[AASLD 2012]恩替卡韦治疗超过5年的治疗

肝胆速递

CONTROL ID: 1418022
PRESENTATION TYPE: Oral or Poster
CURRENT CATEGORY: Hepatitis B
CURRENT DESCRIPTORS: I02. Treatment and Clinical Trials
TITLE: Entecavir treatment for NUC naïve, field practice patients with chronic hepatitis B: excellent viral suppression and safety profile over 5 years of treatment
AUTHORS (FIRST NAME, LAST NAME): Pietro Lampertico1, Roberta Soffredini1, Mauro Viganò2, Eliseo Minola3, Giuliana Cologni4, Marco Rizzi4, Serena Zaltron5, Andrea Vavassori5, Giampiero Carosi5, Elena Angeli6, Guido A. Gubertini6, Carlo F. Magni6, Giuliano Rizzardini6, Angela Testa7, Gianpiero D'Offizi7, Maria Vinci8, Giovambattista Pinzello8, Erika Fatta9, Silvia Fargion9, Silvia Colombo10, Osvaldo Fracassetti10, Paolo Del Poggio11, Barbara Coco12, Maurizia R. Brunetto12, Marco Andreoletti13, Agostino Colli13, Massimo Fasano15, Teresa A. Santantonio14, Guido Colloredo16, Luisa Pasulo17, Stefano Fagiuoli17, Alberto Eraldo Colombo18, Giorgio A. Bellati18, Maria Milanese19, Natalia M. Terreni20, Michela Quagliuolo21, Giovanna Lunghi22, Floriana Facchetti1, Federica Invernizzi1, Massimo Colombo1
Institutional Author(s):
INSTITUTIONS (ALL): 1. 1st Division of Gastroenterology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università di Milano, Milan, Italy.
2. U.O.Epatologia, Ospedale San Giuseppe, Università degli Studi di Milano, Milan, Italy.
3. Servizio Malattie Epatiche e Infettive, Humanitas Gavazzeni, Bergamo, Italy.
4. Infectious Diseases, Ospedali Riuniti di Bergamo, Bergamo, Italy.
5. II Divisione Malattie Infettive, Azienda Ospedaliera Spedali Civili, Brescia, Italy.
6. I and II Division Infectious Diseases, Ospedale Luigi Sacco, Milan, Italy.
7. INMI, IRCCS L. Spallanzani, Roma, Italy.
8. SC Epatologia e Gastroenterologia, Ospedale Niguarda Cà Granda, Milan, Italy.
9. Internal Medicine 1b, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
10. U.O. Epatologia, Ospedale di Treviglio, Treviglio, Italy.
11. U.O. Gastroenterologia, Policlinico S. Marco, Zingonia, Italy.
12. U.O. Epatologia, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
13. S.C. Medicina Generale, Ospedale A. Manzoni, Lecco, Italy.
14. Clinic of Infectious Diseases, Università di Foggia, Foggia, Italy.
15. Clinic of Infectious Diseases, Università di Bari, Bari, Italy.
16. Division of Medicine, Policlinico San Pietro, Ponte San Pietro, Italy.
17. Gastroenterology Unit, Liver and Lung Transplantation Center, Ospedali Riuniti di Bergamo, Bergamo, Italy.
18. Unità Operativa di Medicina, Servizio di Epatologia, Ospedale Sant'Anna, Como, Italy.
19. Liver Center, Clinica Medica, Ospedaliera San Gerardo, Università Milano Bicocca, Monza, Italy.
20. U.O. Gastroenterologia, Ospedale Valduce , Como, Italy.
21. U.O. Gastroenterologia, Azienda Ospedaliera di Melegnano, Melegnano, Italy.
22. Istituto di Medicina Preventiva, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
ABSTRACT BODY:
Background and aim:
Aim of the study was to assess the long term effectiveness and safety of Entecavir (ETV) monotherapy in NUC-naïve patients.
Methods: 418 consecutive NUC-naïve patients with CHB were recruited in 21 Liver Units in Italy and treated with ETV 0.5 mg for 52 months (2-66). At baseline, age was 58 years, 76% males, 83% HBeAg-negative, HBV DNA 6.0 log IU/ml, 85% with elevated ALT, 49% cirrhotics, 56% with concomitant diseases/medications. Liver function tests and HBV DNA, were assessed by a sensitive assays every 3 months. Virological breakthrough was defined as > 1 log 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 increased over time reaching 100% in both HBeAg positive and negative patients at year 5. A primary non response occurred in 1%, a partial response at week 48 in 12%, a blip of viremia in 11%, a virological breakthrough in 4% and drug resistance in <1% of the patients (one case at year 3). HBeAg seroconversion and HBsAg loss rates progressively increased up to 60% and 25% at year 5, respectively, with 12 patients withdrawing successfully from therapy. ALT levels became normal in 90% of patients. Among 164 cirrhotics, clinical decompensation did not occurr but HCC developed at an yearly rate of 2.5%, despite viral replication was fully suppressed in most cases. No safety issues were reported.
Serum creatinine remained unchanged during treatment [from 0.90 (0.60-9.0) at baseline vs 0.90 (0.5-2.0) mg/dl] as well as the proportion of patients with serum creatinine > 1.5 mg/dl (2% at baseline and during the study). Blood phosphorus levels also remained unchanged [from 3.4 (2.4-4.3) to 3.1 (2.4-4.2) mg/dl] with < 1% of the patients with low phosphorus levels or significant proteinuria. TmPO4/GFR ratio, a marker of urinary phosphate reabsorption, was <0.70 mmol/L in ~20% at month 12 and throughout the study.
Overall, 7% of the patients died, 3% were transplanted, 7% required treatment adaptation (PEG or ETV+TDF), 3% stopped ETV following HBsAg clearance and 9% were lost to follow-up. Conclusion. Long-term entecavir monotherapy efficiently suppressed HBV replication in naïve field practice patients with CHB but it failed to prevent hepatocellular carcinoma in cirrhotics.

