Research ExplorerPublicationsImmune cell responses are not required to induce substantial...

Immune cell responses are not required to induce substantial hepatitis B virus antigen decline during pegylated interferon-alpha administration

Standard

Immune cell responses are not required to induce substantial hepatitis B virus antigen decline during pegylated interferon-alpha administration. / Allweiss, Lena; Volz, Tassilo; Lütgehetmann, Marc; Giersch, Katja; Bornscheuer, Till; Lohse, Ansgar W; Petersen, Joerg; Ma, Han; Klumpp, Klaus; Fletcher, Simon P; Dandri, Maura.

In: J HEPATOL, Vol. 60, No. 3, 01.03.2014, p. 500-7.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Allweiss, L, Volz, T, Lütgehetmann, M, Giersch, K, Bornscheuer, T, Lohse, AW, Petersen, J, Ma, H, Klumpp, K, Fletcher, SP & Dandri, M 2014, 'Immune cell responses are not required to induce substantial hepatitis B virus antigen decline during pegylated interferon-alpha administration', J HEPATOL, vol. 60, no. 3, pp. 500-7. https://doi.org/10.1016/j.jhep.2013.10.021

APA

Allweiss, L., Volz, T., Lütgehetmann, M., Giersch, K., Bornscheuer, T., Lohse, A. W., Petersen, J., Ma, H., Klumpp, K., Fletcher, S. P., & Dandri, M. (2014). Immune cell responses are not required to induce substantial hepatitis B virus antigen decline during pegylated interferon-alpha administration. J HEPATOL, 60(3), 500-7. https://doi.org/10.1016/j.jhep.2013.10.021

Vancouver

Allweiss L, Volz T, Lütgehetmann M, Giersch K, Bornscheuer T, Lohse AW et al. Immune cell responses are not required to induce substantial hepatitis B virus antigen decline during pegylated interferon-alpha administration. J HEPATOL. 2014 Mar 1;60(3):500-7. https://doi.org/10.1016/j.jhep.2013.10.021

Bibtex

@article{be1d6db3b4df47c2bb129d252bd40416,
title = "Immune cell responses are not required to induce substantial hepatitis B virus antigen decline during pegylated interferon-alpha administration",
abstract = "BACKGROUND & AIMS: Pegylated interferon-alpha (PegIFNα) remains an attractive treatment option for chronic hepatitis B virus (HBV) infection because it induces higher rates of antigen loss and seroconversion than treatment with polymerase inhibitors. Although early HBsAg decline is recognised as the best predictor of sustained response to IFN-based therapy, it is unclear whether immune cell functions are required to induce significant antigenemia reduction in the first weeks of treatment. Aim of the study was to investigate whether PegIFNα can induce sustained human hepatocyte responsiveness and substantial loss of circulating and intrahepatic viral antigen loads in a system lacking immune cell functions.METHODS: HBV-infected humanized uPA/SCID mice received either PegIFNα, entecavir (ETV), or both agents in combination. Serological and intrahepatic changes were determined by qRT-PCR and immunohistochemistry and compared to untreated mice.RESULTS: After 4 weeks of treatment, median viremia reduction was greater in mice treated with ETV (either with or without PegIFNα) than with PegIFNα. In contrast, levels of circulating HBeAg, HBsAg, and intrahepatic HBcAg were significantly reduced (p = 0.03) only in mice receiving PegIFNα alone or in combination, as compared to mice receiving ETV monotherapy. Progressive antigen reduction was also demonstrated in mice receiving PegIFNα for 12 weeks (HBeAg = Δ1log; HBsAg = Δ1.4log; p < 0.0001). Notably, repeated administrations of the longer-active PegIFNα could breach the impairment of HBV-infected hepatocyte responsiveness and induce sustained enhancement of human interferon stimulated genes (ISG).CONCLUSIONS: The antiviral effects of PegIFNα exerted on the human hepatocytes can induce sustained responsiveness and trigger substantial HBV antigen decline without claiming the involvement of immune cell responses.",
author = "Lena Allweiss and Tassilo Volz and Marc L{\"u}tgehetmann and Katja Giersch and Till Bornscheuer and Lohse, {Ansgar W} and Joerg Petersen and Han Ma and Klaus Klumpp and Fletcher, {Simon P} and Maura Dandri",
note = "Copyright {\textcopyright} 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.",
year = "2014",
month = mar,
day = "1",
doi = "10.1016/j.jhep.2013.10.021",
language = "English",
volume = "60",
pages = "500--7",
journal = "J HEPATOL",
issn = "0168-8278",
publisher = "Elsevier",
number = "3",

