EASL2012: Entecavir treament - 2 Abstracts

StephenW

Abstract               
                                

Title	Maintained viral suppression and excellent safety profile of entecavir monotherapy in 418 NUC-naïve patients with chronic hepatitis B : a 4-year field practice, multicenter study
Speaker:	Pietro   Lampertico
Author:	P. Lampertico1*, R. Soffredini1, F. Invernizzi1, M. Viganò2, F. Facchetti1, E. Minola3, O. Fracassetti4, F. Suter4, S. Zaltron5, A. Vavassori5, G. Carosi5, E. Angeli6, G. Gubertini6, C. Magni6, A. Testa7, G. Antonucci7, M. Vinci8, G. Pinzello8, E. Fatta9, S. Fargion9, P. Del Poggio10, B. Coco11, M. Brunetto11, M. Andreoletti12, A. Colli12, M. Fasano13, T. Santantonio14, G. Colloredo15, L. Pasulo16, S. Fagiuoli16, A.E. Colombo17, G. Bellati17, F. Fumagalli Maldini18, M. Milanese18, M. Pozzi19, N. Terreni20, G. Spinzi20, M. Quagliuolo21, M. Borzio21, G. Lunghi22, M. Colombo1
Affiliation:	11st Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, 2U.O. Epatologia, Ospedale San Giuseppe, Università degli Studi di Milano, Milan, 3Servizio Malattie Epatiche e Infettive, Humanitas Gavazzeni, 4Infectious Diseases, Ospedali Riuniti di Bergamo, Bergamo, 5II Divisione Malattie Infettive, Azienda Ospedaliera Spedali Civili, Brescia, 6I and II Division Infectious Diseases, Ospedale Luigi Sacco, Milan, 7INMI, IRCCS L. Spallanzani, Roma, 8SC Epatologia e Gastroenterologia, Ospedale Niguarda Cà Granda, 9Internal Medicine 1b, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, 10U.O. Epatologia, Ospedale di Treviglio, Treviglio, 11U.O. Epatologia, Azienda Ospedaliero Universitaria Pisana, Pisa, 12S.C. Medicina Generale, Ospedale A. Manzoni, Lecco, 13Clinic of Infectious Diseases, Università di Bari, Bari, 14Clinic of Infectious Diseases, Università di Foggia, Foggia, 15Division of Medicine, Policlinico San Pietro, Ponte San Pietro, 16Gastroenterology Unit, Liver and Lung Transplantation Center, Ospedali Riuniti di Bergamo, Bergamo, 17Unità Operativa di Medicina, Servizio di Epatologia, Ospedale Sant'Anna, Como, 18Liver Center, Clinica Medica, Azienda Ospedaliera San Gerardo, Università Milano Bicocca, Monza, 19U.O. Medicina, Ospedale Fatebenefratelli, Erba, 20U.O. Gastroenterologia, Ospedale Valduce, Como, 21U.O. Gastroenterologia, Azienda Ospedaliera di Melegnano, Melegnano, 22Istituto di Medicina Preventiva, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy. *[email protected]
Aim: Aim of the studywas to assess the long term effectiveness and safety of Entecavir (ETV)monotherapy in NUC-naïve patients. Methods: 418 consecutive NUC-naïve patients with CHBwere recruited in 21 Liver Units in Italy and treated with ETV 0.5 mg for 42months (2-53). At baseline, age was 58 years, 76% males, 83% HBeAg-negative, HBVDNA 6.0 log IU/ml, 85% with elevated ALT, 49% cirrhotics, 56% with concomitantdiseases/medications. Liver function tests and HBV DNA, were assessed by asensitive assays every 3 months. Virological breakthrough was defined as > 1log U increase of viremia, a “blip” was the occurrence of detectable viremia(< 100 IU/ml) in a virological responder. Results: The rates of undetectable HBV DNA, progressively increasedover time, from 85% at year 1, 95% at year 2, 96% at year 3 and 99% at year 4.A primary non response occurred in 1%, a partial response at week 48 in 12%, ablip of viremia in 11%, a virological breakthrough in 4% and drug resistance in< 1% of the patients. HBeAg seroconversion and HBsAg loss rates progressivelyincreased up to 56% and 21% at year 4, respectively. ALT levels became normalin 90% of patients. Among 164 cirrhotics, the 4-year cumulative probability ofHCC development was 10%. No safety issues were reported. Serum creatinineremained unchanged during treatment [from 0.90 (0.50-9.0) at baseline vs 0.91(0.47-8.0) mg/dl at year 4] as well as the proportion of patients with serumcreatinine > 1.5 mg/dl (2% at baseline vs 2% at year 4). Less than 1% of thepatients showed > 0.5 mg increase of creatinine and/or < 2 mg/dl ofphosphorus or significant proteinuria. Overall, 6% of the patients died, 3%were transplanted, 6% required treatment adaptation (PEG or ETV+TDF), 2%stopped ETV following HBsAg clearance and 8% were lost to follow-up. Conclusion: HBV replication wasefficiently suppressed during 4 years of ETV monotherapy in most patients inthe context of an excellent safety profile. Hepatocellular carcinoma, not clinicaldecompensation, continued to occur in cirrhotic patients.

