Hepatitis B Virus RNA as Early Predictor for Response to Pegylated Interferon Alpha in HBeAg-Negative Chronic Hepatitis B

Mina S. Farag; Margo J.H. Van Campenhout; Maria Pfefferkorn; Janett Fischer; Danilo Deichsel; André Boonstra; Anneke J. Van Vuuren; Peter Ferenci; Jordan J. Feld; Thomas Berg; Bettina E. Hansen; Florian Van Bömmel; Harry L.A. Janssen

doi:10.1093/cid/ciaa013

Hepatitis B Virus RNA as Early Predictor for Response to Pegylated Interferon Alpha in HBeAg-Negative Chronic Hepatitis B

Mina S. Farag, Margo J.H. Van Campenhout, Maria Pfefferkorn, Janett Fischer, Danilo Deichsel, André Boonstra, Anneke J. Van Vuuren, Peter Ferenci, Jordan J. Feld, Thomas Berg, Bettina E. Hansen, Florian Van Bömmel, Harry L.A. Janssen^*

^*Corresponding author for this work

Gastroenterology & Hepatology

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

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Abstract

Background: Hepatitis B virus RNA (HBV-RNA) is a novel serum biomarker that correlates with transcription of intrahepatic covalently closed circular (cccDNA), which is an important target for pegylated interferon (PEG-IFN) and novel therapies for functional cure. We studied HBV-RNA kinetics following PEG-IFN treatment and its potential role as a predictor to response in HBeAg-negative chronic hepatitis B (CHB) patients. Methods: HBV-RNA levels were measured in 133 HBeAg-negative CHB patients treated in an international randomized controlled trial (PARC study). Patients received PEG-IFN α-2a for 48 weeks. HBV-RNA was measured from baseline through week 144. Response was defined as HBV-DNA <2000 IU/mL and ALT normalization at week 72. Kinetics of HBV-RNA were compared with HBV-DNA, HBsAg, and HBcrAg. Results: Mean HBV-RNA at baseline was 4.4 (standard deviation [SD] 1.2) log10 c/mL. At week 12, HBV-RNA declined by -1.6 (1.1) log10 c/mL. HBV-RNA showed a greater decline in responders compared to nonresponders early at week 12 (-2.0 [1.2] vs -1.5 [1.1] log10 c/mL, P=.04). HBV-RNA level above 1700 c/mL (3.2 log10 c/mL) had a negative predictive value of 91% at week 12 and 93% at week 24 (P=.01) for response. Overall, HBV-RNA showed a stronger correlation with HBV-DNA and HBcrAg (.82 and. 80, P<.001) and a weak correlation with HBsAg (.25). At week 12, HBV-RNA was significantly lower among patients with lower HBsAg (<100 IU/mL) or HBsAg loss at week 144. Conclusions: During PEG-IFN treatment for HBeAg-negative CHB, HBV-RNA showed a fast and significant decline that correlates with treatment response and HBsAg loss at long-term follow-up. Clinical Trials Registration: NCT00114361

Original language	English
Pages (from-to)	202-211
Number of pages	10
Journal	Clinical Infectious Diseases
Volume	72
Issue number	2
DOIs	https://doi.org/10.1093/cid/ciaa013
Publication status	Published - 15 Jan 2021

Bibliographical note

Financial support. This study was supported and initiated by the Toronto Centre for Liver Disease, Toronto, Canada and the Foundation for Liver Research, Rotterdam, the Netherlands. For the original studies, financial support, study medication and drug supply were provided by F. Hoffmann-La Roche Ltd (Basel, Switzerland).

Publisher Copyright: © 2020 The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

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Farag, M. S., Van Campenhout, M. J. H., Pfefferkorn, M., Fischer, J., Deichsel, D., Boonstra, A., Van Vuuren, A. J., Ferenci, P., Feld, J. J., Berg, T., Hansen, B. E., Van Bömmel, F., & Janssen, H. L. A. (2021). Hepatitis B Virus RNA as Early Predictor for Response to Pegylated Interferon Alpha in HBeAg-Negative Chronic Hepatitis B. Clinical Infectious Diseases, 72(2), 202-211. https://doi.org/10.1093/cid/ciaa013

