CONTROL ID: 1414997 | ||||||||||||||||||||||||
PRESENTATION TYPE: Oral or Poster | ||||||||||||||||||||||||
CURRENT CATEGORY: Hepatitis B | ||||||||||||||||||||||||
CURRENT DESCRIPTORS: I02. Treatment and Clinical Trials | ||||||||||||||||||||||||
TITLE: New treatment strategy: switching from long-term entecavir to peginterferon alfa-2a induces HBeAg seroconversion/HBsAg clearance in patients with HBeAg-positive chronic hepatitis B | ||||||||||||||||||||||||
AUTHORS (FIRST NAME, LAST NAME): Qin Ning1, Meifang Han1, Yongtao Sun2, Jia-ji Jiang3, Deming Tan4, Jinlin Hou5, Hong Tang6, Jifang Sheng7, Mianzhi Zhao8 | ||||||||||||||||||||||||
Institutional Author(s): Ning | ||||||||||||||||||||||||
INSTITUTIONS (ALL): 1. Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 2. Tangdu Hospital, the Fourth Military Medical University, Xi'an, China. 3. The First Hospital, Fujian Medical University, Fuzhou, China. 4. Xiangya Hospital, Central South University, Changsha, China. 5. Nanfang Hospital, Nanfang Medical University, Guangzhou, China. 6. West China Hospital, Sichuan University, Chengdu, China. 7. The First hospital, Zhejiang University, Hangzhou, China. 8. Shanghai Roche Pharmaceutical Co., Ltd, Shanghai , China. | ||||||||||||||||||||||||
ABSTRACT BODY: Study purpose: Nucleos(t)ide analog therapy in chronic hepatitis B patients can result in maintained HBV DNA suppression, but most patients (>50%) do not achieve a durable off-treatment response and therefore potentially require life-long therapy. The study objective was to determine whether patients with maintained HBV DNA suppression on entecavir (ETV) can achieve HBeAg seroconversion/HBsAg clearance by switching to peginterferon alfa-2a (Peg-IFNα-2a). Methods: This was a multicenter, randomized, open-label study in HBeAg(+) patients. Patients receiving ETV (0.5 mg QD) for 9–36 months, with HBV DNA <103 copies/mL + HBeAg <100 PEIU/mL, either switched to Peg-IFNα-2a (180 µg for 48 weeks) or continued ETV for a further 48 weeks. There was an 8-week overlap in the Peg-IFNα-2a arm. The primary endpoint was HBeAg seroconversion at end of treatment (week 48). Secondary endpoints included HBsAg clearance and HBV DNA <1000 copies/mL. Adverse events (AEs) were recorded. Results: The mean age was 33 years in both arms. Mean HBV DNA, ALT, HBeAg and HBsAg levels at baseline were low and similar between arms. Mean duration of ETV treatment prior to switching to Peg-IFNα-2a was comparable between arms (20 months). HBeAg seroconversion and HBsAg clearance rates at week 48 were significantly higher with Peg-IFNα-2a than with ETV (table). HBeAg loss + HBsAg <3000 IU/mL at baseline resulted in 19% of patients achieving HBsAg clearance. On-treatment HBsAg decline from baseline to week 48 was significantly greater with Peg-IFNα-2a than ETV (–0.81 vs –0.06 log10 IU/mL; p<0.05). Some patients relapsed (HBV DNA ≥1000 copies/mL) when switched to Peg-IFNα-2a (23 patients, 24%), but median ALT levels were similar or lower in patients with relapse than those without. AEs and serious AEs were higher with Peg-IFNα-2a than ETV (AEs 69% vs 5%; serious AEs 6% vs 0%), but only 7% of Peg-IFNα-2a-treated patients discontinued therapy. AEs in patients switched to Peg-IFNα-2a were similar to treatment-naïve patients from previous studies. Conclusion: Patients with maintained virologic response on ETV who switch to a finite course of Peg-IFNα-2a achieve significantly higher rates of HBeAg seroconversion/HBsAg clearance than continuing on ETV. HBeAg loss + HBsAg <3000 IU/mL at baseline resulted in a high rate of HBsAg clearance (19%). | ||||||||||||||||||||||||
| ||||||||||||||||||||||||
(No Image Selected) | ||||||||||||||||||||||||
Co-Author Disclosure Status | ||||||||||||||||||||||||
The following authors have completed their AASLD 2012 disclosure: | ||||||||||||||||||||||||
Qin Ning: Disclosure completed | ||||||||||||||||||||||||
Meifang Han: Disclosure completed | ||||||||||||||||||||||||
Yongtao Sun: Disclosure completed | ||||||||||||||||||||||||
Jia-ji Jiang: Disclosure completed | ||||||||||||||||||||||||
Deming Tan: No Answer. | ||||||||||||||||||||||||