StephenW

标题维修抑制病毒在418国统会的天真与慢性乙型肝炎患者，恩替卡韦单一卓越的安全性：一项为期4年的野外实习，多中心研究
主讲人：彼得Lampertico
作者：P. Lampertico1 *，河Soffredini1，Invernizzi1楼，M.Viganò2，楼Facchetti1 E. Minola3，澳Fracassetti4，Suter4楼，与Zaltron5 A Vavassori5，G。Carosi5，Angeli6大肠杆菌A. Testa7，G。Antonucci7，研究Vinci8研究Pinzello8，大肠杆菌Fatta9研究Fargion9，P.德尔Poggio10，B Coco11，M. Brunetto11，研究Andreoletti12 Magni6，C，G。Gubertini6 A. Colli12，研究Fasano13，Santantonio14吨，Colloredo15 G。，属Pasulo16，与Fagiuoli16，曝光Colombo17，G。Bellati17，FUMAGALLI楼Maldini18，研究Milanese18，研究Pozzi19，北Terreni20，G。 spinzi20，Quagliuolo21研究，M. Borzio21，G. Lunghi22，Colombo1研究
单位：安防行业的胃肠科，中基金会IRCCS CA格兰达Ospedale Maggiore的Policlinico，Universitàdegli Studi米兰，2U.O. epatologia，Ospedale圣朱塞佩，Universitàdegli Studi米兰，AC米兰，3Servizio Malattie EpaticheéInfettive，Humanitas Gavazzeni，4Infectious疾病，Ospedali里尤尼蒂工厂DI贝加莫，贝加莫，5II Divisione Malattie Infettive，Azienda Ospedaliera Spedali Civili，布雷西亚，6I和二部传染病疾病，Ospedale路易吉·萨科，米兰，7INMI，IRCCS研究斯帕兰扎尼，罗马，8SC EpatologiaéGastroenterologia，Ospedale Niguarda CA格兰达，9Internal医药1B的Fondazione IRCCS CA的格兰达Ospedale Maggiore Policlinico，Universitàdegli Studi米兰，米兰，10U.O 。 epatologia，Ospedale DI TREVIGLIO，TREVIGLIO，11U.O. epatologia，Azienda Ospedaliero Universitaria Pisana，比萨，12S.C. MEDICINA兴业，Ospedale答曼佐尼，莱科，13ClinicUniversità迪巴里，巴里传染病的传染病，Università迪福贾，福贾，医学15Division，Policlinico圣彼得，圣彼得浦16Gastroenterology单位，肝，肺14Clinic器官移植中心，DI贝加莫Ospedali里尤尼蒂工厂，贝加莫，17UnitàOperativa DI MEDICINA，Servizio DI Epatologia，Ospedale圣安娜，科莫，18Liver中心，Clinica药物，Azienda Ospedaliera圣赫拉尔，Università米兰比可卡，蒙扎，19U.O. MEDICINA，Ospedale Fatebenefratelli，尤尔巴，20U.O. gastroenterologia，Ospedale Valduce，科摩，21U.O. ，gastroenterologia，DI Melegnano Azienda Ospedaliera，Melegnano，22Istituto的DI MEDICINA Preventiva的Fondazione IRCCS CA的格兰达Ospedale Maggiore Policlinico，Universitàdegli Studi米兰，米兰，意大利。 * pietro.lampertico @ unimi.it
目的：研究的目的是评估在国统会，初治患者，恩替卡韦（ETV）单药治疗的长期有效性和安全。
方法：连续418国统会，初治患者，慢性乙型肝炎21日在意大利的肝单位招聘和教育电视节目为42个月（2-53）0.5毫克治疗。在基线，年龄为58​​岁，76％为男性，83％，HBeAg阴性，HBV DNA的日志6.0 IU /毫升，85％ALT升高，49％的肝硬化患者，56％伴发疾病/药物。敏感的检测由每3个月，肝功能试验和HBV DNA，进行了评估。病毒学突破定义为> 1log的U血症增加，“昙花一现”是在病毒学应答（<100 IU /毫升）检测血症的发生。
结果：乙型肝炎病毒DNA检测不到率，随着时间的推移逐步增加，从85％在1年，2年的95％，96％在3年和4年的99％。一个非主要反应发生在1％，在48周的12％部分缓解，11％的病毒血症昙花一现，在4％和<1％的患者在耐药病毒学突破。 HBeAg血清转换和HBsAg转阴率逐步上升到4年的56％和21％，分别。 90％的患者ALT水平恢复正常。其中164肝硬化，肝癌发展的4年累积概率为10％。没有安全问题的报道。血清肌酐在治疗过程中保持不变[0.90（0.50-9.0）在基线和0.91（0.47-8.0）mg / dl的在今年4]以及患者的血清肌酐> 1.5 mg / dl的基线（2％的比例相较于在4年的2％）。不到1％的患者显示> 0.5毫克肌酐增加和/或<2毫克/升，磷或明显蛋白尿。总体而言，6％的患者死亡，3％，6％的移植治疗所需适应（PEG或ETV+华盈），2％，停止ETV后，HBsAg清除和8％，失去了跟进。
结论：在大多数患者在一个很好的安全性方面的ETV单一的4年中得到了有效抑制乙肝病毒复制。肝癌，而不是临床失代偿，继续发生在肝硬化患者。

