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.
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。
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 ...
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