Jinlin Hou: Disclosure completed | ||||||||||||||||||||||||
Hong Tang: Disclosure completed | ||||||||||||||||||||||||
Jifang Sheng: No Answer. | ||||||||||||||||||||||||
Mianzhi Zhao: Disclosure completed |
[/table][table] |
CONTROL ID: 1421510 |
PRESENTATION TYPE: Oral or Poster |
CURRENT CATEGORY: Hepatitis B |
CURRENT DESCRIPTORS: I02. Treatment and Clinical Trials |
TITLE: Adding peginterferon alfa-2a to entecavir increases HBsAg decline and HBeAg clearance - first results from a global randomized trial (ARES study) |
AUTHORS (FIRST NAME, LAST NAME): Milan J. Sonneveld1, Qing Xie2, Ning-Ping Zhang3, Qin Zhang4, Fehmi Tabak5, Adrian Streinu-cercel6, Jiyao Wang3, Ramazan Idilman7, Annikki de Niet8, Mircea. Diculescu9, Anneke J. van Vuuren1, Elke Verhey1, Bettina E. Hansen1, 10, Harry L. Janssen1 |
Institutional Author(s): |
INSTITUTIONS (ALL): 1. Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands. 2. Infectious Diseases, Ruijin Hospital, Jiaotong University, Shanghai, China. 3. Gastroenterology and Hepatology, Zhong Shan Hospital, Fu Dan University, Shanghai, China. 4. Gastroenterology and Hepatology, Shanghai Public Health Center, Fu Dan University, Shanghai, China. 5. Infectious Diseases, Cerrahpasa Medical School, Istanbul, Turkey. 6. National Institute of Infectious Disease, Bucharest, Romania. 7. Gastroenterology and Hepatology, University of Ankara, Ankara, Turkey. 8. Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, Netherlands. 9. Gastroenterology, Fundeni Cinical Institute, Bucharest, Romania. 10. Public Health, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands. |
ABSTRACT BODY: Background. Entecavir (ETV) is a potent inhibitor of viral replication in HBeAg-positive chronic hepatitis B (CHB) patients, but serological response is infrequently achieved and indefinite therapy should therefore be anticipated in the majority of patients. Addition of peginterferon (PEG-IFN) to ETV may increase serological response rates. Methods. In this investigator-initiated randomized controlled trial 184 HBeAg-positive patients with compensated liver disease were enrolled at 15 sites in Europe and China and allocated to either ETV 0.5mg daily alone for 48 weeks or a 24 week addition of PEG-IFN alfa-2a 180 ug weekly after 24 weeks of ETV monotherapy. Response (HBeAg loss with HBV DNA <200 IU/mL) was assessed at week 48, and responders were allowed to discontinue treatment after 24 weeks consolidation treatment (week 72), with subsequent off-treatment follow-up until week 96. Results at week 48 are presented here. Results. 177 patients received at least one dose of allocated treatment, 93 ETV alone and 84 ETV with PEG-IFN add-on. Sixty-one percent of patients were of Asian ethnicity and all major HBV genotypes were present (A/B/C/D in 7/19/42/32%). A total of 160 patients had reached week 48 by June 2012, and the remaining patients will do so within 2 months. Patients were comparable with regard to important baseline characteristics, except for HBsAg which was higher in patients receiving combination therapy (4.28 versus 4.03 log IU/mL, p=0.05). Response, as well as HBeAg loss alone, was achieved in 18% of patients who received PEG-IFN add-on, compared to 8% of patients treated with ETV alone (p=0.07). PEG-IFN add-on resulted in more decline of HBV DNA (6.33 versus 5.91 log IU/mL, p=0.05), HBeAg (1.99 versus 1.56 log IU/mL, p=0.01) and HBsAg (0.84 versus 0.32 log IU/mL, p<0.001) at week 48. Only one patient (who received PEG-IFN add-on) had clearance of HBsAg at week 48. After adjustment for the differences in baseline HBsAg levels, addition of PEG-IFN was independently associated with response at week 48 (adjusted odds ratio: 3.63, 95% CI: 1.24 – 10.7, p=0.01). Add-on PEG-IFN was well-tolerated and no relevant safety concerns were raised. Conclusion. A 24 week add-on of PEG-IFN treatment increases HBsAg decline and clearance of HBeAg and may therefore improve the chances of finite treatment in HBeAg-positive CHB patients treated with ETV. |
(No Table Selected) |
(No Image Selected) |
Co-Author Disclosure Status |
The following authors have completed their AASLD 2012 disclosure: |