StephenW

Abstract               
                                

Title	Lamivudine and Entecavir treatment in patients with chronic hepatitis B liver failure: a large, multicenter, placebo controlled, prospective study in China
Speaker:	Lanjuan   Li
Author:	Y. Yang1, J. Huang1, H. Jia1, Q. Xie2, Z. Gao3, Y. Wang4, Z. Duan5, H. Wang6, S. Lin7, T. Hao8, J. Gan9, C. Pan10, L. Li1*, Chinese Study Group for HBV Related Liver Failure
Affiliation:	1Dept. of Infectious Diseases, 1st Affiliated Hospital of Zhejiang University, Hangzhou, 2Dept. of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University, Shanghai, 3Dept. of Infectious Diseases, 1st Affiliated Hospital of Sun Yat-sen University, Guangzhou, 4Dept. of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, 5Beijing Youan Hospital, Capital Medical University, 6302 Military Hospital, Beijing, 7The First Affiliated Hospital of Medical College of Xi’an Jiao Tong University, Xi'an, 8Tianjin Third Central Hospital, Tianjin, 9The First Affiliated Hospital of Suzhou University, Suzhou, 10Affiliated Infectious Hospital of Fujian Medical University, Fuzhou, China. *[email protected]
Background and aim: Currently there is a lack of large cohort study to demonstrate the effectiveness of antiviral treatment for chronic hepatitis B liver failure. There is no head-to-head study to compare the efficacy of lamivudine, entecavir and placebo in patients with chronic hepatitis B liver failure. Method: We consecutively enrolled 931 patients with chronic hepatitis B liver failure, among them a total of 315 patients refused to sign an informed consent form to receive nucleoside analogue treatment were served as control. 326 patients received lamivudine treatment and 290 patients received entecavir treatment. The relationship between baseline HBV DNA levels and 12-week mortality rate of patient chronic hepatitis B liver failure was firstly investigated. The cumulative survival rate during 12-week follow-up of three groups was evaluated. Results: Firstly our results clearly indicated that the cumulative mortality rate of chronic hepatitis B liver failure was highly associated with serum HBV DNA levels. Besides the HBV DNA levels, the high baseline bilirubin levels, high INR values, low platelet numbers, and cirrhosis were found to be significantly related to mortality of these group of patients. Lamivudine and entecavir treatment significantly reduce HBV DNA level from 8 weeks than that of in placebo group, but there were no significant difference between lamivudine and entecavir group. The number of patients in lamivudine and entecavir group with undetectable HBV DNA was 30.5% and 36.6% at week 12 respectively, there was significant difference between two groups (P< 0.05). . Among patients with HBeAg positive diseases, 45.3% patients in lamivudine group and 44.7% in entecavir group lost HBeAg at follow up week 12 respectively, whereas none in placebo group. 36.0% patients in lamivudine group and 34.2% in entecavir group had HBeAg seroconversion at week 12, while none of patient in placebo had HBeAg seroconversion at follow up period. Conclusion: Antiviral treatment therapy can significantly reduce the mortality of patients with chronic hepatitis B liver failure. Both lamivudine and entecavir can be prescribed as an initial treatment in patients with chronic hepatitis B liver failure to reduce the mortality.

