单位：[1]State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou[2]Department of Infectious Diseases, Guangdong General Hospital, Guangzhou广东省人民医院[3]Beijing Ditan Hospital, Capital Medical University[4]Beijing Youan Hospital, Capital Medical University[5]Liver Research Center, Beijing Friendship Hospital, Capital Medical University临床科室国家中心肝病分中心首都医科大学附属北京友谊医院[6]Department of Microbiology and Infectious Disease Center, Peking University Health Science Center[7]Hepatology Unit, Peking University People’s Hospital[8]Department of Infectious Diseases, First Hospital of Peking University, Beijing[9]Department of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical University, Xi’an[10]Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning[11]Department of Infectious Diseases, The First People Hospital of Foshan, Foshan[12]Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu四川大学华西医院[13]Department of Infectious Diseases, Zhejiang University 1st Affiliated Hospital, Hangzhou浙江大学医学院附属第一医院[14]The 6th People’s Hospital, Hangzhou[15]Jinan Infectious Diseases Hospital, Ji’nan[16]Hepatology Unit, No. 1 Hospital Affiliated to Jilin University, Changchun[17]Department of Infectious Diseases, Second Affiliated Hospital, Chongqing Medical University, Chongqing[18]Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang,中国医科大学附属盛京医院[19]Department of Infectious Diseases, Changhai Hospital, The Second Military Medical University[20]Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine[21]Department of Infectious Diseases, Huashan Hospital, Fudan University,[22]Department of Infectious Diseases, 85th People’s Liberation Army Hospital, Shanghai[23]Liver Center, First Affiliated Hospital of Fujian Medical University, Fuzhou[24]Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan华中科技大学同济医学院附属同济医院[25]Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, China
Background and AimData about the efficacy of de novo combination therapies, or optimization strategy by adding the other drug based on the virological response at week 24 of low genetic barrier antiviral agents is still limited. This study aimed to compare the efficacy at week 104 of lamivudine monotherapy (MONO), lamivudine plus adefovir dipivoxil (ADV) combination therapy (COMBO), and lamivudine optimization strategy (OPTIMIZE). MethodsAdult patients without antiviral therapy within 6 months before screening with hepatitis B virus (HBV)-DNA10(5) copies/mL, alanine aminotransferase 1.3-10 times upper limit of normal and compensated hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) were randomized into three groups with 1:1:1 ratio. Patients in OPTIMIZE group started with lamivudine 100mg q.d., and ADV 10mg q.d. was added to suboptimal responders (HBV-DNA >1000 copies/mL at week 24) from week 30 to week 104, whereas patients with early virological response (HBV-DNA1000 copies/mL at week 24) continued MONO until week 104. For all the patients receiving MONO, ADV would be added if virological breakthrough was confirmed. ResultsAt week 104, more patients in COMBO and OPTIMIZE groups achieved HBV-DNA<300 copies/mL (53.3% [64/120] and 48.3% [58/120]), with less lamivudine resistance (0.8% and 6.7%) compared with MONO group (HBV-DNA<300 copies/mL 34.8% [41/118], lamivudine resistance 58.5%). Patients under MONO with early virological response showed superior efficacy at week 104 (HBV-DNA<300 copies/mL 73.1% [38/52], HBeAg seroconversion 40.4% [21/52]). All regimens were well tolerated. ConclusionCombination therapy of lamivudine plus ADV exhibited effective viral suppression and relatively low resistance in HBeAg-positive CHB patients. In lamivudine-treated patients with suboptimal virological response at week 24, promptly adding on ADV is necessary to prevent resistance development.
基金：
National Science and Technology Major Project of China [2012ZX10002003]
第一作者单位：[1]State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou
通讯作者：
通讯机构：[1]State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou[*1]Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University,Guangzhou 510515, China
推荐引用方式(GB/T 7714)：
Liang Xieer,Cheng Jun,Sun Yongtao,et al.Randomized, three-arm study to optimize lamivudine efficacy in hepatitis B e antigen-positive chronic hepatitis B patients[J].JOURNAL of GASTROENTEROLOGY and HEPATOLOGY.2015,30(4):748-755.doi:10.1111/jgh.12835.
APA：
Liang, Xieer,Cheng, Jun,Sun, Yongtao,Chen, Xinyue,Li, Tong...&Hou, Jinlin.(2015).Randomized, three-arm study to optimize lamivudine efficacy in hepatitis B e antigen-positive chronic hepatitis B patients.JOURNAL of GASTROENTEROLOGY and HEPATOLOGY,30,(4)
MLA：
Liang, Xieer,et al."Randomized, three-arm study to optimize lamivudine efficacy in hepatitis B e antigen-positive chronic hepatitis B patients".JOURNAL of GASTROENTEROLOGY and HEPATOLOGY 30..4(2015):748-755
