HBsAg Loss with Peg-interferon Alfa-2a in Hepatitis B Patients with Partial Response to Nucleos(t)ide Analog: New Switch Study

Peng Hu, Jia Shang, Wenhong Zhang, Guozhong Gong, Yongguo Li, Xinyue Chen, Jianning Jiang, Qing Xie, Xiaoguang Dou, Yongtao Sun, Yufang Li, Yingxia Liu, Guozhen Liu, Dewen Mao, Xiaoling Chi, Hong Tang, Xiaoou Li, Yao Xie, Xiaoping Chen, Jiaji Jiang, Ping Zhao, Jinlin Hou, Zhiliang Gao, Huimin Fan, Jiguang Ding, Dazhi Zhang, Hong Ren, Peng Hu, Jia Shang, Wenhong Zhang, Guozhong Gong, Yongguo Li, Xinyue Chen, Jianning Jiang, Qing Xie, Xiaoguang Dou, Yongtao Sun, Yufang Li, Yingxia Liu, Guozhen Liu, Dewen Mao, Xiaoling Chi, Hong Tang, Xiaoou Li, Yao Xie, Xiaoping Chen, Jiaji Jiang, Ping Zhao, Jinlin Hou, Zhiliang Gao, Huimin Fan, Jiguang Ding, Dazhi Zhang, Hong Ren

Abstract

Background and Aims: Hepatitis B surface antigen (HBsAg) loss is seldom achieved with nucleos(t)ide analog (NA) therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon (Peg-IFN) alfa-2a. We assessed HBsAg loss with 48- and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA. Methods: Hepatitis B e antigen (HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA <200 IU/mL with previous adefovir, lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48 (n = 153) or 96 weeks (n = 150). The primary endpoint of this study was HBsAg loss at end of treatment. The ClinicalTrials.gov identifier is NCT01464281. Results: At the end of 48 and 96 weeks' treatment, 14.4% (22/153) and 20.7% (31/150) of patients, respectively, who switched from NA to Peg-IFN alfa-2a cleared HBsAg. Rates were similar irrespective of prior NA or baseline HBeAg seroconversion. Among those who cleared HBsAg by the end of 48 and 96 weeks' treatment, 77.8% (14/18) and 71.4% (20/28), respectively, sustained HBsAg loss for a further 48 weeks. Baseline HBsAg <1500 IU/mL and week 24 HBsAg <200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48- and 96-week treatment (51.4% and 58.7%, respectively). Importantly, extending treatment from 48 to 96 weeks enabled 48.3% (14/29) more patients to achieve HBsAg loss. Conclusions: Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a. HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks, although the differences in our study cohort were not statistically significant. Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.

Keywords: Antiviral therapy; Chronic hepatitis B; Nucleos(t)ide treated; Peg-interferon.

Conflict of interest statement

Prof. Hou has received grant/research support from Gilead, Novartis, Bristol-Myers Squibb and GlaxoSmithKline, and consulting fees from Gilead. Prof. Ren has received grant/research support from Roche, Novartis, Bristol-Myers Squibb and GlaxoSmithKline. None of the other authors have no conflict of interests related to this publication.

Figures

Fig. 1.. Patient disposition.
Fig. 1.. Patient disposition.
Abbreviations: ITT, intention-to-treat; Peg-IFN, pegylated-interferon.
Fig. 2.. HBsAg, HBV DNA, and ALT…
Fig. 2.. HBsAg, HBV DNA, and ALT levels of responders (HBsAg loss at end of treatment) 48 weeks after treatment discontinuation.
Patients with missing HBsAg data at end of follow-up (four in the week 48 arm and three in the week 96 arm) are not depicted in this diagram. Dotted lines indicate HBsAg threshold of 0.05 IU/mL (blue), HBV DNA 200 IU/mL (red), and ALT 1 × ULN (green). Abbreviations: ALT, alanine aminotransferase; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; Peg-IFN, pegylated-interferon; ULN, upper limit of normal.
Fig. 3.. Decline in mean serum HBsAg…
Fig. 3.. Decline in mean serum HBsAg over time with 48 and 96 weeks of Peg-IFN alfa-2a treatment according to response (HBsAg loss at the end of treatment).
Data shown are mean ± standard deviation. Abbreviations: HBsAg, hepatitis B surface antigen; Peg-IFN, pegylated-interferon.

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