Predicting Early Viral Control under Direct-Acting Antiviral Therapy for Chronic Hepatitis C Virus Using Pretreatment Immunological Markers
Recent introduction of all-oral direct-acting antiviral (DAA) treatment has revolutionized care of patients with chronic hepatitis C virus (HCV) infection. Regrettably, the high cost of DAA treatment is burdensome for healthcare systems and may be prohibitive for some patients who would otherwise be...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-02-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00146/full |
| _version_ | 1818137310784389120 |
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| author | James A. Hutchinson Kilian Weigand Akinbami Adenugba Katharina Kronenberg Jan Haarer Florian Zeman Paloma Riquelme Matthias Hornung Norbert Ahrens Hans J. Schlitt Edward K. Geissler Jens M. Werner |
| author_facet | James A. Hutchinson Kilian Weigand Akinbami Adenugba Katharina Kronenberg Jan Haarer Florian Zeman Paloma Riquelme Matthias Hornung Norbert Ahrens Hans J. Schlitt Edward K. Geissler Jens M. Werner |
| author_sort | James A. Hutchinson |
| collection | DOAJ |
| description | Recent introduction of all-oral direct-acting antiviral (DAA) treatment has revolutionized care of patients with chronic hepatitis C virus (HCV) infection. Regrettably, the high cost of DAA treatment is burdensome for healthcare systems and may be prohibitive for some patients who would otherwise benefit. Understanding how patient-related factors influence individual responses to DAA treatment may lead to more efficient prescribing. In this observational study, patients with chronic HCV infection were comprehensively monitored by flow cytometry to identify pretreatment immunological variables that predicted HCV RNA negativity within 4 weeks of commencing DAA treatment. Twenty-three patients [genotype 1a (n = 10), 1b (n = 9), and 3 (n = 4)] were treated with daclatasvir plus sofosbuvir (SOF) (n = 15), ledipasvir plus SOF (n = 4), or ritonavir-boosted paritaprevir, ombitasvir, and dasabuvir (n = 4). DAA treatment most prominently altered the distribution of CD8+ memory T cell subsets. Knowing only pretreatment frequencies of CD3+ and naive CD8+ T cells allowed correct classification of 83% of patients as “fast” (HCV RNA-negative by 4 weeks) or “slow” responders. In a prospective cohort, these parameters correctly classified 90% of patients. Slow responders exhibited higher frequencies of CD3+ T cells, CD8+ TEM cells, and CD5high CD27− CD57+ CD8+ chronically activated T cells, which is attributed to bystander hyperactivation of virus-non-specific CD8+ T cells. Taken together, non-specific, systemic CD8+ T cell activation predicted a longer time to viral clearance. This discovery allows pretreatment identification of individuals who may not require a full 12-week course of DAA therapy; in turn, this could lead to individualized prescribing and more efficient resource allocation. |
| first_indexed | 2024-12-11T09:54:16Z |
| format | Article |
| id | doaj.art-09c9fb1214c64dc787b44b09fb5e722b |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T09:54:16Z |
| publishDate | 2018-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-09c9fb1214c64dc787b44b09fb5e722b2022-12-22T01:12:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-02-01910.3389/fimmu.2018.00146323670Predicting Early Viral Control under Direct-Acting Antiviral Therapy for Chronic Hepatitis C Virus Using Pretreatment Immunological MarkersJames A. Hutchinson0Kilian Weigand1Akinbami Adenugba2Katharina Kronenberg3Jan Haarer4Florian Zeman5Paloma Riquelme6Matthias Hornung7Norbert Ahrens8Hans J. Schlitt9Edward K. Geissler10Jens M. Werner11Department of Surgery, University Hospital Regensburg, Regensburg, GermanyDepartment of Internal Medicine I, University Hospital Regensburg, Regensburg, GermanyDepartment of Surgery, University Hospital Regensburg, Regensburg, GermanyDepartment of Surgery, University Hospital Regensburg, Regensburg, GermanyDepartment of Surgery, University Hospital Regensburg, Regensburg, GermanyCenter for Clinical Studies, University Hospital