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Immunological biomarkers as indicators for outcome after discontinuation of nucleos(t)ide analogue therapy in patients with HBeAg negative chronic hepatitis B

Immunological biomarkers as indicators for outcome after discontinuation of nucleos(t)ide analogue therapy in patients with HBeAg negative chronic hepatitis B
Immunological biomarkers as indicators for outcome after discontinuation of nucleos(t)ide analogue therapy in patients with HBeAg negative chronic hepatitis B
The optimal duration of treatment with nucleos(t)ide analogues (NAs) for patients with HBeAg‐negative Chronic Hepatitis B (CHB) is unknown. The aim of this study was to identify an immune signature associated with off‐treatment remission to NA therapy. We performed microarray analysis of PBMCs from six patients with chronic hepatitis B who stopped NA therapy (3 with off‐treatment remission, 3 with relapse) and 5 patients with chronic HBV infection (previously termed “inactive carriers”) served as controls. Results were validated using qRT‐PCR on a second group of 21 individuals (17 patients who stopped treatment and 4 controls). PBMCs from 38 patients on long‐term NA treatment were analysed for potential to stop treatment.

Microarray analysis indicated that patients with off‐treatment remission segregated as a distinct out‐group. Twenty‐one genes were selected for subsequent validation. Ten of these were expressed at significantly lower levels in the patients with off‐treatment remission compared to the patients with relapse and predicted remission with AUC of 0.78‐0.92. IFNγ, IL‐8, FASLG and CCL4 were the most significant by logistic regression. Twelve (31.6%) of 38 patients on long‐term NA therapy had expression levels of all these four genes below cut‐off values, and hence were candidates for stopping treatment. Our data suggest that patients with HBeAg‐negative CHB who remain in off‐treatment remission 3 years after NA cessation have a distinct immune signature and that PBMC RNA levels of IFNγ, IL‐8, FASLG and CCL4 may serve as potential biomarkers for stopping NA therapy.
1352-0504
Kranidioti, Hariklia
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Manolakopoulos, Spilios
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Kontos, George
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Breen, Michael S.
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Kourikou, Anastasia
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Deutsch, Melanie
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Quesada Del Bosque, Maria
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Martinez-Nunez, Rocio
a6069f08-55cf-4477-b895-9c4fdd2ee5ee
Naiyer, Mohammed M
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Woelk, Christopher H
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Sanchez-Elsner, Tilman
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Hadziyannis, Emilia
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Papatheodoridis, George
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Khakoo, Salim
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Kranidioti, Hariklia
67c560b5-240b-4445-88fd-69bee09e1570
Manolakopoulos, Spilios
6142cc46-9179-44ed-a562-46e19357a97a
Kontos, George
2e17550e-9ade-4cfa-8abc-714a352f0369
Breen, Michael S.
2a4241cd-4f16-4f7f-9165-1459ed2c8890
Kourikou, Anastasia
f8038421-88c0-49a1-9446-41bf948e5a2a
Deutsch, Melanie
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Quesada Del Bosque, Maria
9e01196a-6eec-45fd-8822-4ee4b7527c0f
Martinez-Nunez, Rocio
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Naiyer, Mohammed M
b4ac5546-4f7d-462c-9632-a60a552ea3b3
Woelk, Christopher H
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Sanchez-Elsner, Tilman
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Hadziyannis, Emilia
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Papatheodoridis, George
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Khakoo, Salim
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Kranidioti, Hariklia, Manolakopoulos, Spilios, Kontos, George, Breen, Michael S., Kourikou, Anastasia, Deutsch, Melanie, Quesada Del Bosque, Maria, Martinez-Nunez, Rocio, Naiyer, Mohammed M, Woelk, Christopher H, Sanchez-Elsner, Tilman, Hadziyannis, Emilia, Papatheodoridis, George and Khakoo, Salim (2019) Immunological biomarkers as indicators for outcome after discontinuation of nucleos(t)ide analogue therapy in patients with HBeAg negative chronic hepatitis B. Journal of Viral Hepatitis. (doi:10.1111/jvh.13068).

Record type: Article

Abstract

The optimal duration of treatment with nucleos(t)ide analogues (NAs) for patients with HBeAg‐negative Chronic Hepatitis B (CHB) is unknown. The aim of this study was to identify an immune signature associated with off‐treatment remission to NA therapy. We performed microarray analysis of PBMCs from six patients with chronic hepatitis B who stopped NA therapy (3 with off‐treatment remission, 3 with relapse) and 5 patients with chronic HBV infection (previously termed “inactive carriers”) served as controls. Results were validated using qRT‐PCR on a second group of 21 individuals (17 patients who stopped treatment and 4 controls). PBMCs from 38 patients on long‐term NA treatment were analysed for potential to stop treatment.

Microarray analysis indicated that patients with off‐treatment remission segregated as a distinct out‐group. Twenty‐one genes were selected for subsequent validation. Ten of these were expressed at significantly lower levels in the patients with off‐treatment remission compared to the patients with relapse and predicted remission with AUC of 0.78‐0.92. IFNγ, IL‐8, FASLG and CCL4 were the most significant by logistic regression. Twelve (31.6%) of 38 patients on long‐term NA therapy had expression levels of all these four genes below cut‐off values, and hence were candidates for stopping treatment. Our data suggest that patients with HBeAg‐negative CHB who remain in off‐treatment remission 3 years after NA cessation have a distinct immune signature and that PBMC RNA levels of IFNγ, IL‐8, FASLG and CCL4 may serve as potential biomarkers for stopping NA therapy.

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Kranidioti_et_al-2019-Journal_of_Viral_Hepatitis (1) - Accepted Manuscript
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Accepted/In Press date: 9 January 2019
e-pub ahead of print date: 31 January 2019

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Local EPrints ID: 428208
URI: https://eprints.soton.ac.uk/id/eprint/428208
ISSN: 1352-0504
PURE UUID: 9085110d-688b-4975-86f9-b675e6ee6a27
ORCID for Mohammed M Naiyer: ORCID iD orcid.org/0000-0002-4441-311X

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Date deposited: 15 Feb 2019 17:30
Last modified: 08 Apr 2019 16:30

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Contributors

Author: Hariklia Kranidioti
Author: Spilios Manolakopoulos
Author: George Kontos
Author: Michael S. Breen
Author: Anastasia Kourikou
Author: Melanie Deutsch
Author: Maria Quesada Del Bosque
Author: Rocio Martinez-Nunez
Author: Mohammed M Naiyer ORCID iD
Author: Emilia Hadziyannis
Author: George Papatheodoridis
Author: Salim Khakoo

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