@article{fddb2dedf1e343f8b6e097e94620ec97,

title = "Hepatitis B Virus RNA as Early Predictor for Response to Pegylated Interferon Alpha in HBeAg-Negative Chronic Hepatitis B",

abstract = "Background: Hepatitis B virus RNA (HBV-RNA) is a novel serum biomarker that correlates with transcription of intrahepatic covalently closed circular (cccDNA), which is an important target for pegylated interferon (PEG-IFN) and novel therapies for functional cure. We studied HBV-RNA kinetics following PEG-IFN treatment and its potential role as a predictor to response in HBeAg-negative chronic hepatitis B (CHB) patients. Methods: HBV-RNA levels were measured in 133 HBeAg-negative CHB patients treated in an international randomized controlled trial (PARC study). Patients received PEG-IFN α-2a for 48 weeks. HBV-RNA was measured from baseline through week 144. Response was defined as HBV-DNA <2000 IU/mL and ALT normalization at week 72. Kinetics of HBV-RNA were compared with HBV-DNA, HBsAg, and HBcrAg. Results: Mean HBV-RNA at baseline was 4.4 (standard deviation [SD] 1.2) log10 c/mL. At week 12, HBV-RNA declined by -1.6 (1.1) log10 c/mL. HBV-RNA showed a greater decline in responders compared to nonresponders early at week 12 (-2.0 [1.2] vs -1.5 [1.1] log10 c/mL, P=.04). HBV-RNA level above 1700 c/mL (3.2 log10 c/mL) had a negative predictive value of 91% at week 12 and 93% at week 24 (P=.01) for response. Overall, HBV-RNA showed a stronger correlation with HBV-DNA and HBcrAg (.82 and. 80, P<.001) and a weak correlation with HBsAg (.25). At week 12, HBV-RNA was significantly lower among patients with lower HBsAg (<100 IU/mL) or HBsAg loss at week 144. Conclusions: During PEG-IFN treatment for HBeAg-negative CHB, HBV-RNA showed a fast and significant decline that correlates with treatment response and HBsAg loss at long-term follow-up. Clinical Trials Registration: NCT00114361",

author = "Farag, {Mina S.} and {Van Campenhout}, {Margo J.H.} and Maria Pfefferkorn and Janett Fischer and Danilo Deichsel and Andr{\'e} Boonstra and {Van Vuuren}, {Anneke J.} and Peter Ferenci and Feld, {Jordan J.} and Thomas Berg and Hansen, {Bettina E.} and {Van B{\"o}mmel}, Florian and Janssen, {Harry L.A.}",

note = "Financial support. This study was supported and initiated by the Toronto Centre for Liver Disease, Toronto, Canada and the Foundation for Liver Research, Rotterdam, the Netherlands. For the original studies, financial support, study medication and drug supply were provided by F. Hoffmann-La Roche Ltd (Basel, Switzerland). Publisher Copyright: {\textcopyright} 2020 The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.",

year = "2021",

month = jan,

day = "15",

doi = "10.1093/cid/ciaa013",

language = "English",

volume = "72",

pages = "202--211",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

publisher = "Oxford University Press",

number = "2",

}

Farag, MS, Van Campenhout, MJH, Pfefferkorn, M, Fischer, J, Deichsel, D, Boonstra, A , Van Vuuren, AJ, Ferenci, P, Feld, JJ, Berg, T, Hansen, BE, Van Bömmel, F & Janssen, HLA 2021, 'Hepatitis B Virus RNA as Early Predictor for Response to Pegylated Interferon Alpha in HBeAg-Negative Chronic Hepatitis B', Clinical Infectious Diseases, vol. 72, no. 2, pp. 202-211. https://doi.org/10.1093/cid/ciaa013

TY - JOUR

T1 - Hepatitis B Virus RNA as Early Predictor for Response to Pegylated Interferon Alpha in HBeAg-Negative Chronic Hepatitis B

AU - Farag, Mina S.

AU - Van Campenhout, Margo J.H.

AU - Pfefferkorn, Maria

AU - Fischer, Janett

AU - Deichsel, Danilo

AU - Boonstra, André

AU - Van Vuuren, Anneke J.

AU - Ferenci, Peter

AU - Feld, Jordan J.

AU - Berg, Thomas

AU - Hansen, Bettina E.

AU - Van Bömmel, Florian

AU - Janssen, Harry L.A.

