Ultra-Long-term Follow-up of Interferon Alfa Treatment for HBeAg-Positive Chronic Hepatitis B Virus Infection

Hannah S.J. Choi; Margo J.H. van Campenhout; Anneke J. van Vuuren; Lisette A.P. Krassenburg; Milan J. Sonneveld; Robert J. de Knegt; Bettina E. Hansen; Harry L.A. Janssen

doi:10.1016/j.cgh.2020.09.004

Ultra-Long-term Follow-up of Interferon Alfa Treatment for HBeAg-Positive Chronic Hepatitis B Virus Infection

Hannah S.J. Choi, Margo J.H. van Campenhout, Anneke J. van Vuuren, Lisette A.P. Krassenburg, Milan J. Sonneveld, Robert J. de Knegt, Bettina E. Hansen, Harry L.A. Janssen^*

^*Corresponding author for this work

Gastroenterology & Hepatology

Research output: Contribution to journal › Article › Academic › peer-review

17 Citations (Scopus)

Abstract

Background and Aims: Interferon-alpha (IFN-α) treatment for chronic hepatitis B (CHB) virus infection is finite and leads to relatively higher functional cure rates (HBsAg loss) than nucleo(s)tide analogue (NA) therapy. Effects of pegylated (PEG)/conventional IFN-α treatment on clinical outcomes were evaluated in an ultra-long-term follow-up of CHB patients. Methods: HBeAg-positive patients treated with (PEG)IFN-α at a tertiary referral centre between 1977-2014 were included. We reviewed medical charts and consulted the municipal registry for patient information. Patients were invited for a single visit at the outpatient clinic in the case of missing follow-up data. The endpoints included serum HBeAg/HBsAg loss and incidence of clinical events, using life table methods and person-years to analyze the incidence of events. Patients were censored upon retreatment. Results: The study cohort included 267 patients, 67% male, 58% Caucasian, with a median age of 32 years. The median follow-up duration was 11.5 years. The 5 and 10-year cumulative incidence of HBsAg loss were 14% and 32%, respectively. Baseline factors associated with a higher rate of HBsAg loss were male sex, Caucasian race, genotype A, age ≥40 years, and cirrhosis. HBsAg loss rates did not differ significantly between those who received short-term (≤24 weeks) vs long-term (>24 weeks) therapy. Both HBeAg and HBsAg loss were significantly associated with improved clinical outcomes. Early response (HBeAg loss) was associated with more HBsAg loss and better patient outcomes. Conclusions: During long-term follow-up, high rates of HBsAg loss were observed from a single (PEG)IFN-α course. Its persistent effects suggest that a role for IFN-α remains, potentially in novel combination therapies in search of a functional cure.

Original language	English
Pages (from-to)	1933-1940.e1
Journal	Clinical Gastroenterology and Hepatology
Volume	19
Issue number	9
DOIs	https://doi.org/10.1016/j.cgh.2020.09.004
Publication status	Published - 1 Sept 2021

Bibliographical note

Funding Information:
Conflicts of interest These authors disclose the following: Milan J. Sonneveld has received speakers? fees and research support from Fujirebio, Roche, Gilead, and BMS; Robert J. de Knegt has received grants from Gilead Sciences and Janssen and has served as a consultant for Gilead Sciences and AbbVie. Bettina Hansen has received grants from Intercept and CymaBay and has served as a consultant for Intercept, CymaBay, Albireo, Mirum, and ChemomAb. Harry Janssen has received grants from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen, MedImmune, Merck, and Roche; and has served as a consultant for AbbVie, Benitec, Bristol-Myers Squibb, Gilead Sciences, Janssen, MedImmune, Merck, Roche, Arbutus, and Vir Biotechnology Inc. The remaining authors disclose no conflicts.

Funding Information:
Conflicts of interest These authors disclose the following: Milan J. Sonneveld has received speakers’ fees and research support from Fujirebio, Roche, Gilead, and BMS; Robert J. de Knegt has received grants from Gilead Sciences and Janssen and has served as a consultant for Gilead Sciences and AbbVie. Bettina Hansen has received grants from Intercept and CymaBay and has served as a consultant for Intercept, CymaBay, Albireo, Mirum, and ChemomAb. Harry Janssen has received grants from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen, MedImmune, Merck, and Roche; and has served as a consultant for AbbVie, Benitec, Bristol-Myers Squibb, Gilead Sciences, Janssen, MedImmune, Merck, Roche, Arbutus, and Vir Biotechnology Inc. The remaining authors disclose no conflicts.

