End-of-treatment HBsAg, HBcrAg and HBV RNA predict the risk of off-treatment ALT flares in chronic hepatitis B patients
Copyright © 2022. Published by Elsevier B.V..
BACKGROUND/PURPOSE(S): Since ALT flares after therapy withdrawal are associated with adverse outcomes, risk stratification is of major importance. We aimed to study whether off-treatment flares are related with virological outcomes, and if serum levels of novel biomarkers at end-of-treatment (EOT) can predict flares.
METHODS: Chronic hepatitis B patients who participated in three global randomised trials of peginterferon-based therapy were studied (99-01, PARC, ARES). HBV RNA, HBsAg and HBcrAg were quantified at EOT. Associations between EOT biomarker levels and flares were assessed as continuous data and after categorisation. Flares were defined as ALT ≥5xULN during six months after therapy cessation.
RESULTS: We included 344 patients; 230 HBeAg-positive and 114 HBeAg-negative. Patients were predominantly Caucasian (77.0%) and had genotype A/B/C/D in 23.3/7.3/13.4/52.3%. Flares were observed in 122 patients (35.5%). Flares were associated with lower rates of sustained response (3.5% vs 26.8% among patients with and without a flare; p < 0.001). Higher HBsAg (OR 1.586, 95%CI 1.231-2.043), HBV RNA (OR 1.695, 95%CI 1.371-2.094) and HBcrAg (OR 1.518, 95%CI 1.324-1.740) levels were associated with higher risk of flares (p < 0.001). Combinations of biomarkers further improved risk stratification, especially HBsAg + HBV RNA. Findings were consistent in multivariate analysis adjusted for potential predictors including HBeAg-status and EOT-response (HBV DNA <200 IU/mL).
CONCLUSION: Off-treatment ALT flares were not associated with favourable virological outcomes. Higher EOT serum HBsAg, HBcrAg and HBV RNA were associated with a higher risk of flares after therapy withdrawal. These findings can be used to guide decision-making regarding therapy discontinuation and off-treatment follow-up.
TRIAL REGISTRATION: ClinicalTrials.gov: NCT00114361, NCT00146705, NCT00877760.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:56 |
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| Enthalten in: |
Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi - 56(2023), 1 vom: 13. Feb., Seite 31-39 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Brakenhoff, Sylvia M [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 09.02.2023 Date Revised 09.02.2023 published: Print-Electronic ClinicalTrials.gov: NCT00114361, NCT00877760, NCT00146705 Citation Status MEDLINE |
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| doi: |
10.1016/j.jmii.2022.06.002 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM344605027 |
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| 041 | |a eng | ||
| 100 | 1 | |a Brakenhoff, Sylvia M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a End-of-treatment HBsAg, HBcrAg and HBV RNA predict the risk of off-treatment ALT flares in chronic hepatitis B patients |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 09.02.2023 | ||
| 500 | |a Date Revised 09.02.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT00114361, NCT00877760, NCT00146705 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022. Published by Elsevier B.V. | ||
| 520 | |a BACKGROUND/PURPOSE(S): Since ALT flares after therapy withdrawal are associated with adverse outcomes, risk stratification is of major importance. We aimed to study whether off-treatment flares are related with virological outcomes, and if serum levels of novel biomarkers at end-of-treatment (EOT) can predict flares | ||
| 520 | |a METHODS: Chronic hepatitis B patients who participated in three global randomised trials of peginterferon-based therapy were studied (99-01, PARC, ARES). HBV RNA, HBsAg and HBcrAg were quantified at EOT. Associations between EOT biomarker levels and flares were assessed as continuous data and after categorisation. Flares were defined as ALT ≥5xULN during six months after therapy cessation | ||
| 520 | |a RESULTS: We included 344 patients; 230 HBeAg-positive and 114 HBeAg-negative. Patients were predominantly Caucasian (77.0%) and had genotype A/B/C/D in 23.3/7.3/13.4/52.3%. Flares were observed in 122 patients (35.5%). Flares were associated with lower rates of sustained response (3.5% vs 26.8% among patients with and without a flare; p < 0.001). Higher HBsAg (OR 1.586, 95%CI 1.231-2.043), HBV RNA (OR 1.695, 95%CI 1.371-2.094) and HBcrAg (OR 1.518, 95%CI 1.324-1.740) levels were associated with higher risk of flares (p < 0.001). Combinations of biomarkers further improved risk stratification, especially HBsAg + HBV RNA. Findings were consistent in multivariate analysis adjusted for potential predictors including HBeAg-status and EOT-response (HBV DNA <200 IU/mL) | ||
| 520 | |a CONCLUSION: Off-treatment ALT flares were not associated with favourable virological outcomes. Higher EOT serum HBsAg, HBcrAg and HBV RNA were associated with a higher risk of flares after therapy withdrawal. These findings can be used to guide decision-making regarding therapy discontinuation and off-treatment follow-up | ||
| 520 | |a TRIAL REGISTRATION: ClinicalTrials.gov: NCT00114361, NCT00146705, NCT00877760 | ||
| 650 | 4 | |a Clinical Trial | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Flare | |
| 650 | 4 | |a HBV | |
| 650 | 4 | |a Hepatitis B virus | |
| 650 | 4 | |a Hepatology | |
| 650 | 4 | |a Liver | |
| 650 | 4 | |a Serum biomarkers | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a DNA, Viral |2 NLM | |
| 650 | 7 | |a Hepatitis B Core Antigens |2 NLM | |
| 650 | 7 | |a Hepatitis B e Antigens |2 NLM | |
| 650 | 7 | |a Hepatitis B Surface Antigens |2 NLM | |
| 650 | 7 | |a RNA |2 NLM | |
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| 700 | 1 | |a de Knegt, Robert J |e verfasserin |4 aut | |
| 700 | 1 | |a van Campenhout, Margo J H |e verfasserin |4 aut | |
| 700 | 1 | |a van der Eijk, Annemiek A |e verfasserin |4 aut | |
| 700 | 1 | |a Brouwer, Willem P |e verfasserin |4 aut | |
| 700 | 1 | |a van Bömmel, Florian |e verfasserin |4 aut | |
| 700 | 1 | |a Boonstra, André |e verfasserin |4 aut | |
| 700 | 1 | |a Hansen, Bettina E |e verfasserin |4 aut | |
| 700 | 1 | |a Berg, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Janssen, Harry L A |e verfasserin |4 aut | |
| 700 | 1 | |a de Man, Robert A |e verfasserin |4 aut | |
| 700 | 1 | |a Sonneveld, Milan J |e verfasserin |4 aut | |
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