本帖最后由 StephenW 于 2011-10-27 14:39 编辑
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.
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