N1 - Financial support. This study was supported and initiated by the Toronto Centre for Liver Disease, Toronto, Canada and the Foundation for Liver Research, Rotterdam, the Netherlands. For the original studies, financial support, study medication and drug supply were provided by F. Hoffmann-La Roche Ltd (Basel, Switzerland). Publisher Copyright: © 2020 The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

PY - 2021/1/15

Y1 - 2021/1/15

N2 - Background: Hepatitis B virus RNA (HBV-RNA) is a novel serum biomarker that correlates with transcription of intrahepatic covalently closed circular (cccDNA), which is an important target for pegylated interferon (PEG-IFN) and novel therapies for functional cure. We studied HBV-RNA kinetics following PEG-IFN treatment and its potential role as a predictor to response in HBeAg-negative chronic hepatitis B (CHB) patients. Methods: HBV-RNA levels were measured in 133 HBeAg-negative CHB patients treated in an international randomized controlled trial (PARC study). Patients received PEG-IFN α-2a for 48 weeks. HBV-RNA was measured from baseline through week 144. Response was defined as HBV-DNA <2000 IU/mL and ALT normalization at week 72. Kinetics of HBV-RNA were compared with HBV-DNA, HBsAg, and HBcrAg. Results: Mean HBV-RNA at baseline was 4.4 (standard deviation [SD] 1.2) log10 c/mL. At week 12, HBV-RNA declined by -1.6 (1.1) log10 c/mL. HBV-RNA showed a greater decline in responders compared to nonresponders early at week 12 (-2.0 [1.2] vs -1.5 [1.1] log10 c/mL, P=.04). HBV-RNA level above 1700 c/mL (3.2 log10 c/mL) had a negative predictive value of 91% at week 12 and 93% at week 24 (P=.01) for response. Overall, HBV-RNA showed a stronger correlation with HBV-DNA and HBcrAg (.82 and. 80, P<.001) and a weak correlation with HBsAg (.25). At week 12, HBV-RNA was significantly lower among patients with lower HBsAg (<100 IU/mL) or HBsAg loss at week 144. Conclusions: During PEG-IFN treatment for HBeAg-negative CHB, HBV-RNA showed a fast and significant decline that correlates with treatment response and HBsAg loss at long-term follow-up. Clinical Trials Registration: NCT00114361

AB - Background: Hepatitis B virus RNA (HBV-RNA) is a novel serum biomarker that correlates with transcription of intrahepatic covalently closed circular (cccDNA), which is an important target for pegylated interferon (PEG-IFN) and novel therapies for functional cure. We studied HBV-RNA kinetics following PEG-IFN treatment and its potential role as a predictor to response in HBeAg-negative chronic hepatitis B (CHB) patients. Methods: HBV-RNA levels were measured in 133 HBeAg-negative CHB patients treated in an international randomized controlled trial (PARC study). Patients received PEG-IFN α-2a for 48 weeks. HBV-RNA was measured from baseline through week 144. Response was defined as HBV-DNA <2000 IU/mL and ALT normalization at week 72. Kinetics of HBV-RNA were compared with HBV-DNA, HBsAg, and HBcrAg. Results: Mean HBV-RNA at baseline was 4.4 (standard deviation [SD] 1.2) log10 c/mL. At week 12, HBV-RNA declined by -1.6 (1.1) log10 c/mL. HBV-RNA showed a greater decline in responders compared to nonresponders early at week 12 (-2.0 [1.2] vs -1.5 [1.1] log10 c/mL, P=.04). HBV-RNA level above 1700 c/mL (3.2 log10 c/mL) had a negative predictive value of 91% at week 12 and 93% at week 24 (P=.01) for response. Overall, HBV-RNA showed a stronger correlation with HBV-DNA and HBcrAg (.82 and. 80, P<.001) and a weak correlation with HBsAg (.25). At week 12, HBV-RNA was significantly lower among patients with lower HBsAg (<100 IU/mL) or HBsAg loss at week 144. Conclusions: During PEG-IFN treatment for HBeAg-negative CHB, HBV-RNA showed a fast and significant decline that correlates with treatment response and HBsAg loss at long-term follow-up. Clinical Trials Registration: NCT00114361

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U2 - 10.1093/cid/ciaa013

DO - 10.1093/cid/ciaa013

M3 - Article

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AN - SCOPUS:85086937961

SN - 1058-4838

VL - 72

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EP - 211

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

IS - 2

ER -

Hepatitis B Virus RNA as Early Predictor for Response to Pegylated Interferon Alpha in HBeAg-Negative Chronic Hepatitis B

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