Premium
A randomized clinical trial of peginterferon alpha‐2b with or without entecavir in patients with HB eAg‐negative chronic hepatitis B: Role of host and viral factors associated with treatment response
Author(s) -
Tangkijvanich P.,
Chittmittraprap S.,
Poovorawan K.,
Limothai U.,
Khlaiphuengsin A.,
Chuaypen N.,
Wisedopas N.,
Poovorawan Y.
Publication year - 2016
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/jvh.12467
Subject(s) - entecavir , hbsag , medicine , gastroenterology , cccdna , hbeag , hepatitis b virus , combination therapy , hepatitis b , immunology , genotype , viral load , virus , lamivudine , biology , gene , biochemistry
Summary 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 HB eAg‐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 IFNL 3 (rs12979860) and HLA ‐ DPA 1 (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 HB sAg 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), HB sAg clearance (9.5% vs 4.8%, P = 0.491) and HB sAg decline. Baseline HB sAg 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 HB sAg clearance (29.4%). None of the patients without decrease in HB sAg combined with <2 log 10 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 HB sAg clearance/decline over monotherapy. Host and viral factors could help optimize decision‐making at baseline and during PEG ‐ IFN ‐based therapy.