Hepatitis B surface antigen levels: association with 5-year response to peginterferon alfa-2a in hepatitis B e-antigen-negative patients

Patrick Marcellin, Ferruccio Bonino, Cihan Yurdaydin, Stephanos Hadziyannis, Rami Moucari, Hans-Peter Kapprell, Vivien Rothe, Matei Popescu, Maurizia R Brunetto, Patrick Marcellin, Ferruccio Bonino, Cihan Yurdaydin, Stephanos Hadziyannis, Rami Moucari, Hans-Peter Kapprell, Vivien Rothe, Matei Popescu, Maurizia R Brunetto

Abstract

Purpose: To investigate the durability of response to peginterferon alfa-2a up to 5 years post-treatment and factors associated with response in hepatitis B e-antigen (HBeAg)-negative patients.

Methods: HBeAg-negative patients received peginterferon alfa-2a (180 μg/week) ± lamivudine (100 mg/day) for 48 weeks as part of a multicenter, randomized study. The planned 5-year efficacy analysis included patients (n = 230) enrolled in the long-term follow-up study. On-treatment hepatitis B surface antigen (HBsAg) decline kinetics were analyzed retrospectively in a subgroup of patients with HBsAg data available at baseline, weeks 12, 24, and 48 on-treatment, and 6 months post-treatment (n = 120). Receiver operating characteristic analyses identified the on-treatment HBsAg levels associated with response at 1 and 5 years post-treatment.

Results: HBV DNA ≤2,000 IU/mL and HBsAg clearance at 5 years post-treatment were achieved by 23 and 12% of patients, respectively. High rates of HBsAg clearance at 5 years post-treatment were achieved by patients with HBV DNA ≤2,000 IU/mL at 1 year post-treatment (28%). Rates of HBV DNA ≤2,000 IU/mL at 1 year post-treatment were 47.2 and 43.4% in patients with ≥10% decline from baseline at weeks 12 and 24, respectively, compared with 16.4% (p = 0.0003) and 13.2% (p < 0.0004) in patients with a <10% decline. Rates of HBsAg clearance at 5 years post-treatment were 22.6 and 22.4% in patients with ≥10% decline at weeks 12 and 24, respectively, compared with 7.5% (p = 0.0161) and 3.8% (p < 0.0001) in patients with <10% decline.

Conclusions: Peginterferon alfa-2a results in increasing rates of HBsAg clearance during post-treatment follow-up in HBeAg-negative patients. On-treatment decline in HBsAg is significantly associated with long-term post-treatment response.

Keywords: Chronic hepatitis B; HBV DNA suppression; HBsAg clearance; Long-term response; Prediction.

Figures

Fig. 1
Fig. 1
On-treatment HBsAg decline according to response. a 1 year post-treatment. b 5 years post-treatment. c 1 year (HBV DNA ≤2,000 IU/mL) and 5 years (HBsAg clearance) post-treatment
Fig. 2
Fig. 2
a On-treatment HBsAg decline in responders, relapsers, and non-responders. b On-treatment HBV DNA decline in responders, relapsers, and non-responders treated with peginterferon alfa-2a. c On-treatment HBV DNA decline in responders, relapsers, and non-responders treated with peginterferon alfa-2a + lamivudine. Responder: HBV DNA ≤2,000 IU/mL at end of treatment and year 5; relapser: HBV DNA <2,000 IU/mL at end of treatment; HBV DNA >2,000 IU/mL at year 5; non-responder: HBV DNA >2,000 IU/mL at end of treatment and year 5
Fig. 3
Fig. 3
Response rates at 1 and 5 years post-treatment according to HBsAg decline at week 12 or week 24 of treatment. a Response defined as HBV DNA ≤2,000 IU/mL. b Response defined as HBsAg clearance

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