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Abstract
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 2.9×, IQR: 1.7–12.4 vs 1.2×, IQR: 0.5–1.8; (P=0.01) IFNG 7.3×, IQR: 1.7–32.6 vs 0.7×, IQR: 0.4–1.3; P=0.002 and USP18 3.7×, IQR: 2.1–7.7 vs 1.4×, 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.
Supplementary material
Figure S1 USP18 expression in non-SVR patients, fold difference in comparison with healthy controls.
Abbreviations: BT, breakthrough; NR, non-response; REL, relapse; non-SVR, treatment failure (non-response, relapse, breakthrough).
Acknowledgments
The study was supported by the grant of Internal Grant Agency of Ministry of Health of the Czech Republic (No NT/11235-5).
Disclosure
The authors report no conflicts of interest in this work.