Publisher Copyright:
© 2021 AGA Institute

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Choi, H. S. J., van Campenhout, M. J. H., van Vuuren, A. J., Krassenburg, L. A. P., Sonneveld, M. J., de Knegt, R. J., Hansen, B. E., & Janssen, H. L. A. (2021). Ultra-Long-term Follow-up of Interferon Alfa Treatment for HBeAg-Positive Chronic Hepatitis B Virus Infection. Clinical Gastroenterology and Hepatology, 19(9), 1933-1940.e1. https://doi.org/10.1016/j.cgh.2020.09.004

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title = "Ultra-Long-term Follow-up of Interferon Alfa Treatment for HBeAg-Positive Chronic Hepatitis B Virus Infection",

abstract = "Background and Aims: Interferon-alpha (IFN-α) treatment for chronic hepatitis B (CHB) virus infection is finite and leads to relatively higher functional cure rates (HBsAg loss) than nucleo(s)tide analogue (NA) therapy. Effects of pegylated (PEG)/conventional IFN-α treatment on clinical outcomes were evaluated in an ultra-long-term follow-up of CHB patients. Methods: HBeAg-positive patients treated with (PEG)IFN-α at a tertiary referral centre between 1977-2014 were included. We reviewed medical charts and consulted the municipal registry for patient information. Patients were invited for a single visit at the outpatient clinic in the case of missing follow-up data. The endpoints included serum HBeAg/HBsAg loss and incidence of clinical events, using life table methods and person-years to analyze the incidence of events. Patients were censored upon retreatment. Results: The study cohort included 267 patients, 67% male, 58% Caucasian, with a median age of 32 years. The median follow-up duration was 11.5 years. The 5 and 10-year cumulative incidence of HBsAg loss were 14% and 32%, respectively. Baseline factors associated with a higher rate of HBsAg loss were male sex, Caucasian race, genotype A, age ≥40 years, and cirrhosis. HBsAg loss rates did not differ significantly between those who received short-term (≤24 weeks) vs long-term (>24 weeks) therapy. Both HBeAg and HBsAg loss were significantly associated with improved clinical outcomes. Early response (HBeAg loss) was associated with more HBsAg loss and better patient outcomes. Conclusions: During long-term follow-up, high rates of HBsAg loss were observed from a single (PEG)IFN-α course. Its persistent effects suggest that a role for IFN-α remains, potentially in novel combination therapies in search of a functional cure.",

author = "Choi, {Hannah S.J.} and {van Campenhout}, {Margo J.H.} and {van Vuuren}, {Anneke J.} and Krassenburg, {Lisette A.P.} and Sonneveld, {Milan J.} and {de Knegt}, {Robert J.} and Hansen, {Bettina E.} and Janssen, {Harry L.A.}",

note = "Funding Information: Conflicts of interest These authors disclose the following: Milan J. Sonneveld has received speakers? fees and research support from Fujirebio, Roche, Gilead, and BMS; Robert J. de Knegt has received grants from Gilead Sciences and Janssen and has served as a consultant for Gilead Sciences and AbbVie. Bettina Hansen has received grants from Intercept and CymaBay and has served as a consultant for Intercept, CymaBay, Albireo, Mirum, and ChemomAb. Harry Janssen has received grants from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen, MedImmune, Merck, and Roche; and has served as a consultant for AbbVie, Benitec, Bristol-Myers Squibb, Gilead Sciences, Janssen, MedImmune, Merck, Roche, Arbutus, and Vir Biotechnology Inc. The remaining authors disclose no conflicts. Funding Information: Conflicts of interest These authors disclose the following: Milan J. Sonneveld has received speakers{\textquoteright} fees and research support from Fujirebio, Roche, Gilead, and BMS; Robert J. de Knegt has received grants from Gilead Sciences and Janssen and has served as a consultant for Gilead Sciences and AbbVie. Bettina Hansen has received grants from Intercept and CymaBay and has served as a consultant for Intercept, CymaBay, Albireo, Mirum, and ChemomAb. Harry Janssen has received grants from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen, MedImmune, Merck, and Roche; and has served as a consultant for AbbVie, Benitec, Bristol-Myers Squibb, Gilead Sciences, Janssen, MedImmune, Merck, Roche, Arbutus, and Vir Biotechnology Inc. The remaining authors disclose no conflicts. Publisher Copyright: {\textcopyright} 2021 AGA Institute",

year = "2021",

month = sep,

day = "1",

doi = "10.1016/j.cgh.2020.09.004",

language = "English",

volume = "19",

pages = "1933--1940.e1",

journal = "Clinical Gastroenterology and Hepatology",

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TY - JOUR

T1 - Ultra-Long-term Follow-up of Interferon Alfa Treatment for HBeAg-Positive Chronic Hepatitis B Virus Infection

AU - Choi, Hannah S.J.

AU - van Campenhout, Margo J.H.

AU - van Vuuren, Anneke J.

AU - Krassenburg, Lisette A.P.

AU - Sonneveld, Milan J.

AU - de Knegt, Robert J.

AU - Hansen, Bettina E.

AU - Janssen, Harry L.A.

