AASLD 2011:5 years of Treatment with Tenofovir DF (TDF) forChronic Hepatitis

StephenW

Five years of Treatment with Tenofovir DF (TDF) for Chronic Hepatitis B (CHB) Infection in Asian Patients is Associated with Sustained Viral Suppression and Significant Regression of Histological Fibrosis and Cirrhosis
E. J. Gane1; P. Marcellin2; W. Sievert3; H.N. Trinh4; M. L. Shiffman5; M. Washington6; C.N. Barnes7; J. D. Bornstein7; J. F. Flaherty7;E. Heathcote8
1. Middlemore Hospital,Auckland, New Zealand.
2. Hôpital Beaujon, Clichy, France.
3. Monash University,Melbourne, VIC, Australia.
4. San Jose Gastroenterology, San Jose, CA, United States.
5. Virginia Commonwealth University Medical Center, Richmond, VA, United States.
6. Vanderbilt University,Nashville, TN, United States.
7. Gilead Sciences Inc., Foster City, CA, United  States.
8. University of Toronto,Toronto, ON, Canada.

Background. TDF has demonstrated efficacy and safety inpatients with CHB infection, including Asian patients. Here we present 5 yearon-treatment virologic and paired histologic assessment data in an Asian subsetof patients who are HBeAg negative (Study 102) and HBeAg positive (Study 103).

Methods. After 48 weeks of double-blind comparison of TDF to adefovir dipivoxil, all patients undergoing liver biopsy were eligible to continue open-label TDF. Subjects were assessed every 3 months for safety, virologic efficacy and resistance surveillance. Repeat liver biopsies were performed in both studies at Year 5 and reviewed centrally by an independent blinded pathologist.

Results. 641 patients were initially randomized and treated including 189 (30%)Asian patients. A total of 163/189 (86%) Asian patients completed the randomized phase and entered the TDF extension phase, and at Year 5, 139/163(85%) remained on study. Histologic assessment of liver histology at baseline and Year 5 was available for 72 Asian patients. Baseline characteristics for Asians were similar to non-Asians. At Year 5, the proportion of patients with HBV DNA<400 copies/mL (missing = failure) and ALT normalization (observed) were 74%and 76%, and 83% and 81% for Asian and non-Asian patients, respectively. NoAsian patients had loss of HBsAg. Histologic improvement (≥2 point decrease in Knodell necroinflammatory score and no worsening of fibrosis) occurred at Year5 for 65/72 (90.3%) Asian patients. Overall, 42/72 (58.3%) Asian patients had histologic regression of fibrosis (≥1 point decrease in Ishak score) at Year 5,including 16/18 (88.9%) patients with cirrhosis at baseline who had histologic regression (Ishak <5), while 28/72 (38.9%) showed no change in fibrosis. TDF was well tolerated over the 5 year period; <2% of Asian patients discontinued TDF for an adverse event (AE), and Grade 2 - 4 AEs were comparable in Asians compared to the overall study population. Through Year 5, <1.2% of Asian patients experienced a confirmed increase of ≥0.5 mg/dL in SCr, decease in serum PO4 <2.0 mg/dL, or decrease in CrCL <50 mL/min. There were no patients with resistance detected to TDF through Year 5.

Conclusions. In a subset of Asian patients, TDF remains safe and effective over a 5 year treatment period. Most patients (90%) showed overall histologic improvement; additionally, 89% of Asian patients with cirrhosis at entry have regression of histologic cirrhosis at 5 years. These data are consistent with those of the overall study population, and also support the link between long term HBV suppression with TDF and regression of fibrosis in the majority of treated patients.

StephenW

治疗慢性乙型肝炎（CHB）感染在亚洲患者替诺福韦DF（TDF）的五年是与持续的病毒抑制和组织学纤维化和肝硬化的重大回归
EJ Gane1; P. Marcellin 2; W。Sievert为3; HN Trinh4; ML Shiffman5; M.华盛顿6; CN Barnes7; JD Bornstein7，摩根富林明Flaherty7; E.希思科特8
1。 Middlemore医院，新西兰的奥克兰。
2。医院的Beaujon，克利希，法国。
3。莫纳什大学，墨尔本，维多利亚州，澳大利亚。
4。圣何塞消化科，圣何塞，加利福尼亚，美国。
5。弗吉尼亚州里士满，弗吉尼亚联邦大学医学中心，美国。
6。范德比尔特大学，美国田纳西州纳什维尔。
7。 Gilead Sciences公司，福斯特城，加利福尼亚，美国。
8。 ON，加拿大，多伦多，多伦多大学。
  
