title: A randomized clinical trial of peginterferon alpha-2b with or without entecavir in patients with HBeAg-negative chronic hepatitis B: Role of host and viral factors associated with treatment response.
abstract: Combining peginterferon (PEG-IFN) and a potent nucleoside/nucleotide analogue might improve treatment response in patients with chronic hepatitis B (CHB). The aims of this study were to compare the efficacy of PEG-IFN alpha-2b with or without entecavir in HBeAg-negative CHB and to investigate predictors of response. A total of 126 treatment-naïve patients were randomly assigned to receive monotherapy (n = 63) or combination therapy (n = 63) for 48 weeks. Virological response (VR) was defined as HBV DNA level <2000 IU/mL at week 96. Baseline factors including polymorphisms in the IFNL3 (rs12979860) and HLA-DPA1 (rs3077) genes and on-treatment viral kinetics were determined. At week 48, rates of undetectable HBV DNA were lower in the monotherapy than combination groups, but rates of HBsAg clearance and decline were comparable. At week 96, there was no difference between the corresponding groups regarding virological response (41.3% vs 38.1%, P = 0.856), HBsAg clearance (9.5% vs 4.8%, P = 0.491) and HBsAg decline. Baseline HBsAg level [odds ratio (OR): 3.14 (1.34-7.69), P = 0.012] and rs3077 polymorphism [OR: 2.78 (1.27-6.11), P = 0.011] were independent predictors of response. Patients carried GG genotype of rs3077 with low baseline HBV (<1000 IU/mL) had high probability of achieving VR (76.5%) and HBsAg clearance (29.4%). None of the patients without decrease in HBsAg combined with <2 log10 HBV DNA decline at week 12 achieved a virological response. In conclusion, the combination therapy lead to greater on-treatment HBV DNA suppression but did not improve virological response and HBsAg clearance/decline over monotherapy. Host and viral factors could help optimize decision-making at baseline and during PEG-IFN-based therapy.
authors.affiliation: Research Unit of Hepatitis and Liver Cancer, Department of Biochemistry, Chulalongkorn University, Bangkok, Thailand.
authors.forename: P
authors.initials: P
authors.lastname: Tangkijvanich
authors.affiliation: Department of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: S
authors.initials: S
authors.lastname: Chittmittraprap
authors.affiliation: Department of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: K
authors.initials: K
authors.lastname: Poovorawan
authors.affiliation: Center of Excellence in Clinical Virology, Department of Pediatrics, Chulalongkorn University, Bangkok, Thailand.
authors.forename: U
authors.initials: U
authors.lastname: Limothai
authors.affiliation: Research Unit of Hepatitis and Liver Cancer, Department of Biochemistry, Chulalongkorn University, Bangkok, Thailand.
authors.forename: A
authors.initials: A
authors.lastname: Khlaiphuengsin
authors.affiliation: Research Unit of Hepatitis and Liver Cancer, Department of Biochemistry, Chulalongkorn University, Bangkok, Thailand.
authors.forename: N
authors.initials: N
authors.lastname: Chuaypen
authors.affiliation: Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: N
authors.initials: N
authors.lastname: Wisedopas
authors.affiliation: Center of Excellence in Clinical Virology, Department of Pediatrics, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Y
authors.initials: Y
authors.lastname: Poovorawan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C413685:entecavir; D006147:Guanine; C417083:peginterferon alfa-2b
keywords: HBsAg quantification; entecavir; peginterferon; polymorphisms; stopping rule