title: Role of IL28B genotyping in patients with hepatitis C virus-associated mixed cryoglobulinemia and response to PEG-IFN and ribavirin treatment.
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.
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, Turin, Italy, lucio.boglione@unito.it.
authors.forename: Lucio
authors.initials: L
authors.lastname: Boglione
authors.forename: Jessica
authors.initials: J
authors.lastname: Cusato
authors.forename: Sarah
authors.initials: S
authors.lastname: Allegra
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cariti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Perri
authors.forename: Antonio
authors.initials: A
authors.lastname: D'Avolio
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D003449:Cryoglobulinemia / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a