背景。 TDF已经证明在慢性乙型肝炎病毒感染的患者，其中包括亚洲患者的疗效和安全性。在这里，我们目前的5年治疗病毒学和配对在亚洲的一个子集谁是病人HBeAg阴性（102研究）和HBeAg阳性（103研究）的组织学评估数据。
的方法。双盲比较TDF阿德福韦48周后，所有患者接受肝活检资格继续开放标签TDF。受试者的安全性评估，每3个月，病毒学疗效和耐药性监测。重复肝活检进行了5年，在这两项研究由一个独立的盲病理学家集中审查。
结果。 641例患者最初的随机和治疗，其中189（30％）亚洲患者。共一百八十九分之一百六十三（86％）亚洲患者的随机阶段的完成和进入TDF推广阶段，并在5年，一百六十三分之一百三十九（85％）仍然在研究。肝脏组织学的组织学评估在基线和5年72例亚洲。适合亚洲人的基线特征相似的非亚洲人。在5年中，HBV DNA的患者比例<400拷贝/毫升（失踪=失败）和ALT正常化（观察），分别为74％和76％，83％和81％为亚洲和非亚洲患者。没有一个亚洲患者HBsAg消失。组织学改善（≥2点减少Knodell坏死性炎症评分和纤维化没有恶化）发生在5年七十二分之六十五（90.3％）亚洲患者。总体而言，亚洲患者42/72（58.3％）在5年病理纤维化（≥1点伊沙克得分下降）回归，包括16/18（88.9％）患者在基线肝硬化病理回归（伊沙克<5 ），而七十二分之二十八（38.9％）没有表现出纤维化的改变。 TDF耐受性良好，5年期以上的; <2％，亚洲患者的不良事件（AE）停止TDF，等级2 - 4个AES相比，整体研究人口在亚洲人比较。通过5年，亚洲患者<1.2％经历了证实增加≥0.5毫克/ SCR，去世DL血清磷酸盐<2.0毫克/升，或在肌酐清除率下降<50毫升/分钟。有阻力通过5年未检测到TDF的患者。
结论。在亚洲患者的一个子集，华盈仍然超过5年的治疗期间的安全和有效。大多数患者（90％），显示整体组织学改善;此外，亚洲肝硬化患者在入境的89％在5年组织学肝硬化的回归。这些数据的整体研究人口相一致，并且还支持之间长期HBV抑制纤维化治疗的患者多数与TDF和回归的链接。

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亚裔乙肝患者五年替诺治疗情况：持续病毒抑制+显著纤维化、肝硬化逆转

背景：替诺已经体现出在乙肝治疗上的有效性和安全性（包括亚裔患者）。我们在此展示5年的病毒学、历史治疗数据评估，数据包括HBeAg 阴性（102）和HBeAg 阳性（103）亚裔患者分组。

方法：48周替诺、阿德双盲实验，所有经过肝穿检查患者符合进行替诺治疗标准。为了获得安全性、抗病毒效果和耐药监测情况，患者每3个月检查1次。第5年再次进行肝穿检查，由独立病理学家集中执行。

结果：641患者参加双盲试验，其中189 (30%)亚裔患者。163/189 (86%)亚裔患者完成随机阶段进入明确使用替诺阶段，第5年时，剩余139/163(85%) 。第5年时具有肝组织学评估数据的亚裔患者剩余72人。亚裔与非亚裔患者基值相近。第5年，HBV DNA<400 copies/mL（退出算作dna未转阴）亚裔患者比例为74%，ALT正常亚裔患者比例76%，对应的非亚裔患者比率83%和81%。非亚裔患者有HBsAg转阴的。第5年时发现组织学改善的亚裔患者比例为65/72 (90.3%)。

总之，第5年时，42/72 (58.3%)亚裔患者有纤维化组织学改善，包括16/18 (88.9%)有肝硬化组织学改善，并且 28/72 (38.9%) 纤维化无改善。替诺5年耐受率良好；<2%亚裔患者因病情恶化退出替诺实验，（以下可能是纤维化改善指标）Grade 2 - 4 AEs were comparable in Asians compared to the overall study population. Through Year 5, <1.2% of Asian patients experienced a confirmed increase of ≥0.5 mg/dL in SCr, decease in serum PO4 <2.0 mg/dL, or decrease in CrCL <50 mL/min. 5年没有患者替诺耐药。

结论。亚裔患者中，替诺使用5年具有安全性和有效性。大部分患者(90%) 有总体组织学改善；并且，89%亚裔肝硬化患者5年后有组织学改善。这些数据与所有患者样本结论一致，即使用替诺能获得乙肝病毒长期抑制和大多数患者纤维化逆转效果。

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回复 StephenW 的帖子

第5年，HBV DNA<400 copies/mL（退出算作dna未转阴）和ALT正常比例达到74%和76%，亚裔患者83%，非亚裔患者81%（ At Year 5, the proportion of patients with HBV DNA<400 copies/mL (missing = failure) and ALT normalization (observed) were 74%and 76%, and 83% and 81% for Asian and non-Asian patients, respectively. ）。

问下，“亚裔患者83%，非亚裔患者81%”这个指什么比例？没看出来

StephenW

把握当下 发表于 2011-10-27 22:56
回复 StephenW 的帖子

第5年，HBV DNA

"At Year 5, the proportion of patients with HBV DNA<400 copies/mL (missing = failure) and ALT normalization (observed) were 74%and 76%, and 83% and 81% for Asian and non-Asian patients, respectively. ）。"  means (I think):

At year 5 -       Asian -  74% has HBVDNA < 400 copies/mL (missing = failure)
                                 76% has ALT normalization(observed)

At year 5 - non-Asian - 83% has HBVDNA < 400 copies/mL (missing = failure)
                                 81% has ALT normalization(observed)

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StephenW 发表于 2011-10-28 03:30
"At Year 5, the proportion of patients with HBV DNA

谢谢，我看的时候没动脑子

interdetect

StephenW 发表于 2011-10-27 14:29
Five years of Treatment with Tenofovir DF (TDF) for Chronic Hepatitis B (CHB) Infection in Asian Pat ...

Can you get the full text?

StephenW

interdetect 发表于 2011-10-28 09:28
Can you get the full text?

Don't know. Not at the moment, all papers, abstract, and posters are under embargo.