}

RIS

TY - JOUR

T1 - Immune cell responses are not required to induce substantial hepatitis B virus antigen decline during pegylated interferon-alpha administration

AU - Allweiss, Lena

AU - Volz, Tassilo

AU - Lütgehetmann, Marc

AU - Giersch, Katja

AU - Bornscheuer, Till

AU - Lohse, Ansgar W

AU - Petersen, Joerg

AU - Ma, Han

AU - Klumpp, Klaus

AU - Fletcher, Simon P

AU - Dandri, Maura

N1 - Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

PY - 2014/3/1

Y1 - 2014/3/1

N2 - BACKGROUND & AIMS: Pegylated interferon-alpha (PegIFNα) remains an attractive treatment option for chronic hepatitis B virus (HBV) infection because it induces higher rates of antigen loss and seroconversion than treatment with polymerase inhibitors. Although early HBsAg decline is recognised as the best predictor of sustained response to IFN-based therapy, it is unclear whether immune cell functions are required to induce significant antigenemia reduction in the first weeks of treatment. Aim of the study was to investigate whether PegIFNα can induce sustained human hepatocyte responsiveness and substantial loss of circulating and intrahepatic viral antigen loads in a system lacking immune cell functions.METHODS: HBV-infected humanized uPA/SCID mice received either PegIFNα, entecavir (ETV), or both agents in combination. Serological and intrahepatic changes were determined by qRT-PCR and immunohistochemistry and compared to untreated mice.RESULTS: After 4 weeks of treatment, median viremia reduction was greater in mice treated with ETV (either with or without PegIFNα) than with PegIFNα. In contrast, levels of circulating HBeAg, HBsAg, and intrahepatic HBcAg were significantly reduced (p = 0.03) only in mice receiving PegIFNα alone or in combination, as compared to mice receiving ETV monotherapy. Progressive antigen reduction was also demonstrated in mice receiving PegIFNα for 12 weeks (HBeAg = Δ1log; HBsAg = Δ1.4log; p < 0.0001). Notably, repeated administrations of the longer-active PegIFNα could breach the impairment of HBV-infected hepatocyte responsiveness and induce sustained enhancement of human interferon stimulated genes (ISG).CONCLUSIONS: The antiviral effects of PegIFNα exerted on the human hepatocytes can induce sustained responsiveness and trigger substantial HBV antigen decline without claiming the involvement of immune cell responses.

AB - BACKGROUND & AIMS: Pegylated interferon-alpha (PegIFNα) remains an attractive treatment option for chronic hepatitis B virus (HBV) infection because it induces higher rates of antigen loss and seroconversion than treatment with polymerase inhibitors. Although early HBsAg decline is recognised as the best predictor of sustained response to IFN-based therapy, it is unclear whether immune cell functions are required to induce significant antigenemia reduction in the first weeks of treatment. Aim of the study was to investigate whether PegIFNα can induce sustained human hepatocyte responsiveness and substantial loss of circulating and intrahepatic viral antigen loads in a system lacking immune cell functions.METHODS: HBV-infected humanized uPA/SCID mice received either PegIFNα, entecavir (ETV), or both agents in combination. Serological and intrahepatic changes were determined by qRT-PCR and immunohistochemistry and compared to untreated mice.RESULTS: After 4 weeks of treatment, median viremia reduction was greater in mice treated with ETV (either with or without PegIFNα) than with PegIFNα. In contrast, levels of circulating HBeAg, HBsAg, and intrahepatic HBcAg were significantly reduced (p = 0.03) only in mice receiving PegIFNα alone or in combination, as compared to mice receiving ETV monotherapy. Progressive antigen reduction was also demonstrated in mice receiving PegIFNα for 12 weeks (HBeAg = Δ1log; HBsAg = Δ1.4log; p < 0.0001). Notably, repeated administrations of the longer-active PegIFNα could breach the impairment of HBV-infected hepatocyte responsiveness and induce sustained enhancement of human interferon stimulated genes (ISG).CONCLUSIONS: The antiviral effects of PegIFNα exerted on the human hepatocytes can induce sustained responsiveness and trigger substantial HBV antigen decline without claiming the involvement of immune cell responses.

U2 - 10.1016/j.jhep.2013.10.021

DO - 10.1016/j.jhep.2013.10.021

M3 - SCORING: Journal article

C2 - 24398036

VL - 60

SP - 500

EP - 507

JO - J HEPATOL

JF - J HEPATOL

SN - 0168-8278

IS - 3

ER -