N1 - Funding Information: Conflicts of interest These authors disclose the following: Milan J. Sonneveld has received speakers? fees and research support from Fujirebio, Roche, Gilead, and BMS; Robert J. de Knegt has received grants from Gilead Sciences and Janssen and has served as a consultant for Gilead Sciences and AbbVie. Bettina Hansen has received grants from Intercept and CymaBay and has served as a consultant for Intercept, CymaBay, Albireo, Mirum, and ChemomAb. Harry Janssen has received grants from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen, MedImmune, Merck, and Roche; and has served as a consultant for AbbVie, Benitec, Bristol-Myers Squibb, Gilead Sciences, Janssen, MedImmune, Merck, Roche, Arbutus, and Vir Biotechnology Inc. The remaining authors disclose no conflicts. Funding Information: Conflicts of interest These authors disclose the following: Milan J. Sonneveld has received speakers’ fees and research support from Fujirebio, Roche, Gilead, and BMS; Robert J. de Knegt has received grants from Gilead Sciences and Janssen and has served as a consultant for Gilead Sciences and AbbVie. Bettina Hansen has received grants from Intercept and CymaBay and has served as a consultant for Intercept, CymaBay, Albireo, Mirum, and ChemomAb. Harry Janssen has received grants from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen, MedImmune, Merck, and Roche; and has served as a consultant for AbbVie, Benitec, Bristol-Myers Squibb, Gilead Sciences, Janssen, MedImmune, Merck, Roche, Arbutus, and Vir Biotechnology Inc. The remaining authors disclose no conflicts. Publisher Copyright: © 2021 AGA Institute

PY - 2021/9/1

Y1 - 2021/9/1

N2 - Background and Aims: Interferon-alpha (IFN-α) treatment for chronic hepatitis B (CHB) virus infection is finite and leads to relatively higher functional cure rates (HBsAg loss) than nucleo(s)tide analogue (NA) therapy. Effects of pegylated (PEG)/conventional IFN-α treatment on clinical outcomes were evaluated in an ultra-long-term follow-up of CHB patients. Methods: HBeAg-positive patients treated with (PEG)IFN-α at a tertiary referral centre between 1977-2014 were included. We reviewed medical charts and consulted the municipal registry for patient information. Patients were invited for a single visit at the outpatient clinic in the case of missing follow-up data. The endpoints included serum HBeAg/HBsAg loss and incidence of clinical events, using life table methods and person-years to analyze the incidence of events. Patients were censored upon retreatment. Results: The study cohort included 267 patients, 67% male, 58% Caucasian, with a median age of 32 years. The median follow-up duration was 11.5 years. The 5 and 10-year cumulative incidence of HBsAg loss were 14% and 32%, respectively. Baseline factors associated with a higher rate of HBsAg loss were male sex, Caucasian race, genotype A, age ≥40 years, and cirrhosis. HBsAg loss rates did not differ significantly between those who received short-term (≤24 weeks) vs long-term (>24 weeks) therapy. Both HBeAg and HBsAg loss were significantly associated with improved clinical outcomes. Early response (HBeAg loss) was associated with more HBsAg loss and better patient outcomes. Conclusions: During long-term follow-up, high rates of HBsAg loss were observed from a single (PEG)IFN-α course. Its persistent effects suggest that a role for IFN-α remains, potentially in novel combination therapies in search of a functional cure.

AB - Background and Aims: Interferon-alpha (IFN-α) treatment for chronic hepatitis B (CHB) virus infection is finite and leads to relatively higher functional cure rates (HBsAg loss) than nucleo(s)tide analogue (NA) therapy. Effects of pegylated (PEG)/conventional IFN-α treatment on clinical outcomes were evaluated in an ultra-long-term follow-up of CHB patients. Methods: HBeAg-positive patients treated with (PEG)IFN-α at a tertiary referral centre between 1977-2014 were included. We reviewed medical charts and consulted the municipal registry for patient information. Patients were invited for a single visit at the outpatient clinic in the case of missing follow-up data. The endpoints included serum HBeAg/HBsAg loss and incidence of clinical events, using life table methods and person-years to analyze the incidence of events. Patients were censored upon retreatment. Results: The study cohort included 267 patients, 67% male, 58% Caucasian, with a median age of 32 years. The median follow-up duration was 11.5 years. The 5 and 10-year cumulative incidence of HBsAg loss were 14% and 32%, respectively. Baseline factors associated with a higher rate of HBsAg loss were male sex, Caucasian race, genotype A, age ≥40 years, and cirrhosis. HBsAg loss rates did not differ significantly between those who received short-term (≤24 weeks) vs long-term (>24 weeks) therapy. Both HBeAg and HBsAg loss were significantly associated with improved clinical outcomes. Early response (HBeAg loss) was associated with more HBsAg loss and better patient outcomes. Conclusions: During long-term follow-up, high rates of HBsAg loss were observed from a single (PEG)IFN-α course. Its persistent effects suggest that a role for IFN-α remains, potentially in novel combination therapies in search of a functional cure.

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SP - 1933-1940.e1

JO - Clinical Gastroenterology and Hepatology

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ER -

Ultra-Long-term Follow-up of Interferon Alfa Treatment for HBeAg-Positive Chronic Hepatitis B Virus Infection

Abstract

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