongChina.

Background and Aims:Approximately 10%of patients with acute decompensated(AD)cirrhosis develop acute-on-chronic liver failure(ACLF)within 28 *** cases have high mortality and are difficult to ***,we aimed to establish and validate an algorithm to identify these patients on ***:Hospitalized patients with AD who developed ACLF within 28 days were considered *** dysfunction was defined accord-ing to the chronic liver failure-sequential organ failure as-sessment(CLIF-SOFA)criteria,and proven bacterial infec-tion was taken to indicate immune system dysfunction.A retrospective multicenter cohort and prospective one were used to derive and to validate the potential algorithm,re-spectively.A miss rate of<5%was acceptable for the calcu-lating algorithm to rule out ***:In the deri-vation cohort(n=673),46 patients developed ACLF within 28 *** total bilirubin,creatinine,international normalized ratio,and present proven bacterial infection at admission were associated with the development of *** patients with≥2 organ dysfunctions had a higher risk for pre-ACLF patients[odds ratio=16.58195%confidence interval:(4.271-64.363),p<0.001].In the derivation co-hort,67.5%of patients(454/673)had≤1 organ dysfunction and two patients(0.4%)were pre-ACLF,with a miss rate of 4.3%(missed/total,2/46).In the validation cohort,65.9%of patients(914/1388)had≤1 organ dysfunction,and four(0.3%)of them were pre-ACLF,with a miss rate of 3.4%(missed/total,4/117).Conclusions:AD patients with≤1 organ dysfunction had a significantly lower risk of developing ACLF within 28 days of admission and could be safely ruled out with a pre-ACLF miss rate of<5%.

关键词： liver cirrhosis Prognosis liver failure End-stage liver disease Organ dysfunction scores.

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Complementation of Wild-Type and Drug-Resistant Hepatitis B Virus Genomes to Maintain Viral Replication and Rescue Virion Production under Nucleos(t)ide Analogs

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Virologica Sinica 2019年第4期34卷 377-385页

作者： Chunchen Wu Baolin Li Xiaoyong Zhang Kaitao Zhao Yingshan Chen Yifei Yuan Yan Liu Rongjuan Chen Dongping Xu Xinwen Chen Mengji Lu Department of laboratory Medicine Maternal and Child Health Hospital of Hubei ProvinceTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430070China State key Lab of Virology Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China Institute of Virology University Hospital of Essen45122 EssenGermany University of Chinese Academy of Sciences Beijing 100049China Institute of Infectious Diseases and liver failure research Center Beijing 302 HospitalBeijing 100039China

As the open reading frames of hepatitis B virus(HBV)genomes are overlapping,resistance mutations(MTs)in HBV polymerase may result in stop codon MTs in hepatitis B surface proteins,which are usually detected as a mixed population with wild-type(WT)*** question was raised how the coexistence of nucleos(t)ide analogs(NAs)resistance MTs and WT sequences affects HBV *** the present study,HBV genomes with frequently detected reverse transcriptase(RT)/surface truncation MTs,rtA181T/sW172^*,rtV191I/sW182^*and rtM204I/sW196^*,were phenotypically characterized alone or together with their WT counterparts in different ratios by transient transfection in the absence or presence of *** the absence of Nas,RT/surface truncation MTs impaired the expression and secretion of HBV surface proteins,and had a dose-dependent negative effect on WT HBV virion ***,in the presence of Nas,coexistence of MTs with WT maintained viral replication,and the presence of WT was able to rescue the production of MT HBV *** findings reveal that complementation of WT and MT HBV genomes is highly effective under drug treatment.

关键词： Hepatitis B virus(HBV) Viral replication Nucleos(t)ide analogs resistance mutations Surface truncation mutation

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Plasma exchange-centered artificial liver support system in hepatitis B virus-related acute-onchronic liver failure:a nationwide prospective multicenter study in China

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Hepatobiliary & Pancreatic Diseases International 2016年第3期15卷 275-281页

作者： Jia-Jia Chen Jian-Rong Huang Qian Yang Xiao-Wei Xu Xiao-Li Liu Shao-Rui Hao Hui-Fen Wang Tao Han Jing Zhang Jian-He Gan Zhi-Liang Gao Yu-Ming Wang Shu-Mei Lin Qing Xie Chen Pan Lan-Juan Li State key laboratory for Diagnosis and treatment of Infectious Diseases and Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesFirst Affiliated HospitalZhejiang University School of Medicine liver failure Therapy and research Center 302 Hospital of People’s Liberation Army Department of Hepatology Third Central Clinical College of Tianjin Medical University artificial liver Center You’an HospitalCapital Medical University Department of Infectious Diseases First Affiliated Hospital of Suzhou University Department of Infectious Diseases Third Affiliated Hospital of Sun Yat-Sen University Institute of Infectious Diseases Southwest HospitalThird Military Medical University Department of Infectious Diseases First Affiliated Hospital of Xi’an Jiaotong University Department of Infectious Diseases Ruijin HospitalShanghai Jiaotong University School of Medicine Department of Infectious Diseases Infectious Diseases Hospital Affiliated to Fujian Medical University

