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
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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