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Role of IL28B genotyping in patients with hepatitis C virus-associated mixed cryoglobulinemia and response to PEG-IFN and ribavirin treatment

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Abstract

The role of interleukin (IL) 28B in the treatment of chronic hepatitis C (CHC) has recently been examined in many studies, while a possible relationship between IL28B and the presence of mixed cryoglobulinemia (MC) remains to be clarified. In this study, we analyzed the influence of IL28B rs8099917/rs12979860 on the presence of MC and the role in treatment with PEG-IFN. We retrospectively examined 541 patients affected by CHC who were treated with pegylated interferon (PEG-IFN) and ribavirin from 2003 to 2012. We included all treatment-naïve patients without other viral co-infections or major contraindications to the PEG-IFN and ribavirin standard of care. One hundred seventy-five patients (32.3 %) had MC; 49 of these (33.3 %) had symptomatic MC. The IL28B rs8099917/rs12979860 TT/CC genotype was the most frequent in MC-positive patients with sustained virological response (SVR) (p < 0.001), while the TG/TC genotype was most frequent in non-SVR (p < 0.001). The TT/CC genotype was found to be the main positive predictive factor of MC in HCV patients (OR = 11.914; IQR = 7.092-18.776; p < 0.001); HCV genotype 2/3 was the strongest positive predictive factor of SVR (OR = 10.448; IQR = 8.352-21.561; p < 0.001); IL28B rs8099917/rs12979860 TT/CC was a better predictive factor than rs12979860 CC alone (OR = 9.829 vs. 2.663). Negative predictive factors were Metavir score F3-F4 (OR = 0.625; IQR = 0.416-0.779; p = 0.008), insulin-resistance (OR = 0.315; IQR = 0.224-0.585; p < 0.001) and presence of symptoms (OR = 0.716; IQR = 0.492-0.855; p < 0.001). IL28B rs8099917/rs12979860 is useful in the treatment of MC-positive HCV patients with PEG-IFN and ribavirin; the TT/CC genotype is associated with SVR, the TG/TC with non-SVR; TT/CC is also predictive of MC in HCV patients.

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Abbreviations

HCV:

Hepatitis C virus

HCV-4:

Hepatitis C virus genotype 4

MC:

Mixed cryoglobulinemia

PEG-IFN:

Pegylated interferon alfa

SVR:

Sustained virological response

RVR:

Rapid virological response

EVR:

Early virological response

SNP:

Single nucleotide polymorphism

IL:

Interleukin

NR:

Null responder

IR:

Insulin resistance

PR:

Partial responder

REL:

Relapser

IQR:

Inter-quartile range

SD:

Standard deviation

DAAs:

Directly acting antivirals

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Funding

This study was not supported.

Conflict of interest

All authors declare that they have no conflicts of interest.

Ethical approval

This study was approved by our local ethics committee (“HCV-GEN”, 28/7/14, no. 0012710).

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Authors and Affiliations

  1. Unit of Infectious Diseases, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, Turin, Italy

    Lucio Boglione, Jessica Cusato, Sarah Allegra, Giuseppe Cariti, Giovanni Di Perri & Antonio D’Avolio

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  1. Lucio Boglione
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  2. Jessica Cusato
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  3. Sarah Allegra
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  4. Giuseppe Cariti
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  6. Antonio D’Avolio
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Correspondence to Lucio Boglione.

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Boglione, L., Cusato, J., Allegra, S. et al. Role of IL28B genotyping in patients with hepatitis C virus-associated mixed cryoglobulinemia and response to PEG-IFN and ribavirin treatment. Arch Virol 160, 2009–2017 (2015). https://doi.org/10.1007/s00705-015-2482-3

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  • DOI: https://doi.org/10.1007/s00705-015-2482-3

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