替比夫定和拉米夫定治疗乙肝肝硬化病人的有效性和安全性

肝胆速递

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2893.2012.01600.x/abstract
Randomized clinical trial: efficacy and safety of telbivudine and lamivudine in treatment-naïve patients with HBV-related decompensated cirrhosis随机对照临床试验：替比夫定和拉米夫定治疗乙肝相关肝硬化病人的有效性和安全性

    H. L.Y. Chan1,
    Y. C. Chen2,
    E. J. Gane3,
    S. K. Sarin4,
    D. J. Suh5,
    T. Piratvisuth6,
    B. Prabhakar7,
    S. G. Hwang8,
    G. Choudhuri9,
    R. Safadi10,
    T. Tanwandee11,
    A. Chutaputti12,
    C. Yurdaydin13,
    W. Bao14,
    C. Avila15,
    A. Trylesinski15

Article first published online: 15 MAR 2012

DOI: 10.1111/j.1365-2893.2012.01600.x

    1    Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
    2    Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan
    3    Liver Unit, Auckland City Hospital, Auckland, New Zealand
    4    Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
    5    Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
    6    NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand
    7    Osmania Medical College and General Hospital, Hyderabad, India
    8    Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea
    9    Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
    10    Holy Family Hospital, Nazareth & Hadassah Medical Center, Jerusalem, Israel
    11    Siriraj Hospital, Bangkok, Thailand
    12    Phramongkutklao Hospital, Bangkok, Thailand
    13    University of Ankara Medical School, Ankara, Turkey
    14    Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA
    15    Novartis Pharma AG, Basel, Switzerland

*Dr Henry Lik-Yuen Chan, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 9/F Prince of Wales Hospital, 30–32 Ngan Shing Street, Shatin, Hong Kong SAR, China. E-mail: [email protected]

Summary.  Patients with decompensated cirrhosis owing to chronic hepatitis B viral (HBV) infection have a high morbidity/mortality rate, and the treatment remains a challenge. We studied the safety and efficacy of telbivudine and lamivudine in such patients. This noninferiority, double-blind trial randomized 232 treatment-naive patients with decompensated HBV (1:1) in 80 academic hospitals to receive once-daily telbivudine 600 mg or lamivudine 100 mg for 104 weeks. Primary composite endpoint was proportion of patients with HBV DNA <10 000 copies/mL, normal alanine aminotransferase (ALT) and Child-Turcotte-Pugh score improvement/stabilization at week 52. Response rates using a post hoc modified endpoint (HBV DNA <300 copies/mL [57 IU/mL] and ALT normalization) in intent-to-treat analysis (missing = failure) were 56.3%vs 38.0% after 76 weeks (P = 0.018) and 45.6%vs 32.9% after 104 weeks (P = 0.093) for telbivudine vs lamivudine. Telbivudine treatment was an independent predictive factor for HBV DNA <300 copies/mL and ALT normalization (P = 0.037). Response rates with protocol-defined composite endpoint in intent-to-treat analysis (M = F) were 56.2 vs 54.0% (noninferiority not achieved) and 39.1%vs 36.4% (noninferiority achieved) in telbivudine and lamivudine groups at 52 and 104 weeks. Telbivudine treatment was associated with a significant improvement in glomerular filtration rate compared to lamivudine treatment and was also associated with a trend for improvement in survival (87%vs 79%). No cases of lactic acidosis were reported. Telbivudine compared to lamivudine was associated with a higher rate of patients with both viral suppression and ALT normalization, a trend towards a higher rate of survival and significant improvement in glomerular filtration.

肝胆速递

随机临床试验的疗效和安全性的替比夫定和拉米夫定在治疗初治患者与HBV相关的肝硬化失代偿期

    H. L.Y. CHAN1，
    Y. C.臣2，
    E. J. Gane3，
    S. K. Sarin4，
    D. J. Suh5，
    T. Piratvisuth6，
    B. Prabhakar7
    S. G. Hwang8，
    G. Choudhuri9，
    R. Safadi10，
    T. Tanwandee11，
    A. Chutaputti12，
    C. Yurdaydin13，
    W. Bao14，
    C. Avila15，
    A. Trylesinski15

在网上公布：2012年3月15号

DOI：10.1111/j.1365-2893.2012.01600.x

    内科及药物治疗学系，香港，香港中文大学，中国
    2肝病研究单位，长庚医院，长庚大学医学院，台北，台湾
    3肝单位，奥克兰，新西兰奥克兰市医院，
    4部肝病，肝及胆道科学，新德里，印度
    5系，首尔，韩国蔚山大学医学院峨山医学中心，内科，
    胃肠病学和肝病学研究所6 NKC，Songklanagarind医院，宋卡王子大学，泰国合艾（Hat Yai）
    7奥斯马尼亚医学院和医院，海得拉巴，印度
    8内科，CHA CHA盆唐医学中心大学，城南，韩国
    9桑贾伊·甘地研究生医学科学研究所，印度勒克瑙，
    10圣家医院，拿撒勒，以色列耶路撒冷哈达萨医疗中心，
    11，泰国曼谷Siriraj医院，
    12 Phramongkutklao医院，曼谷，泰国
    13安卡拉大学医学院，土耳其安卡拉
    14瑞士诺华制药公司，东汉诺威，NJ，USA
    15，瑞士巴塞尔的诺华制药公司，

博士亨利力源生，内科及药物治疗学系，中国香港大学，9 / F王子，中国，香港特区，沙田威尔斯亲王医院，沙田银城街30-32号。电子邮件：[email protected]

总结。由于慢性乙型肝炎病毒（HBV）感染的肝硬化失代偿期的患者有很高的发病率/死亡率和治疗仍然是一个挑战。我们研究了在这些患者中，替比夫定和拉米夫定的安全性和有效性。非劣效性，双盲随机试验232治疗初治患者与失代偿期乙型肝炎病毒（1:1），在80余医院接受每日一次的替比夫定或拉米夫定600毫克100毫克104周。主要复合终点为患者HBV DNA <000拷贝/毫升，正常的谷丙转氨酶（ALT）和儿童特科特-Pugh分级评分改善/稳定在52周的比例。响应率，采用事后修改端点（HBV DNA <300拷贝/ mL [57 IU /毫升]，ALT复常）在意向性治疗分析（缺少=故障）经过76周分别为56.3％和38.0％（P = 0.018），45.6％和32.9％，后104周（P = 0.093），替比夫定与拉米夫定。替比夫定治疗HBV DNA <300拷贝/ ml和ALT复常率（P = 0.037）的独立预测因素。响应率与协议定义的复合终点在意向性治疗分析（M = F）分别为56.2和54.0％（未达到非劣效性）和39.1％比36.4％（非劣效性实现）替比夫定和拉米夫定组在52周和104周。与一个显着的改善肾小球滤过率相比，拉米夫定治疗，提高生存率（87％对79％）的趋势也与替比夫定治疗。没有发生乳酸性酸中毒的报道。替比夫定较拉米夫定伴随着较高的患者抑制病毒和ALT正常化，生存和显着改善肾小球滤过率较高的趋势。