标题: AASLD 2011:Response to peginterferon alfa-2a in HBeAg-negative CHB: baseline and [打印本页] 作者: StephenW 时间: 2011-10-24 22:22 标题: AASLD 2011:Response to peginterferon alfa-2a in HBeAg-negative CHB: baseline and
本帖最后由 StephenW 于 2011-10-24 22:23 编辑
Response to peginterferon alfa-2a in HBeAg-negative CHB: baseline and on-treatment kinetics of HBsAg serum levels vary according to HBV genotype
M. R. Brunetto1; P. Marcellin2; B. Cherubini1; C. Yurdaydin3; P. Farci4; S. J. Hadziyannis5; V. Rothe6; L. Regep7; H. Kapprell8; F. Bonino1
1. General Medicine 2 - Digestive and Liver Disease, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.
2. Service d’Hepatologie and Centre de Recherches Biologiques Beaujon , University of Paris, Clichy, France.
3. Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey.
4. Department of Medical Sciences, University of Cagliari, Cagliari, Italy.
5. Department of Medicine and Hepatology, Henry Dunant Hospital, Athens, Greece.
6. IST GmbH, Mannheim, Germany.
7. F. Hoffmann-La Roche, Basel, Switzerland.
8. ABBOTT GmbH & CO KG, Wiesbaden, Germany.
HBsAg levels during peginterferon alfa-2a (PEG-IFNα-2a) therapy are associated with post-treatment response; different HBsAg kinetic patterns were observed. The influence of HBV genotype on on-treatment HBsAg kinetics and end of treatment levels in patients with 5 yrs post-treatment follow-up was assessed. Methods: HBeAg-negative patients who had received PEG-IFNα-2a±lamivudine in the phase 3 study, followed up for 5 yrs post-treatment and with available HBsAg data were analyzed. HBsAg kinetics in responders (HBV DNA<2000 IU/mL 5 yrs post-treatment) and nonresponders (NR, HBV DNA>2000 IU/mL 5 yrs post-treatment) and by genotype are described (patients with HBsAg at baseline and wks 12, 24 and 48). ROC analysis determined HBsAg levels associated with sustained response, NR or relapse (HBV DNA<2000 IU/mL at wk 48, >2000 IU/mL 5 yrs post-treatment) in patients with HBsAg levels at baseline and wk 48 (genotype A: n=13; B: n=64; C: n=91; D: n=31).Results: Baseline HBsAg levels were highest in genotype A (15002 vs 4138, 2648 and 5910 IU/mL for genotypes B, C and D; P<0.0001 for the global comparison). The greatest difference in HBsAg kinetics between responders and NR was at wks 12–24 in genotype A and wks 0–12 in genotypes B and D (table). The difference was minimal in genotype C. In genotypes A and B the difference resulted from the HBsAg decline in responders while the difference in genotype D resulted from the HBsAg increase in NR. As the patterns of on-treatment HBsAg decline varied between genotypes it was not possible to find a single on-treatment predictive rule at a single time point. Applying genotype-specific cut-offs at week 48 gave high positive predictive values (PPV). In genotype A, 100% (3/3) of responders had HBsAg≤400 IU/mL vs 10% (1/10) of NR/relapsers. In genotype B, 100% (7/7) of responders had HBsAg≤50 IU/mL vs 14% (8/57) of NR/relapsers. In genotype C, 41% (11/27) of responders had HBsAg≤50 IU/mL vs 6% (4/64) of NR/relapsers. In genotype D, 60% (6/10) of responders had HBsAg≤1000 IU/mL vs 9.5% (2/21) of NR/relapsers. Conclusion: As on-treatment HBsAg kinetics vary between genotypes, it is not possible to identify a single threshold associated with high PPVs in all genotypes. On the contrary, genotype-specific thresholds should be considered as they are associated with high PPVs.