TITLE: Sustained immune control in HBeAg-positive chronic hepatitis B patients who switched from long-term entecavir therapy to peginterferon alfa-2a (40KD): 1-year follow-up of the OSST study
AUTHORS (FIRST NAME, LAST NAME): Meifang Han1, Jia-ji Jiang2, Jinlin Hou3, Deming Tan4, Yongtao Sun5, Mianzhi Zhao6, Qin Ning1
Institutional Author(s):
INSTITUTIONS (ALL): 1. Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
2. The First Hospital, Fujian Medical University, Fuzhou, China.
3. Nanfang Hospital, Nanfang Medical University, Guangzhou, China.
4. Xiangya Hospital, Central South University, Changsha, China.
5. Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
6. Shanghai Roche Pharmaceutical Co., Ltd, Shanghai, China.
ABSTRACT BODY: Background
Chronic hepatitis B (CHB) patients on nucleos(t)ide analog therapy can achieve maintained hepatitis B virus (HBV) DNA suppression, but over 75% do not achieve sustained immune control (hepatitis B e antigen [HBeAg] seroconversion post-treatment) and potentially require lifelong therapy. In the OSST study, HBeAg-positive patients who switched from long-term entecavir (ETV) therapy (0.5 mg QD for 9–36 months) to 48 weeks of peginterferon alfa-2a (40KD) (PegIFN alfa-2a) achieved higher rates of response (HBeAg seroconversion and hepatitis B surface antigen [HBsAg] loss) than those who continued ETV therapy. This 1-year follow-up study aimed to evaluate the sustainability of response in patients who switch from long-term ETV therapy to finite PegIFN alfa-2a therapy.
Methods
Sixty-two patients from the PegIFN alfa-2a arm of the OSST study (five centers) who completed 48 weeks of treatment were followed up for an additional 48 weeks. Primary endpoints were HBeAg seroconversion and maintenance of HBeAg seroconversion at 48 weeks post-treatment. Secondary endpoints included HBsAg loss, HBV DNA <1000 copies/mL and alanine aminotransferase (ALT) normalization (<1 x upper limit of normal [ULN]).
Results
HBeAg seroconversion rate increased from 17.7% (11/62) at the end of treatment to 38.7% (24/62) 48 weeks after discontinuation of PegIFN alfa-2a therapy. 63.6% (7/11) of patients who seroconverted at the end of treatment sustained response 48 weeks post-treatment, while 33.3% (17/51) of those who did not respond at end of treatment achieved delayed seroconversion. Almost all patients (6/7) with HBsAg loss at the end of treatment achieved sustained response 48 weeks post-treatment. HBV DNA suppression maintained at <1000 copies/mL was achieved in 60% (27/45) of patients (Table).
Conclusion
In patients who do not achieve HBeAg seroconversion despite virological suppression on long-term ETV therapy, switching to a finite course of PegIFN alfa-2a resulted in an increased rate of HBeAg seroconversion (17.7% at end of treatment to 38.7% 48 weeks post-treatment), and sustained HBeAg seroconversion (63.6%) and HBsAg loss (85.7%) 1 year after discontinuation of PegIFN alfa-2a therapy.
Response at end of treatment and 48 weeks post-treatment
Response variable, % (n) End of treatment(N=62) 48 weeks post-treatment(N=62) Sustained response
HBeAg loss 71.0 (44) 67.7 (42) 72.7 (32/44)
HBeAg seroconversion 17.7 (11) 38.7 (24) 63.6 (7/11)
HBsAg loss 11.3 (7) 9.7 (6) 85.7 (6/7)
HBsAg seroconversion 6.5 (4) 4.8 (3) 75.0 (3/4)
HBV DNA <1000 copies/mL 72.6 (45) 53.3 (32/60)* 60 (27/45)
ALT normalization (<1 x ULN) 61.3 (38) 65.0 (39/60)* 75.0 (27/36)*
*Two patients with missing data are excluded.
