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HB eAg levels at week 24 predict response to 8 years of tenofovir in HB eAg‐positive chronic hepatitis B patients
Author(s) -
Wong D.,
Littlejohn M.,
Yuen L.,
Jackson K.,
Mason H.,
Bayliss J.,
Rosenberg G.,
Gaggar A.,
Kitrinos K.,
Subramanian M.,
Marcellin P.,
Buti M.,
Janssen H. L. A.,
Gane E.,
Locarnini S.,
Thompson A.,
Revill P. A.
Publication year - 2018
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.14362
Subject(s) - hbeag , medicine , seroconversion , hbsag , gastroenterology , hepatitis b virus , chronic hepatitis , hepatitis b , immunology , virus
Summary Background Hepatitis B e antigen ( HB eAg) seroconversion is a treatment endpoint for HB eAg‐positive CHB , and a necessary precursor to HB sAg loss. Biomarkers that predict serological outcomes would be useful. Aim To evaluate the utility of measuring HB eAg levels for predicting HB eAg seroconversion and HB sAg loss under long‐term tenofovir ( TDF ) therapy. Methods A total of 266 patients were enrolled into a phase III study of TDF vs adefovir ( ADV ) for 48 weeks in HB eAg‐positive patients, followed by open‐label TDF up to 384 weeks. Serum HB eAg levels were measured for subjects with samples available at both baseline and week 24 of treatment (n = 200). Analysis compared subjects who achieved HB eAg seroconversion by week 384 vs no HB eAg seroconversion. Results HB eAg seroconversion rate was 52% by week 384. Time to HB eAg seroconversion was 80 weeks ( IQR : 36‐162). HB eAg decline at week 24 was associated with HB eAg seroconversion (1.63 vs 0.90 log 10 PEIU /mL, P = .002). The optimal threshold for identifying HB eAg seroconversion was HB eAg decline ≥2.2 log 10 PEIU / mL at week 24, with HB eAg seroconversion achieved by 76% of patients, compared to 44% if HB eAg decline <2.2 log 10 ( P < .0001). HB eAg decline ≥2.2 log 10 PEIU / mL at week 24 was associated with HB sAg loss in genotype A or D patients (38% vs 15%, P = .03). Precore/basal core promotor variants were associated with lower baseline HB eAg levels, but not HB eAg seroconversion. Conclusion Decline in HB eAg levels by week 24 was associated with HB eAg seroconversion and HB sAg loss in HB eAg‐positive chronic hepatitis B patients treated with long‐term TDF .