Peripheral blood correlates of virologic relapse after Sofosbuvir and Ribavirin treatment of Genotype-1 HCV infection
Autor: | Shyam Kottilil, Wenjie Xu, Eric G. Meissner, Cody Orr, Henry Masur |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Male
0301 basic medicine medicine.medical_specialty Genotype Sofosbuvir Neutrophils T-Lymphocytes Hepatitis C virus Hepacivirus medicine.disease_cause Antiviral Agents Virus lcsh:Infectious and parasitic diseases 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Medical microbiology Gene expression analysis Recurrence Interferon Ribavirin medicine Humans lcsh:RC109-216 Longitudinal Studies Relapse Whole blood Sustained virologic response business.industry Hepatitis C Chronic Killer Cells Natural Gene expression profiling Treatment Outcome 030104 developmental biology Infectious Diseases chemistry Immunology Drug Therapy Combination Female 030211 gastroenterology & hepatology Direct acting antiviral Interferons Transcriptome business Research Article medicine.drug |
Zdroj: | BMC Infectious Diseases, Vol 20, Iss 1, Pp 1-9 (2020) BMC Infectious Diseases |
ISSN: | 1471-2334 |
Popis: | Background Treatment of chronic hepatitis C virus infection with direct acting antiviral therapy results in viral elimination in over 90% of cases. The duration of treatment required to achieve cure differs between individuals and relapse can occur. We asked whether cellular and transcriptional profiling of peripheral blood collected during treatment could identify biomarkers predictive of treatment outcome. Methods We analyzed peripheral blood collected during treatment of genotype 1 HCV with 24 weeks of sofosbuvir and weight-based or low dose ribavirin in a trial in which 29% of patients relapsed. Changes in host immunity during treatment were assessed by flow cytometry and whole blood gene expression profiling. Differences in expression of immune-relevant transcripts based on treatment outcome were analyzed using the Nanostring Human Immunology V2 panel. Results Multiple cellular populations changed during treatment, but pre-treatment neutrophil counts were lower and natural post-treatment killer cell counts were higher in patients who relapsed. Pre-treatment expression of genes associated with interferon-signaling, T-cell dysfunction, and T-cell co-stimulation differed by treatment outcome. We identified a pre- and post-treatment gene expression signature with high predictive capacity for distinguishing treatment outcome, but neither signature was sufficiently robust to suggest viability for clinical use. Conclusions Patients who relapse after hepatitis C virus therapy differ immunologically from non-relapsers based on expression of transcripts related to interferon signaling and T-cell dysfunction, as well as by peripheral neutrophil and NK-cell concentrations. These data provide insight into the host immunologic basis of relapse after DAA therapy for HCV and suggests mechanisms which may be relevant for understanding outcomes with currently approved regimens. |
Databáze: | OpenAIRE |
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