StephenW

标题拉米夫定和恩替卡韦治疗慢性乙型肝炎肝功能衰竭患者：一个大型，多中心，安慰剂对照，在中国的前瞻性研究
主讲人：李Lanjuan
作者：Y，Z。Gao3 J。Huang1，H. Jia1，问Xie2，Wang4华，Duan5 Z。，H。Wang6，Lin7与，Hao8吨，Gan9研究，Pan10三洋1，，研究LI1 *中国研究小组，为HBV相关肝功能衰竭
单位：1Dept。传染病，第一附属医院，浙江大学，杭州，2Dept。传染病，瑞金医院，上海交通大学，上海，3Dept。传染病，第一附属医院，广州，4Dept孙中山大学。对传染病，西南医院，第三军医大学，重庆，5Beijing 6302军区总医院，佑安医院，首都医科大学，北京，第七西安交通大学，西安医学院第一附属医院，第三代中央8Tianjin医院，天津，第九条第一附属医院，苏州大学，苏州，福建医科大学，福州，中国10Affiliated传染病医院。 * [email protected]
背景和目的：目前还缺乏一个大型的队列研究，以证明抗病毒药物治疗慢性乙型肝炎肝功能衰竭的有效性。没有头的研究，比较拉米夫定，恩替卡韦和安慰剂的疗效与慢性乙型肝炎肝功能衰竭患者。
方法：我们连续入选931例慢性乙型肝炎肝功能衰竭，其中共有315例患者拒绝签署知情同意书，接受核苷类似物治疗作为对照。 326例接受拉米夫定治疗290例患者接受恩替卡韦治疗。基线HBV DNA水平和12周的病人慢性乙型肝炎肝功能衰竭的死亡率之间的关系，首先考察。三组的累积生存率在12周的后续率进行了评估。
结果：首先我们的研究结果清楚地表明，慢性乙型肝炎肝功能衰竭的累积死亡率高与血清HBV DNA水平相关。除了发现这些患者的死亡率显着相关的HBV DNA水平，高基线胆红素水平，INR值高，低血小板数，肝硬化。拉米夫定和恩替卡韦治疗8周高于安慰剂组显着降低HBV DNA水平，但也有拉米夫定和恩替卡韦组之间没有显着性差异。拉米夫定和恩替卡韦组患者检测不到HBV DNA的数量为30.5％和36.6％，分别在12周有显着性差异两组（P <0.01）。 。在HBeAg阳性的疾病，在拉米夫定组的45.3％的患者和44.7％恩替卡韦组患者失去随访12周时分别为HBeAg阳性，而在安慰剂组没有。在拉米夫定组和恩替卡韦组为34.2％，36.0％的患者e抗原转阴，而在第12周安慰剂的病人没有在随访期间HBeAg的转阴。
结论：抗病毒治疗治疗慢性乙型肝炎肝功能衰竭患者的死亡率显着降低。拉米夫定和恩替卡韦都可以作为初始治疗慢性乙型肝炎肝功能衰竭的死亡率降低患者规定。

咬牙硬挺

感谢楼主