Abstract
Nucleos(t)ide analogues (NAs) and peginterferon have complementary effects in chronic hepatitis B, but it is unclear whether combination therapy improves responses in genotype D-infected patients. We conducted an open-label study of peginterferon alfa-2a 180 μg/wk added to ongoing NA therapy in hepatitis B e antigen (HBeAg)-negative, genotype D-infected patients with hepatitis B virus DNA <20 IU/mL. The primary endpoint was proportion of patients with ≥50% decline in serum HBsAg by the end of the 48-week add-on phase. Seventy patients received treatment, 11 were withdrawn at week 24 for no decrease in HBsAg, and 14 withdrew for other reasons. Response rate (per-protocol population) was 67.4% (29/43) at week 48 (95% confidence interval [CI]: 51, 81) and 50.9% (28/55) at week 96 (95% CI: 38, 66). Median serum HBsAg decreased throughout peginterferon alfa-2a treatment and was significantly lower than baseline at weeks 48, 72 and 96 (P < 0.001). Decreases in HBsAg of ≥0.5-log10 and ≥1-log10 were documented in 19 (44.2%) and 6 (14.0%) patients at week 48 and 6 (10.9%) and 17 (30.9%) patients at week 96. The proportion of patients with HBsAg <1000, <500, <100 and <10 IU/mL at ≥1 timepoint during treatment was 78.6% (n = 44), 57.1% (n = 32), 21.4% (n = 12) and 7.1% (n = 4). Interferon gamma-induced protein 10 increased from baseline up to week 48, with week 12 levels significantly associated with response at week 48. Addition of peginterferon alfa-2a to ongoing NA therapy significantly decreased HBsAg levels in HBeAg-negative patients with genotype D infection (ClinicalTrials.gov NCT01706575).
| Original language | English |
|---|---|
| Pages (from-to) | 118-125 |
| Journal | Journal of Viral Hepatitis |
| Volume | 26 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2019 |
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Keywords
- chronic hepatitis B
- HBeAg-negative
- nucleos(t)ide analogues
- peginterferon
- treatment
ASJC Scopus subject areas
- Hepatology
- Infectious Diseases
- Virology
Cite this
Add-on peginterferon alfa-2a to nucleos(t)ide analogue therapy for Caucasian patients with hepatitis B ‘e’ antigen-negative chronic hepatitis B genotype D. / The HERMES Study Group ; Lampertico, Pietro; Brunetto, Maurizia R.; Craxì, Antonio; Gaeta, Giovanni B.; Rizzetto, Mario; Rozzi, Antonella; Colombo, Massimo.
In: Journal of Viral Hepatitis, Vol. 26, No. 1, 2019, p. 118-125.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Add-on peginterferon alfa-2a to nucleos(t)ide analogue therapy for Caucasian patients with hepatitis B ‘e’ antigen-negative chronic hepatitis B genotype D
AU - The HERMES Study Group
AU - Lampertico, Pietro
AU - Brunetto, Maurizia R.
AU - Craxì, Antonio
AU - Gaeta, Giovanni B.
AU - Rizzetto, Mario
AU - Rozzi, Antonella
AU - Colombo, Massimo
AU - Antonio, D.
AU - Andreone, P.
AU - Antonio, D.
AU - Brancaccio, G.
AU - Bronte, F.
AU - Bruzzone, L.
AU - Caccamo, G.
AU - Caccianotti, B.
AU - Calvaruso, V.
AU - Chessa, L.
AU - Ciarallo, M.
AU - Coco, B.
AU - Colombatto, P.
AU - Cursaro, C.
AU - D'Aluisio, D.
AU - Demelia, L.
AU - Di Marco, V.
AU - Dissegna, D.
AU - Invernizzi, F.
AU - Lenisa, I.
AU - Lembo, T.
AU - Levrero, M.
AU - Marchese, V.
AU - Mangia, G.
AU - Picciotto, A.
AU - Pierconti, S.
AU - Antonio, D.
AU - Raimondo, G.
AU - Rastelli, C.
AU - Rizzo, V.
AU - Santantonio, T.
AU - Scuteri, A.
AU - Sorbello, O.
AU - Squadrito, G.
AU - Subic, M.