BACKGROUND： Plasma exchange （PE）-centered artificial liver support system reduced the high mortality rate of hepa titis B virus （HBV）-related acute-on-chronic liver failure （ACLF）. But the data were diverse in different medical centers. The present prospective nationwide study was to evaluate the effects of PE on patients with HBV-ACLF at different stages.

关键词： liver failure artificial liver support plasma exchange acute-on-chronic liver failure

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Serum HBV RNA predicts HBeAg clearance and seroconversion in chronic hepatitis B patients treated with nucleos(t)ide analogues

Serum HBV RNA predicts HBeAg clearance and seroconversion in...

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第11届全国疑难及重症肝病大会

作者：王扬廖昊邓中平刘燕娜卞丹丹任艳于广鑫蒋莹莹白丽刘霜刘梅周莉陈煜段钟平郑素军鲁凤民 liver disease center Beijing YouAn Hospital Capital Medical University beijing municipal key laboratory of liver failure and artificial liver treatment & research Beijing YouAn Hospital Capital Medical University Department of Microbiology and Infectious Disease Center Peking University Health Science Center Intervention and Cell Therapy Center Peking University Shenzhen Hospital Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center Academy for Advanced Interdisciplinary Studies Peking University Hunan Provincial key laboratory of Gene Diagnostic Technology

Background & Aims: To evaluate the predictive value of serum HBV DNA, HBV RNA,HBcrAg, HBsAg, intrahepatic HBV DNA, and cccDNA for HBeAg clearance and seroconversion during long-term treatment of nucleos(t)ide analogue...

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Guideline of Prevention and treatment for Chronic Hepatitis B (2nd Version)

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Journal of Clinical and Translational Hepatology 2017年第4期5卷 297-318页

作者： Jinlin Hou Guiqiang Wang Fusheng Wang Jun Cheng Hong Ren Hui Zhuang Jian Sun Lanjuan Li Jie Li Qinghua Meng Jingmin Zhao Zhongping Duan Jidong Jia Hong Tang Jifang Sheng Jie Peng Fengmin Lu Qing Xie Lai Wei Chinese Society of Hepatology,Chinese Medical Association Chinese Society of Infectious Diseases,Chinese Medical Association Department of Infectious Diseases Nanfang HospitalSouthern Medical UniversityGuangzhouChina Department of Infectious Diseases Center for Liver DiseasesPeking University First HospitalBeijingChina The Institute of Translational Hepatology 302 Hospital of PLAPeking UniversityBeijingChina Center of liver Diseases Beijing Ditan HospitalCapital Medical UniversityBeijingChina Institute for Viral Hepatitis the Key Laboratory of Molecular Biology for Infectious Diseasesthe second Affiliated Hospital of Chongqing Medical UniversityChongqingChina Department of Microbiology of Peking University Health Science Center BeijingChina State key laboratory for Diagnosis and treatment of Infectious Diseases Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseasesthe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouChina Serious Illness Medicine Inpatient Area Beijing Youan HospitalCapital Medical UniversityBeijingChina Department of Pathology 302 Hospital of PLAPeking UniversityBeijingChina artificial liver Center Beijing Youan HospitalCapital Medical UniversityBeijingChina liver research Center Beijing Friendship HospitalCapital Medical UniversityBeijingChina Center of Infectious Diseases West China Hospital of Sichuan UniversityDivision of Infectious DiseasesState Key Laboratory of BiotherapySichuan UniversityChengduChina Department of Infectious Diseases Shanghai Jiao Tong University School of Medicine Affiliated Ruijin HospitalShanghaiChina Hepatology Institute Peking University People's HospitalBeijingChina 不详

This guideline is established to standardize the prevention,diagnosis and antiviral therapy of chronic hepatitis B(CHB).For other treatment regimens and methods involving CHB,please refer to relevant guidelines and *** Chinese Society of Hepatology,Chinese Medical Association(CMA)and the Society of Infectious Diseases,CMA organized relevant native experts to establish this Guideline of Prevention and treatment for Chronic Hepatitis B(1st version)in 2005,and made the first revision in *** the past 5 years,great progress has been made in the native and foreign fundamental and clinical research with respect to CHB,necessitating additional revision of this guideline.

关键词： Hepatitis B Chronic treatment Prevention Guideline

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