Regensburg, Regensburg, GermanyDepartment of Surgery, University Hospital Regensburg, Regensburg, GermanyDepartment of Surgery, University Hospital Regensburg, Regensburg, GermanyDepartment of Transfusion Medicine, University Hospital Regensburg, Regensburg, GermanyDepartment of Surgery, University Hospital Regensburg, Regensburg, GermanyDepartment of Surgery, University Hospital Regensburg, Regensburg, GermanyDepartment of Surgery, University Hospital Regensburg, Regensburg, GermanyRecent introduction of all-oral direct-acting antiviral (DAA) treatment has revolutionized care of patients with chronic hepatitis C virus (HCV) infection. Regrettably, the high cost of DAA treatment is burdensome for healthcare systems and may be prohibitive for some patients who would otherwise benefit. Understanding how patient-related factors influence individual responses to DAA treatment may lead to more efficient prescribing. In this observational study, patients with chronic HCV infection were comprehensively monitored by flow cytometry to identify pretreatment immunological variables that predicted HCV RNA negativity within 4 weeks of commencing DAA treatment. Twenty-three patients [genotype 1a (n = 10), 1b (n = 9), and 3 (n = 4)] were treated with daclatasvir plus sofosbuvir (SOF) (n = 15), ledipasvir plus SOF (n = 4), or ritonavir-boosted paritaprevir, ombitasvir, and dasabuvir (n = 4). DAA treatment most prominently altered the distribution of CD8+ memory T cell subsets. Knowing only pretreatment frequencies of CD3+ and naive CD8+ T cells allowed correct classification of 83% of patients as “fast” (HCV RNA-negative by 4 weeks) or “slow” responders. In a prospective cohort, these parameters correctly classified 90% of patients. Slow responders exhibited higher frequencies of CD3+ T cells, CD8+ TEM cells, and CD5high CD27− CD57+ CD8+ chronically activated T cells, which is attributed to bystander hyperactivation of virus-non-specific CD8+ T cells. Taken together, non-specific, systemic CD8+ T cell activation predicted a longer time to viral clearance. This discovery allows pretreatment identification of individuals who may not require a full 12-week course of DAA therapy; in turn, this could lead to individualized prescribing and more efficient resource allocation.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00146/fullhepatitis C virusdirect-acting antiviral therapyimmune monitoringbiomarkermemory T cellnon-classical monocyte |
| spellingShingle | James A. Hutchinson Kilian Weigand Akinbami Adenugba Katharina Kronenberg Jan Haarer Florian Zeman Paloma Riquelme Matthias Hornung Norbert Ahrens Hans J. Schlitt Edward K. Geissler Jens M. Werner Predicting Early Viral Control under Direct-Acting Antiviral Therapy for Chronic Hepatitis C Virus Using Pretreatment Immunological Markers Frontiers in Immunology hepatitis C virus direct-acting antiviral therapy immune monitoring biomarker memory T cell non-classical monocyte |
| title | Predicting Early Viral Control under Direct-Acting Antiviral Therapy for Chronic Hepatitis C Virus Using Pretreatment Immunological Markers |
| title_full | Predicting Early Viral Control under Direct-Acting Antiviral Therapy for Chronic Hepatitis C Virus Using Pretreatment Immunological Markers |
| title_fullStr | Predicting Early Viral Control under Direct-Acting Antiviral Therapy for Chronic Hepatitis C Virus Using Pretreatment Immunological Markers |
| title_full_unstemmed | Predicting Early Viral Control under Direct-Acting Antiviral Therapy for Chronic Hepatitis C Virus Using Pretreatment Immunological Markers |
| title_short | Predicting Early Viral Control under Direct-Acting Antiviral Therapy for Chronic Hepatitis C Virus Using Pretreatment Immunological Markers |
| title_sort | predicting early viral control under direct acting antiviral therapy for chronic hepatitis c virus using pretreatment immunological markers |
| topic | hepatitis C virus direct-acting antiviral therapy immune monitoring biomarker memory T cell non-classical monocyte |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00146/full |
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