The Dynamic Relationship between Innate Immune Biomarkers and Interferon-Based Treatment Effects and Outcome in Hepatitis C Virus Infection Is Altered by Telaprevir

Soluble CD14 (sCD14) and IL-18 are markers and mediators of the innate immune response, and their plasma levels candidate biomarkers of HCV treatment effects and outcome. Here, we retrospectively studied sCD14 and IL-18 over the course of interferon-based treatment of HCV genotype 1 infection, with...

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Vydáno v:	PloS one Ročník 9; číslo 8; s. e105665
Hlavní autoři:	Malone, David F. G., Falconer, Karolin, Weiland, Ola, Sandberg, Johan K.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Public Library of Science 28.08.2014 Public Library of Science (PLoS)
Témata:	Activation Adult Aged Aged, 80 and over Analysis Antiviral agents Antiviral Agents - pharmacology Antiviral Agents - therapeutic use Antiviral drugs Apoptosis Biological markers Biological response modifiers Biology and Life Sciences Biomarkers Biomarkers - blood Biopsy Care and treatment CD14 antigen Consent Cytokines Drug Therapy, Combination Female Gene expression Genotype & phenotype Genotypes Health aspects Hepatitis Hepatitis C Hepatitis C - blood Hepatitis C - drug therapy Hepatitis C - immunology Hepatitis C virus HIV Hospitals Human immunodeficiency virus Humans Immune response Immune system Immunity, Innate - drug effects Infection Infections Infectious diseases Innate immunity Interferon Interferons - therapeutic use Interleukin 18 Interleukin-18 - blood Lipopolysaccharide Receptors - blood Liver diseases Male Medicine Medicine and health sciences Middle Aged Oligopeptides - therapeutic use Patients Plasma levels Retrospective Studies Ribavirin Ribavirin - pharmacology Ribavirin - therapeutic use Serine Proteinase Inhibitors - pharmacology Serine Proteinase Inhibitors - therapeutic use Statistical analysis Therapy Treatment Outcome Viral infections Viruses Young Adult Sweden
ISSN:	1932-6203, 1932-6203
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Shrnutí:	Soluble CD14 (sCD14) and IL-18 are markers and mediators of the innate immune response, and their plasma levels candidate biomarkers of HCV treatment effects and outcome. Here, we retrospectively studied sCD14 and IL-18 over the course of interferon-based treatment of HCV genotype 1 infection, with the aim to investigate the impact of direct-acting antivirals (DAAs) on the dynamics and relationships between these biomarkers and treatment effects and outcome. Two cohorts were followed longitudinally; one treated with standard dual therapy of pegylated IFNα and ribavirin, and one cohort receiving triple therapy including Telaprevir. sCD14 and IL-18 were measured before and during treatment and analyzed in relation to treatment effects. The initial analysis confirmed two patterns previously observed in patients with HCV/HIV-1 co-infection: Baseline levels of sCD14 were significantly lower in patients that went on to clear HCV infection in response to IFNα and ribavirin, and sCD14 levels were strongly induced during the course of this treatment. Interestingly, baseline levels of sCD14 and IL-18 in combination predicted treatment outcome in dual therapy better than either marker alone. Notably, these associations were weaker with the addition of Telaprevir to the treatment regimen, suggesting that the relationships between innate immune activation and outcome were altered and diminished by inclusion of a DAA in the treatment. In triple therapy, the dynamic increase of sCD14 in response to treatment was higher in patients clearing the virus, suggesting that the innate response to interferon is still significantly associated with outcome in patients treated with DAA-containing regimens. These results support the notion that levels of innate immune activation before and during treatment are associated with interferon-based treatment outcome. Furthermore, the addition of Telaprevir significantly alters the dynamics and relationships between innate immune biomarkers and treatment effects and outcome.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Competing Interests: The authors have declared that no competing interests exist. Conceived and designed the experiments: DFGM KF JKS. Performed the experiments: DFGM. Analyzed the data: DFGM JKS. Contributed reagents/materials/analysis tools: KF OW. Contributed to the writing of the manuscript: DFGM KF OW JKS.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0105665