宿主白介素28B基因多态性与慢性丙型肝炎抗病毒疗效的研究分析

徐辉; 郭丽琳; 何伶俐等

宿主白介素28B基因多态性与慢性丙型肝炎抗病毒疗效的研究分析

Association of Interleukin 28B Polymorphisms with Response to Pegylatedinterferon Plus Ribavirin Therapy for Chronic Hepatitis C

摘要

摘要: 【摘要】目的分析我国四川地区慢性丙型肝炎(丙肝)患者白介素28B(IL28B) rs12979860位点基因多态性的特点，并探讨其对聚乙二醇化干扰素(PEG-IFN)联合利巴韦林(RBV)治疗慢性丙肝的疗效的预测价值。方法对56例慢性丙肝患者进行PEG-IFN α-2a联合RBV治疗48周, 治疗结束随访24周, 同时对宿主IL28B rs12979860位点进行基因测序，分别分析不同IL28B基因多态性、丙肝病毒(HCV)的基因型、基线病毒载量患者的慢性丙肝抗病毒治疗疗效。结果 56例慢性丙肝患者的IL28B rs12979860位点基因型以CC型为主，占76.8%(43/56)，CT型占23.2%(13/56)，未发现TT型。患者性别、年龄、体质量、感染时间、治疗前基线谷丙转氨酶(ALT)水平、基线HCV RNA载量以及感染的HCV基因型在不同IL28B rs12979860位点基因型间的差异均没有统计学意义（P>0.05）。PEG-IFN联合RBV治疗慢性丙肝疗效显著，其持续病毒学应答（SVR）率可达82.1％。CC型患者的SVR率高于CT型（90.7% vs. 53.8%， P=0.009）。高病毒载量组（≥6×105 IU/mL）与低载量组（＜6×105 IU/mL）的SVR率分别为79.5％和88.2％，差异无统计学意义（P=0.684）；感染HCV基因1型和非基因1型组的患者SVR率分别为76.9%和92.9%，差异无统计学意义(P=0.363)。但是在高病毒载量组和感染HCV基因1型组的患者中， CC型患者的SVR率仍高于CT型（87.5% vs. 42.9%， P=0.033； 89.7% vs. 50.0%， P=0.025）。结论我国四川地区慢性丙肝患者的IL28B rs12979860位点基因型以CC型为主，CC型患者抗HCV疗效优于CT型，宿主IL28B的基因型较HCV的基因型以及基线病毒载量对疗效的预测更有价值。

Abstract: 【Abstract】 Objective To investigate the characteristics of gene polymorphisms at rs12979860 of interleukin 28B (IL28B) and explore the relationships between the genetic polymorphisms and the antiviral therapy efficiency for chronic hepatitis C patients in the Sichuan region of China.Methods Data from 56 patients treated for 48 weeks with PEG-IFN α-2a plus weight-based Ribavirin (RBV), which were followed for 24 weeks after the end of treatment, were analyzed. And the IL28B rs12979860 genotype was detected by polymerase chain reaction- restriction techniques (PCR) and sequencing analysis. Results Two genotypes, CC (76.8%) and CT (23.2%), were identified in the study. There are no significant correlation in sex, age, body weight, routes of infection, baseline ALT value, baseline viral load and hepatitis C viral (HCV) genotype between the patients with CC genotype and CT genotype (P>0.05). PEG-IFN α-2a plus RBV showed a conspicuous therapeutic effect in patients of the Sichuan region of China, and the rate of sustained virological response (SVR) was 82.1% (46/56). The higher rates of SVR were observed in patients with IL28B genotype CC than genotype CT (90.7% versus 53.8%,P=0.009). Statistically higher proportion of SVR wasn’t observed in patients with lower baseline viral load (＜6×105 IU/mL) 〔88.2% versus 79.5% in patients with higher baseline viral load (≥6×105 IU/mL), P=0.684〕 and statistically lower proportion of SVR wasn’t observed in patients infected with HCV genotype 1 (76.9％ versus 92.9％ in patients infected with HCV genotype non-1, P=0.363). The higher rates of SVR were observed in patients with IL28B genotype CC than patients with genotype CT in the group of higher baseline viral load (≥6×105 IU/mL) (87.5％ versus 42.9％, P=0.033) and in HCV genotype 1 infected patients (89.7％ versus 50.0％, CM(154.5mmP=0.025). Conclusion CC genotype was accounted for the majority at rs12979860 in patients of the Sichuan region of China. The higher rates of SVR were observed in IL28B genotype CC than genotype CT. Compared to HCV viral genotype and baseline viral load, IL28B genotype may predict the treatment effect of greater value.

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