Liver Research Unit, Chang Gung Memorial Hospital-LinKou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Changhua Christian Hospital, Department of Internal Medicine, Changhua, Taiwan.
Chang Gung Memorial Hospital-Kaohsiung, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
China Medical University Hospital, Department of Hepato-Gastroenterology, Taichung, Taiwan.
Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
National Taiwan University Hospital, Department of Hepato-Gastroenterology, Taipei, Taiwan.
Tri-Service Hospital, Department of Internal Medicine, Taipei, Taiwan.
Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
Liver Research Unit, Chang Gung Memorial Hospital-LinKou, Chang Gung University College of Medicine, Taoyuan, Taiwan. Electronic address: email@example.com.
Liver Research Unit, Chang Gung Memorial Hospital-LinKou, Chang Gung University College of Medicine, Taoyuan, Taiwan. Electronic address: firstname.lastname@example.org.
Efficacy of sequential therapy with nucleos(t)ide analogues and interferons versus monotherapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) remains unexplored. We aimed to assess efficacy and safety of sequential therapy with adefovir (ADV) or entecavir (ETV) followed by peginterferon (PEG-IFN) alfa-2a in Taiwanese patients with HBeAg-positive.
This randomized, placebo-controlled, double-blind trial was conducted at nine sites in Taiwan from April 2010 to October 2013. Patients (N = 280) were randomized 1:1:1 to receive placebo, ETV or ADV alone for four weeks, combined with PEG-IFN alfa-2a for two weeks, then PEG-IFN alfa-2a alone for 46 weeks. The primary efficacy end point was HBeAg seroconversion at 48 weeks post-treatment.
No significant differences were observed among groups for HBeAg seroconversion (PEG-IFN alfa-2a+placebo, 36.3%; PEG-IFN alfa-2a+ETV, 29.5%; and PEG-IFN alfa-2a+ADV, 27.4%), HBeAg loss (37.4%, 32.2%, and 28.6%, respectively) or change in hepatitis B surface antigen (HBsAg) levels from baseline (-0.56 IU/mL, -0.60 IU/mL, and -0.41 IU/mL, respectively). However, hepatitis Bvirus DNA levels were higher with PEG-IFN alfa-2a+placebo than PEG-IFN alfa+ETV at week 64 (p = 0.0412), 76 (p = 0.0311), and 88 (p = 0.0113), and alanine aminotransferase (ALT) normalization rate was higher with PEG-IFN alfa-2a+placebo than PEG-IFN alfa-2a+ADV (p = 0.0283) or PEG-IFN alfa-2a+ETV (p = 0.0369) at week 88. Sub-analysis of results revealed an association between on-treatment HBsAg and ALT levels and efficacy 48 weeks post-treatment. Safety was comparable among treatment groups.
Pre-therapy with ADV or ETV followed by PEG-IFN alfa-2a is not superior to PEG-IFN alfa-2a monotherapy in Taiwanese patients with HBeAg-positive CHB.
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