USP18 downregulation in peripheral blood mononuclear cells predicts nonresponse to interferon-based triple therapy in patients with chronic hepatitis C, genotype I: a pilot study

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F15%3A00059655" target="_blank" >RIV/00023001:_____/15:00059655 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.dovepress.com/usp18-downregulation-in-peripheral-blood-mononuclear-cells-predicts-no-peer-reviewed-article-TCRM" target="_blank" >https://www.dovepress.com/usp18-downregulation-in-peripheral-blood-mononuclear-cells-predicts-no-peer-reviewed-article-TCRM</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.2147/TCRM.S94010" target="_blank" >10.2147/TCRM.S94010</a>

Jazyk výsledku

angličtina

Název v původním jazyce

USP18 downregulation in peripheral blood mononuclear cells predicts nonresponse to interferon-based triple therapy in patients with chronic hepatitis C, genotype I: a pilot study

Popis výsledku v původním jazyce

Background and aims: Patients with advanced liver fibrosis owing to chronic hepatitis C virus genotype 1 represent a difficult-to-treat group even if a protease inhibitor is added to pegylated interferon alpha and ribavirin. Therefore, only patients with a high chance of cure should be treated with interferon-based treatment. Patients and methods: Expression of IFNG, IFNLR1, and interferon-sensitive genes CXCL9, IFI16, IFI27, ISG15, and USP18 in peripheral blood mononuclear cells was assessed before and during the initial 12 weeks of treatment. The studied group consisted of 26 treatment-experienced patients of average age of 50 years with advanced liver fibrosis compared to seven healthy volunteers. Fourteen patients were treated with pegylated interferon alpha 2b, ribavirin, and boceprevir and 12 patients with telaprevir. The overall sustained virological response (SVR) rate was 69% (18/26). Results: A significant difference in the initial expression (median, interquartile range [IQR]) of CXCL9 2.9x, IQR: 1.7-12.4 vs 1.2x, IQR: 0.5-1.8; (P=0.01) IFNG 7.3x, IQR: 1.7-32.6 vs 0.7x, IQR: 0.4-1.3; P=0.002 and USP18 3.7x, IQR: 2.1-7.7 vs 1.4x, IQR: 0.9-1.6; (P=0.03) was found between the SVR and non-SVR groups. Expression of all analyzed genes was progressively increasing during the first 12 weeks of therapy, but a significant difference between SVR and non-SVR group was found only in USP18 expression at week 12 (P=0.001). Initial expression of four genes predicted SVR in univariate analysis (CXCL9 [OR: 12.00, 95% CI: 1.21-118.89], IFI27 [OR: 12.00, 95% CI: 1.21-118.89], IFNG [OR: 10.50, 95% CI: 1.50-73.67], USP18 [OR: 21.00, 95% CI: 2.05-215.18]). In multivariate analysis, only the initial expression of USP18 was identified as a predictor of SVR (P=0.047). Conclusion: Initial expression of USP18 and the course of its activation could be a reliable predictor of SVR achievement.

Název v anglickém jazyce

USP18 downregulation in peripheral blood mononuclear cells predicts nonresponse to interferon-based triple therapy in patients with chronic hepatitis C, genotype I: a pilot study

Popis výsledku anglicky

Background and aims: Patients with advanced liver fibrosis owing to chronic hepatitis C virus genotype 1 represent a difficult-to-treat group even if a protease inhibitor is added to pegylated interferon alpha and ribavirin. Therefore, only patients with a high chance of cure should be treated with interferon-based treatment. Patients and methods: Expression of IFNG, IFNLR1, and interferon-sensitive genes CXCL9, IFI16, IFI27, ISG15, and USP18 in peripheral blood mononuclear cells was assessed before and during the initial 12 weeks of treatment. The studied group consisted of 26 treatment-experienced patients of average age of 50 years with advanced liver fibrosis compared to seven healthy volunteers. Fourteen patients were treated with pegylated interferon alpha 2b, ribavirin, and boceprevir and 12 patients with telaprevir. The overall sustained virological response (SVR) rate was 69% (18/26). Results: A significant difference in the initial expression (median, interquartile range [IQR]) of CXCL9 2.9x, IQR: 1.7-12.4 vs 1.2x, IQR: 0.5-1.8; (P=0.01) IFNG 7.3x, IQR: 1.7-32.6 vs 0.7x, IQR: 0.4-1.3; P=0.002 and USP18 3.7x, IQR: 2.1-7.7 vs 1.4x, IQR: 0.9-1.6; (P=0.03) was found between the SVR and non-SVR groups. Expression of all analyzed genes was progressively increasing during the first 12 weeks of therapy, but a significant difference between SVR and non-SVR group was found only in USP18 expression at week 12 (P=0.001). Initial expression of four genes predicted SVR in univariate analysis (CXCL9 [OR: 12.00, 95% CI: 1.21-118.89], IFI27 [OR: 12.00, 95% CI: 1.21-118.89], IFNG [OR: 10.50, 95% CI: 1.50-73.67], USP18 [OR: 21.00, 95% CI: 2.05-215.18]). In multivariate analysis, only the initial expression of USP18 was identified as a predictor of SVR (P=0.047). Conclusion: Initial expression of USP18 and the course of its activation could be a reliable predictor of SVR achievement.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FP - Ostatní lékařské obory

OECD FORD obor

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Projekt

<a href="/cs/project/NT11235" target="_blank" >NT11235: Úloha faktorů hostitele v odpovědi na protivirovou léčbu chronické hepatitidy C</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2015

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Therapeutics and Clinical Risk Management

ISSN

1178-203X

e-ISSN

—

Svazek periodika

11

Číslo periodika v rámci svazku

Nov 23

Stát vydavatele periodika

NZ - Nový Zéland

Počet stran výsledku

9

Strana od-do

1853-1861

Kód UT WoS článku

000366562400001

EID výsledku v databázi Scopus

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