AU - Toniutto, P.
AU - Vukotic, R.
PY - 2019
Y1 - 2019
N2 - Nucleos(t)ide analogues (NAs) and peginterferon have complementary effects in chronic hepatitis B, but it is unclear whether combination therapy improves responses in genotype D-infected patients. We conducted an open-label study of peginterferon alfa-2a 180 μg/wk added to ongoing NA therapy in hepatitis B e antigen (HBeAg)-negative, genotype D-infected patients with hepatitis B virus DNA <20 IU/mL. The primary endpoint was proportion of patients with ≥50% decline in serum HBsAg by the end of the 48-week add-on phase. Seventy patients received treatment, 11 were withdrawn at week 24 for no decrease in HBsAg, and 14 withdrew for other reasons. Response rate (per-protocol population) was 67.4% (29/43) at week 48 (95% confidence interval [CI]: 51, 81) and 50.9% (28/55) at week 96 (95% CI: 38, 66). Median serum HBsAg decreased throughout peginterferon alfa-2a treatment and was significantly lower than baseline at weeks 48, 72 and 96 (P < 0.001). Decreases in HBsAg of ≥0.5-log10 and ≥1-log10 were documented in 19 (44.2%) and 6 (14.0%) patients at week 48 and 6 (10.9%) and 17 (30.9%) patients at week 96. The proportion of patients with HBsAg <1000, <500, <100 and <10 IU/mL at ≥1 timepoint during treatment was 78.6% (n = 44), 57.1% (n = 32), 21.4% (n = 12) and 7.1% (n = 4). Interferon gamma-induced protein 10 increased from baseline up to week 48, with week 12 levels significantly associated with response at week 48. Addition of peginterferon alfa-2a to ongoing NA therapy significantly decreased HBsAg levels in HBeAg-negative patients with genotype D infection (ClinicalTrials.gov NCT01706575).
AB - Nucleos(t)ide analogues (NAs) and peginterferon have complementary effects in chronic hepatitis B, but it is unclear whether combination therapy improves responses in genotype D-infected patients. We conducted an open-label study of peginterferon alfa-2a 180 μg/wk added to ongoing NA therapy in hepatitis B e antigen (HBeAg)-negative, genotype D-infected patients with hepatitis B virus DNA <20 IU/mL. The primary endpoint was proportion of patients with ≥50% decline in serum HBsAg by the end of the 48-week add-on phase. Seventy patients received treatment, 11 were withdrawn at week 24 for no decrease in HBsAg, and 14 withdrew for other reasons. Response rate (per-protocol population) was 67.4% (29/43) at week 48 (95% confidence interval [CI]: 51, 81) and 50.9% (28/55) at week 96 (95% CI: 38, 66). Median serum HBsAg decreased throughout peginterferon alfa-2a treatment and was significantly lower than baseline at weeks 48, 72 and 96 (P < 0.001). Decreases in HBsAg of ≥0.5-log10 and ≥1-log10 were documented in 19 (44.2%) and 6 (14.0%) patients at week 48 and 6 (10.9%) and 17 (30.9%) patients at week 96. The proportion of patients with HBsAg <1000, <500, <100 and <10 IU/mL at ≥1 timepoint during treatment was 78.6% (n = 44), 57.1% (n = 32), 21.4% (n = 12) and 7.1% (n = 4). Interferon gamma-induced protein 10 increased from baseline up to week 48, with week 12 levels significantly associated with response at week 48. Addition of peginterferon alfa-2a to ongoing NA therapy significantly decreased HBsAg levels in HBeAg-negative patients with genotype D infection (ClinicalTrials.gov NCT01706575).
KW - chronic hepatitis B
KW - HBeAg-negative
KW - nucleos(t)ide analogues
KW - peginterferon
KW - treatment
UR - http://www.scopus.com/inward/record.url?scp=85058216988&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85058216988&partnerID=8YFLogxK
U2 - 10.1111/jvh.12999
DO - 10.1111/jvh.12999
M3 - Article
AN - SCOPUS:85058216988
VL - 26
SP - 118
EP - 125
JO - Journal of Viral Hepatitis
JF - Journal of Viral Hepatitis
SN - 1352-0504
IS - 1
ER -