Bellanti Francesco, Lauletta Gianfranco, Villani Rosanna, Lipsi Maria Rosaria, Natalicchio Maria Iole, Sansonno Domenico, Vendemiale Gianluigi, Serviddio Gaetano
From the Department of Medical and Surgical Sciences, C.U.R.E. Centre for Liver Diseases Research and Treatment, Institute of Internal Medicine, University of Foggia, Foggia, Italy (FB, RV, GV, GS); Liver Unit, Division of Internal Medicine and Clinical Oncology, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari, Italy (GL, DS); and Department of Clinical Pathology, II Laboratory, Section of Cytogenetic and Molecular Biology, University Hospital "Ospedali Riuniti", Foggia, Italy (MRL, MIN).
Medicine (Baltimore). 2015 Sep;94(35):e1409. doi: 10.1097/MD.0000000000001409.
Chronic hepatitis C is commonly associated with extrahepatic manifestations. Cryoglobulins are observed in 40% to 60% of such patients and their presence seems to modify response to therapy. The new antivirals are greatly improving the sustained virological response (SVR); however, their high cost limits the use, leaving pegylated interferon plus ribavirin (PR) still the standard-of-care therapy worldwide. Since PR therapy is burdened with several side effects, pretreatment predictions of patients who are unlikely to respond to this regimen may avoid ineffective treatment. Variants of the interleukin-28B (IL28B) gene correlate with an SVR to PR, and combined IL28B polymorphisms may improve the prediction of treatment outcome.The potential role of both rs8099917 and rs12979860 IL28B single nucleotide polymorphisms (SNPs) combined with presence of cryoglobulins in predicting SVR to PR in hepatitis C virus (HCV)-chronically infected patients was analyzed in the present study.Single and combined IL28B SNPs (rs12979860 and rs8099917) were analyzed in 64 chronic HCV patients treated with PR showing circulating cryoglobulins and compared to 108 noncryoglobulinemic subjects to verify the predictive value on the SVR.The association of rs12979860CC or rs8099917TT with SVR was confirmed in the noncryoglobulinemic group but not in cryoglobulinemic patients. Moreover, the combined determination of both SNPs improved the prediction of SVR in noncryoglobulinemic patients but not in the cryoglobulinemic subgroup.We report that both single and combined determination of IL28B rs12979860 and rs8099917 SNPs in chronic HCV patients with circulating cryoglobulins treated with PR may have a reduced predictive value of SVR.
慢性丙型肝炎常伴有肝外表现。40%至60%的此类患者可检测到冷球蛋白，其存在似乎会改变对治疗的反应。新型抗病毒药物正在极大地提高持续病毒学应答（SVR）；然而，其高昂的成本限制了使用，聚乙二醇干扰素联合利巴韦林（PR）仍是全球标准的治疗方案。由于PR治疗存在多种副作用，对不太可能对该方案有反应的患者进行治疗前预测可避免无效治疗。白细胞介素-28B（IL28B）基因的变异与PR治疗的SVR相关，联合的IL28B多态性可能会改善治疗结果的预测。本研究分析了rs8099917和rs12979860这两个IL28B单核苷酸多态性（SNP）以及冷球蛋白的存在对慢性丙型肝炎病毒（HCV）感染患者PR治疗SVR的预测作用。对64例接受PR治疗且有循环冷球蛋白的慢性HCV患者的单个及联合IL28B SNP（rs12979860和rs8099917）进行分析，并与108例无冷球蛋白血症的受试者进行比较，以验证其对SVR的预测价值。在无冷球蛋白血症组中，rs12979860CC或rs8099917TT与SVR的关联得到证实，但在有冷球蛋白血症的患者中未得到证实。此外，联合检测这两个SNP可改善无冷球蛋白血症患者SVR的预测，但在有冷球蛋白血症的亚组中未改善。我们报告，在接受PR治疗且有循环冷球蛋白的慢性HCV患者中，单个及联合检测IL28B rs12979860和rs8099917 SNP对SVR的预测价值可能会降低。