肝胆速递

控制ID：1418022
外观类型：口头报告或墙报
当前类别：B型肝炎
描述符：I02。治疗与临床试验
标题：国统会天真，现场实践与慢性B型肝炎患者：恩替卡韦治疗超过5年的治疗，良好的抑制病毒和安全性
香港（姓氏，名字）：彼得Lampertico1，罗伯塔Soffredini1，毛罗Viganò2，Minola3伊利索，朱利安娜Cologni4，马可Rizzi4，小威Zaltron5，安德烈Vavassori5，詹皮耶罗·Carosi5，埃琳娜Angeli6，吉A. Gubertini6，卡罗F. Magni6，朱利亚诺。 Rizzardini6，安吉拉Testa7次，Gianpiero D'Offizi7，，，玛丽亚Vinci8，Giovambattista Pinzello8，埃里卡Fatta9，西尔维娅Fargion9，保罗·德尔Poggio11 Fracassetti10，西尔维娅Colombo10，奥斯瓦尔多，芭芭拉Coco12，Maurizia R. Brunetto12，马可Andreoletti13，阿戈斯蒂诺Colli13，马西莫Fasano15，邓丽君A. Santantonio14，圭多Colloredo16次，路易莎Pasulo17，斯特凡诺Fagiuoli17次，乔治A.阿尔贝托Eraldo Colombo18，Bellati18，玛丽亚纳塔利娅M. Terreni20，Michela旅游Quagliuolo21，乔凡娜Lunghi22，弗洛里亚纳Facchetti1，Milanese19，费德里卡Invernizzi1，马西莫Colombo1
机构（S）：
机构（ALL）：1。 1胃肠科，中基金会IRCCS CA的的格兰达Ospedale Maggiore Policlinico，米兰，意大利米兰大学留学。
2。 UOEpatologia，Ospedale圣朱塞佩如Università教堂，米兰，意大利米兰STUDI。
3。 ËInfettive SERVIZIO Malattie Epatiche，胡马尼塔斯加瓦泽尼，贝加莫，意大利。
4。感染性疾病，二贝加莫，贝加莫，意大利Ospedali，里尤尼蒂工厂。
5。 II Divisione Malattie Infettive，AZIENDA Ospedaliera Spedali文明的，布雷西亚，意大利。
6。我和II组感染性疾病，Ospedale，米兰，意大利的路易吉·萨科。
7。英迈，，意大利罗马IRCCS L.斯帕兰扎尼的。
8。 SC EpatologiaËGastroenterologiaCà格兰达，Ospedale酒店距离Niguarda，米兰，意大利。
9。内科1B中基金会IRCCS CA格兰达Ospedale马焦雷Policlinico大学留学教堂，米兰，意大利米兰STUDI。
10。 U.O. Epatologia，Ospedale Treviglio，二Treviglio，意大利。
11。 U.O. Gastroenterologia，马可，Zingonia，意大利Policlinico S.。
12。 U.O. Epatologia，AZIENDA Ospedaliero Universitaria蜗牛，意大利比萨。
13。的SC MEDICINA兴业，莱科，意大利，Ospedale A.曼佐尼。
14。诊所的传染病如Università二福贾，福贾，意大利。