Milan Sonneveld: Disclosure completed |
Qing Xie: Disclosure completed |
Ning-Ping Zhang: Disclosure completed |
Qin Zhang: Disclosure completed |
Fehmi Tabak: Disclosure completed |
Adrian Streinu-cercel: Disclosure completed |
Jiyao Wang: Disclosure completed |
Ramazan Idilman: Disclosure completed |
Annikki de Niet: Disclosure completed |
Mircea. Diculescu: Disclosure completed |
Anneke van Vuuren: Disclosure completed |
Elke Verhey: Disclosure completed |
Bettina Hansen: Disclosure completed |
Harry Janssen: Disclosure completed |
[tr][td] |
CONTROL ID: 1422397 |
PRESENTATION TYPE: Oral or Poster |
CURRENT CATEGORY: Hepatitis B |
CURRENT DESCRIPTORS: I02. Treatment and Clinical Trials |
TITLE: Peginterferon Reduces Intrahepatic HBsAg and is Associated with Histologic Response in Chronic Hepatitis B |
AUTHORS (FIRST NAME, LAST NAME): Pauline Arends1, Vincent Rijckborst1, Milan J. Sonneveld1, Bettina E. Hansen1, 2, Harry L. Janssen1 |
Institutional Author(s): |
INSTITUTIONS (ALL): 1. Dept. of Gastroenterology & Hepatology, Erasmus MC, Rotterdam, Netherlands. 2. Dept. of Public Health, Erasmus MC, Rotterdam, Netherlands. |
ABSTRACT BODY: Background. To date, there is limited knowledge regarding the effect of peginterferon (PEG-IFN) on the expression of intrahepatic hepatitis B virus surface antigen (HBsAg) in chronic hepatitis B (CHB), and how it correlates with serum HBsAg and histological response in the terms of necroinflammation and fibrosis scores. Methods. Fifty-two HBeAg positive CHB patients with paired liver biopsies taken at baseline and after 52 weeks of PEG-IFN therapy and 67 HBeAg negative CHB patients with paired liver biopsies taken at baseline and 24 weeks after 48 weeks of PEG-IFN therapy were studied. Necroinflammation and fibrosis were scored according to the Ishak scoring system. The degree of intrahepatic HBsAg expression was ranked on a scale of 0 to 5. Results. Mean necroinflammatory score at baseline was 5.5 (± 2.2) and did not differ between HBeAg positive and -negative patients. Mean fibrosis score was 2.2 (± 1.4) and was comparable for HBeAg positive and -negative patients. Baseline degree of intrahepatic HBsAg did not differ between HBeAg positive and –negative patients and was not associated with necroinflammatory or fibrosis scores, nor with serum HBsAg. After PEG-IFN the degree of intrahepatic HBsAg significantly reduced in HBeAg negative patients (p<0.001), and a trend was seen in HBeAg positive patients (p=0.088). Patients with a decline in intrahepatic HBsAg had significantly more serum HBsAg decline at the end of follow-up (0.9 vs. 0.4IU/mL, p=0.031). A reduction in necroinflammation (decrease ≥ 2 points) after PEG-IFN treatment was observed in 47% of HBeAg positive patients (P=0.002 compared with baseline) and in 52% of HBeAg negative patients (p<0.001 compared with baseline). Decline in intrahepatic HBsAg and a decrease in necroinflammation appeared to be associated (Spearman’s ρ0.159, p=0.096). Improvement of fibrosis (decrease ≥ 1 point) after PEG-IFN therapy was found in 21% of HBeAg positive and 30% of HBeAg negative patients. However, a significant change in fibrosis score was only observed in HBeAg positive patients (p=0.050). There tended to be a correlation between a decline in intrahepatic HBsAg and fibrosis (Spearman’s ρ0.174, p=0.070). Conclusion. PEG-IFN reduces expression of intrahepatic HBsAg as well as necroinflammation in both HBeAg positive and negative CHB. Decline in fibrosis was only found in HBeAg positive patients. Decline of HBsAg expression in hepatocytes after PEG-IFN was associated with a decline in serum HBsAg and showed a trend toward significance with decline in necroinflammation and fibrosis scores. |
(No Table Selected) |
(No Image Selected) |
Co-Author Disclosure Status |
The following authors have completed their AASLD 2012 disclosure: |
Pauline Arends: Disclosure completed |
Vincent Rijckborst: Disclosure completed |
Milan Sonneveld: Disclosure completed |
Bettina Hansen: Disclosure completed |
Harry Janssen: Disclosure completed |
[/table][table] |
欢迎光临 肝胆相照论坛 (http://hbvhbv.info/forum/) | Powered by Discuz! X1.5 |