Hutchinson, James A. and Weigand, Kilian and Adenugba, Akinbami and Kronenberg, Katharina and Haarer, Jan and Zeman, Florian and Riquelme, Paloma and Hornung, Matthias and Ahrens, Norbert and Schlitt, Hans J. and Geissler, Edward K. and Werner, Jens M. (2018) Predicting Early Viral Control under Direct-Acting Antiviral Therapy for Chronic Hepatitis C Virus Using Pretreatment Immunological Markers. FRONTIERS IN IMMUNOLOGY, 9: 146. ISSN 1664-3224,
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SAMPLE-SIZE; hepatitis C virus; direct-acting antiviral therapy; immune monitoring; biomarker; memory T cell; non-classical monocyte; classifier |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin Medicine > Zentren des Universitätsklinikums Regensburg > Zentrum für Klinische Studien |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 19 Mar 2020 12:34 |
| Last Modified: | 19 Mar 2020 12:34 |
| URI: | https://pred.uni-regensburg.de/id/eprint/15055 |
Actions (login required)
 |
View Item |
