Di Wu1, Peng Wang1, Meifang Han1, Yongping Chen2, Xinyue Chen3, Qi Xia4, Weiming Yan1, Xiaoyang Wan1, Chuanlong Zhu5, Qing Xie6, Jiaji Jiang7, Lai Wei8, Deming Tan9, Xiaoguang Dou10, Yanyan Yu11, Jinlin Hou12, Xiaoping Luo13, Qin Ning14. 1. Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095, Jiefang Avenue, Wuhan, 430030, China. 2. Department of Infectious Disease, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. 3. International Medical Department, Beijing You'an Hospital, Capital Medical University, Beijing, China. 4. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. 5. Department of Infectious Disease, Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui, China. 6. Department of Infectious Diseases, Shanghai Ruijin Hospital, Jiaotong University School of Medicine, Shanghai, China. 7. Liver Research Center, First Affiliated Hospital of Fujian Medical University, Fuzhou, China. 8. Department of Hepatology, Peking University People's Hospital, Beijing, China. 9. Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, China. 10. Department of Infectious Disease, Shengjing Hospital of China Medical University, Shenyang, China. 11. Department of Infectious Diseases, Peking University First Hospital, Beijing, China. 12. Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China. 13. Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 14. Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095, Jiefang Avenue, Wuhan, 430030, China. qning@vip.sina.com.
Abstract
BACKGROUND: Switching from nucleos(t)ide analogues to interferon (IFN) improves hepatitis B surface antigen (HBsAg) loss. We aimed to evaluate whether combining immunomodulators such as interleukin-2 (IL-2) and therapeutic vaccine with IFN enhances HBsAg loss in entecavir (ETV)-suppressed patients. METHODS:Ninety-four patients exhibiting virological suppression and hepatitis B e antigen (HBeAg) loss following ETV treatment were randomized 1:1:1 to receive ETV (group I) or IFN (group II) for 48 weeks, or IFN and vaccine for 48 weeks plus IL-2 for 12 weeks (group III). The primary endpoint was HBsAg loss at week 48. Peripheral natural killer (NK) cells and regulatory T cells (Treg) were measured as immune checkpoint indicators. RESULTS:Mean HBsAg decline at week 48 was significantly greater in group III (0.85 log 10 IU/mL) and group II (0.74 log 10 IU/mL), than in group I (0.13 log 10 IU/mL). At week 48, 9.38%, 3.03%, and 3.70% of subjects in group III, II, and I, respectively, achieved HBsAg loss. Among patients with baseline HBsAg titers ranging from 100 to 1500 IU/mL, HBsAg loss rate was 27.3, 7.1, and 0% in group III, II, and I, respectively. Responders in group III showed a significantly higher increase in CD56bright CD16-NK cells from week 24 to 36, and a significant decline in Treg from week 12 to 24 than non-responders. CONCLUSION: For ETV-suppressed patients, particularly those with low baseline HBsAg levels, combination therapy with IFN and other immunomodulators may enhance HBsAg loss, while successful response correlates with partial restoration of NK cells and Tregs.
RCT Entities:
BACKGROUND: Switching from nucleos(t)ide analogues to interferon (IFN) improves hepatitis B surface antigen (HBsAg) loss. We aimed to evaluate whether combining immunomodulators such as interleukin-2 (IL-2) and therapeutic vaccine with IFN enhances HBsAg loss in entecavir (ETV)-suppressed patients. METHODS: Ninety-four patients exhibiting virological suppression and hepatitis B e antigen (HBeAg) loss following ETV treatment were randomized 1:1:1 to receive ETV (group I) or IFN (group II) for 48 weeks, or IFN and vaccine for 48 weeks plus IL-2 for 12 weeks (group III). The primary endpoint was HBsAg loss at week 48. Peripheral natural killer (NK) cells and regulatory T cells (Treg) were measured as immune checkpoint indicators. RESULTS: Mean HBsAg decline at week 48 was significantly greater in group III (0.85 log 10 IU/mL) and group II (0.74 log 10 IU/mL), than in group I (0.13 log 10 IU/mL). At week 48, 9.38%, 3.03%, and 3.70% of subjects in group III, II, and I, respectively, achieved HBsAg loss. Among patients with baseline HBsAg titers ranging from 100 to 1500 IU/mL, HBsAg loss rate was 27.3, 7.1, and 0% in group III, II, and I, respectively. Responders in group III showed a significantly higher increase in CD56bright CD16-NK cells from week 24 to 36, and a significant decline in Treg from week 12 to 24 than non-responders. CONCLUSION: For ETV-suppressed patients, particularly those with low baseline HBsAg levels, combination therapy with IFN and other immunomodulators may enhance HBsAg loss, while successful response correlates with partial restoration of NK cells and Tregs.
Entities:
Keywords:
Combination therapy; Entecavir; Hepatitis B surface antigen loss; Interferon
Authors: George K K Lau; Teerha Piratvisuth; Kang Xian Luo; Patrick Marcellin; Satawat Thongsawat; Graham Cooksley; Edward Gane; Michael W Fried; Wan Cheng Chow; Seung Woon Paik; Wen Yu Chang; Thomas Berg; Robert Flisiak; Philip McCloud; Nigel Pluck Journal: N Engl J Med Date: 2005-06-30 Impact factor: 91.245
Authors: Zheng Zhang; Ji-Yuan Zhang; E John Wherry; Bo Jin; Bin Xu; Zheng-Sheng Zou; Shu-Ye Zhang; Bao-Sen Li; Hui-Feng Wang; Hao Wu; George K K Lau; Yang-Xin Fu; Fu-Sheng Wang Journal: Gastroenterology Date: 2008-03-22 Impact factor: 22.682
Authors: Erik H C J Buster; Hajo J Flink; Yilmaz Cakaloglu; Krzysztof Simon; Jörg Trojan; Fehmi Tabak; Thomas M K So; S Victor Feinman; Tomasz Mach; Ulus S Akarca; Martin Schutten; Wanda Tielemans; Anneke J van Vuuren; Bettina E Hansen; Harry L A Janssen Journal: Gastroenterology Date: 2008-05-15 Impact factor: 22.682
Authors: Ting-Tsung Chang; Robert G Gish; Robert de Man; Adrian Gadano; José Sollano; You-Chen Chao; Anna S Lok; Kwang-Hyub Han; Zachary Goodman; Jin Zhu; Anne Cross; Deborah DeHertogh; Richard Wilber; Richard Colonno; David Apelian Journal: N Engl J Med Date: 2006-03-09 Impact factor: 91.245