[英语，临床，欧洲肝病学会]192 weeks on Tenofovir

StephenW

HBV Genotype Predicts HBeAg Seroconversion on Tenofovir

SUMMARY: Chronic hepatitis B patients with HBV genotype A and lower  HBsAg levels at baseline were more likely to experience HBeAg seroconversion during treatment with tenofovir (Viread), researchers reported at EASL 2011.
By Liz Highleyman

Effectiveness of treatment for chronic hepatitis B virus (HBV) infection is assessed in various ways, including decreased HBV DNA viral load, normalization of ALT liver enzyme levels, and hepatitis B "e" antigen (HBeAg) and hepatitis B surface antigen (HBsAg) seroconversion  and loss. In a poster presentation at the European Association for the Study of the Liver's International Liver Congress (EASL 2011) this month in Berlin, Jenny Heathcote and colleagues  described a study looking at factors that predict HBeAg seroconversion among people on long-term tenofovir treatment.
The analysis included 259 participants in the pivotal Gilead Study 103 who were HBeAg positive at baseline. About 70% were menand about one-third were Asian. More than half had advanced  fibrosis or cirrhosis. HBV genotypes A, B, C, D were all well  represented.
Participants were randomly assigned to take tenofovir or adefovir (Hepsera) for 48 weeks. After the randomized phase, all patients could take open-label tenofovir and were followed through 192 weeks (about 4 years); the ongoing study will continue through week 384. Based on the study protocol, patients with HBeAg seroconversion  continued on treatment until they achieved either HBsAg loss or seroconversion
Briefly, the main study results showed that 70% of patients treated with  tenofovir through week 192 maintained undetectable HBV DNA, about 80% had normal ALT levels, and they experienced increasing  HBeAg and HBsAg loss over time.

                Results

	Overall,104 patients (40%) experienced at least 1 episode of HBeAg  seroconversion during 192 weeks of treatment:
	72 who stayed on tenofovir the whole time; 32 who switched from adefovir to tenofovir.
	The mean time to the first HBeAg seroconversion was 69 weeks.
	The proportion of patients with HBeAg seroconversion who also  achieved HBsAg loss increased over time.
	People  with all HBV genotypes experienced HBeAg seroconversion, but this was more likely in people with genotype A:
	Genotype D vs A: odds ratio 0.28, or 72% less likely; Genotype C vs A: odds ratio 0.18; Genotype B vs A: odds ratio 0.15.
	In a multivariate analysis, HBV genotype and baseline  HBsAg level were significantly associated with HBeAg seroconversion.
	There were no significant associations, however, between HBeAg seroconversion and other baseline characteristics including race/ethnicity, sex, HBV viral load, ALT level, or Knodell              necroinflammatory score.

"InStudy 103, HBeAg seroconversion was found in all major genotypes,"  the investigators concluded. In a multivariate model of baseline factors, they added, only genotype and lower baseline HBsAg  levels were "significantly predictive" of HBeAg seroconversion.
                  
Investigator affiliations: Patient Clinical Research, Toronto Western Research Institute, Toronto Western Hospital, Toronto, ON, Canada; Department of Gastroenterology, Hepatology and Endocrinology,                   Medical School of Hannover, Hannover, Germany; Service d'Hépato-Gastroentérologie, Hôpital Claude Huriez 2ème Étage Est, Lille, France; Gilead Sciences Inc., Foster City, CA.

4/12/11
Reference
J Heathcote, M Manns, P Mathurin, et al. Baseline genotype and HBsAg were found to have significant association with HBeAg seroconversion following up to 4 years of tenofovir disoproxil fumarate treatment. 46th Annual Meeting of the European Association for the Study of the Liver (EASL 2011). Berlin. March 30-April           3. Abstract 592.

StephenW

乙型肝炎病毒基因型对泰诺福韦e抗原血清转换预测
结论：慢性乙型肝炎患者乙肝病毒基因型A和乙肝表面抗原在基准水平较低更有可能体验到在与泰诺福韦（VIREAD的）治疗HBeAg血清转换，研究人员在欧洲肝病学会2011年。

由Liz Highleyman
治疗的有效性为慢性乙型肝炎病毒（HBV）感染是评估各种方式，包括降低乙肝病毒DNA的病毒载量，肝酶水平的ALT正常化和乙肝的“e”抗原（HBeAg）和乙肝表面抗原（HBsAg）血清和损失。

在一个肝脏的国际肝病会议研究（欧洲肝病学会2011年）本月份在柏林举行的欧洲协会的海报介绍​​，珍妮希思科特和同事描述了一个学习的因素，预测e抗原之间长期看泰诺福韦治疗的血清转换。

分析包括259研究中的关键基列103与会者谁在基线为HBeAg阳性。约70％为男性，约三分之一是亚裔。超过一半有晚期肝纤维化或肝硬化。乙肝病毒基因型甲，乙，丙，丁都是很好的体现。

受试者被随机分配到48周泰诺福韦采取或阿德福韦（Hepsera）。随机阶段后，所有患者可采取开放标签泰诺福韦，并通过一九二个星期（约4岁），其次，这项正在进行的研究将继续通过每周384。在研究方案的基础上，与HBeAg血清转换患者继续治疗，直到他们达到或HBsAg转阴或血清转化

简单来说，主要的研究结果显示，70％的患者通过治疗维持泰诺福韦，HBV DNA转阴，约80％有192周ALT水平正常，而且越来越有经验的HBeAg和HBsAg随着时间的损失。

结果
总体而言，104例（40％）在192周的治疗，至少有1 HBeAg血清转换的插曲：
72谁在替诺福韦的全部时间停留;
32谁从阿德福韦转换到泰诺福韦。
的平均时间第一HBeAg血清转换为69周。
与HBeAg血清转换的患者谁也取得HBsAg转阴的比例增加了时间。
乙肝病毒基因型与所有人民所经历HBeAg血清转换，但这个更符合基因型以人可能会：
  
D型VS的：胜算比0.28，即72％的可能性较小;
C基因型与甲：胜算比0.18;
B型VS的：胜算比0.15。


在多变量分析，乙肝病毒表面抗原基因型和基线水平显着相关的HBeAg血清转换。
没有显着关联，不过，在HBeAg血清转换和其他基线特征包括种族/种族，性别，乙肝病毒载量，ALT水平，或Knodell坏死性炎症评分。

“在研究103，e抗原转阴是在所有主要基因型发现，”研究者的结论。在一个多因素模型的基准，他们补充说，只有基因型和基线HBsAg水平低是“显着预测”的HBeAg血清转换。

调查背景：病人的临床研究，多伦多西方研究所，多伦多西区医院，多伦多，ON，加拿大，胃肠病，肝病及内分泌医学汉诺威，汉诺威，德国学校部;服务德肝，Gastroentérologie，总医院克劳德Huriez 2ème Étage村，里尔，法国公司Gilead Sciences公司，福斯特城，加利福尼亚。

4/12/11

参考

Ĵ希思科特，男曼斯，磷马图林，等。基线基因型和HBsAg中发现有与HBeAg血清转换后长达4年治疗富马酸泰诺福韦disoproxil显着关联。第46届年会的欧洲协会的肝脏（欧洲肝病学会2011年）的研究。柏林。 3月30日至四月三号。摘要592。

lin12345

QQ371427934

HBV genotype and baseline  HBsAg level were significantly associated with HBeAg seroconversion.