15。诊所的传染病如Università二巴里，巴里，意大利。
16。医学部，Policlinico浦圣彼得，圣彼得大教堂，意大利。
17。胃肠病学组，肝，肺移植中心，Ospedali，里尤尼蒂工厂二贝加莫，贝加莫，意大利。
18。安盟Operativa二MEDICINA，SERVIZIO二Epatologia，Ospedale圣安娜，科莫，意大利。
19。肝病中心，CLINICA的药物，Ospedaliera新赫拉尔多意大利，蒙扎，米兰比可卡大学留学。
20。 U.O. Gastroenterologia，Ospedale Valduce，意大利科莫。
21。 U.O. Gastroenterologia，AZIENDA Ospedaliera二梅莱尼亚诺，梅莱尼亚诺，意大利。
22。 ISTITUTO的二MEDICINA Preventiva中基金会IRCCS CA格兰达Ospedale马焦雷Policlinico大学留学教堂，米兰，意大利米兰STUDI。
抽象的身体：背景和目的：这项研究的目的是评估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性。方法：418连续NUC-天真的慢性乙型肝炎患者在意大利聘请21肝的单位和恩替卡韦0.5 mg，为期52个月（2-66）处理。在基线时，年龄为58​​岁，76％为男性，83％HBeAg阴性，HBV DNA 6.0日志IU / ml时，85％ALT升高，49％的肝硬化患者，有56％伴发疾病/药物。肝功能检查和HBV DNA，一个灵敏的检测方法，每3个​​月进行了评估。病毒学突破被定义为> 1日志ü增加的病毒血症，一个是“昙花一现”检测到的病毒血症（<100 IU / ml）的在病毒学应答器的发生。结果。 HBV DNA检测不到率逐步增加在这两个HBeAg阳性和阴性的患者在5年的时间达到100％。的主要反应发生在1％，部分反应在48周中有12％，昙花一现的病毒血症，11％，4％和耐药，病毒学突破在<1％的患者（1例在第3年） 。 HBeAg血清转换和HBsAg转阴率逐步提高到60％和25％的5年中，分别有12例患者，从治疗成功退出。 90％的患者ALT水平恢复正常。 164肝硬化患者中，临床失代偿没有occurr，但，HCC在每年2.5％的速度发展，但在大多数情况下，被完全抑制病毒的复制。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（0.60-9.0）在基线和0.90毫克/分升（0.5〜2.0）]，以及比例的患者血清肌酐> 1.5毫克/分升（基础值的2％，并在学习）。血液中磷的含量也保持不变[] <1％的患者低磷水平或重大蛋白尿从3.4（2.4-4.3）3.1（2.4-4.2）毫克/分升。 TmPO4/GFR比，一个标记的尿中磷的重吸收，是<0.70 mmol / L的〜20％在12个月，并在整个研究。
总体而言，7％的患者死亡，3％的移植，3％，7％需要治疗的适应（PEG或ETV + TDF的）停止ETV HBsAg清除和9％，分别输给了后续。结论。长期恩替卡韦单药治疗能有效地抑制HBV复制的慢性乙型肝炎患者在天真的现场实践，但未能阻止肝硬化患者肝癌.

肝胆速递

请注意：
1.研究在意大利.基因型分布没有说明.
2.非常高的基线58岁（平均，中位数(median)？)

咬牙硬挺

肝癌和肝硬化的关联度很高。所以及早抗病毒防止硬化