浙江省湖州地区白细胞介素-28B单核苷酸多态性与丙型肝炎病毒自发清除和抗病毒疗效的关系

Relationship between interleukin-28B single nucleotide polymorphism and spontaneous clearance and antiviral efficacy of hepatitis C virus infection in Huzhou area of Zhejiang Province

目的分析浙江省湖州地区丙型肝炎病毒(hepatitis C virus, HCV)感染患者的白细胞介素(interleukin, IL)-28B rs8099917位点单核苷酸多态性与HCV感染的自发清除和抗病毒疗效之间的关系.方法对所有268例HCV感染患者基线水平进行HCV RNA低拷贝定量、基因型、IL-28B rs8099917位点单核苷酸多态性基因检测. 163例慢性丙型肝炎患者完成聚乙二醇干扰素联合利巴韦林( PR方案)抗病毒治疗48周,随访24周;44例患者给予达拉他韦联合索磷布韦抗病毒治疗12周.监测不同IL-28B rs8099917位点基因型患者抗病毒治疗后的病毒学应答情况.计数资料采用χ^2 检验比较.结果268例患者IL-28B rs8099917位点基因型以TT型为主,占84.33%,GT型占15.67%,没有发现GG 型.135例急性 HCV 感染者中有61 例发生病毒自发清除,74 例转为慢性感染,自发清除率 TT 型占47.11%,GT型占28.57%,TT型与GT型的自发清除率差异无统计学意义(χ^2 =1.072,P=0.30).完成PR治疗的163例慢性丙型肝炎患者,治疗结束后24周持续病毒学应答( sustained virological response , SVR)率为86.50%(141例),TT型的SVR率优于GT型(91.67%比47.36%),差异有统计学意义(χ^2 =28.212,P<0.05).基因1b型与基因2a型对24周 SVR率的影响差异无统计学意义(χ^2 =1.525, P>0.05).44例给予达拉他韦联合索磷布韦抗病毒治疗的患者中,TT型和GT型患者治疗结束后24 周SVR率均为100%.结论浙江省湖州地区HCV感染患者的IL-28B rs8099917位点多态性与急性HCV自发清除无明显相关性. PR治疗慢性丙型肝炎中TT型患者的SVR率优于GT型,具有预测价值.达拉他韦联合索磷布韦抗病毒治疗SVR率可达100%.

Objective To analyze the effect of single nucleotide polymorphism (SNP) rs8099917 of interleukin-28B (IL-28B) on spontaneous virus clearance and the efficacy of antiviral therapy in hepatitis C virus (HCV) infected patients in Huzhou area of Zhejiang Province. Methods A total of 268 HCV-infected patients were enrolled. The high sensitive HCV RNA quantification, HCV genotype and the IL-28B rs8099917 SNP were detected at baseline. One hundred and sixty-three patients received pegylated interferon α-2a (Peg-IFNα-2a) and ribavirin (RBV) combined antiviral therapy (referred as PR treatment) for 48 weeks, who were followed up for 24 weeks. The remaining 44 patients were treated with sofosbuvir and daclatasvir for 12 weeks. The virological response of patients with different IL-28B rs8099917 genotypes was monitored. The count data was compared by χ^2 test. Results The distributions of IL-28B rs8099917 SNP were 84.33% for TT genotype and 15.67% for GT genotype, while the GG genotype was not detected. Of the 135 patients with acute HCV infection, 61 cases had spontaneous viral clearance, 74 cases were converted to chronic infection. The spontaneous clearance rates were 47.11% for TT genotype and 28.57% for GT genotype. There was no significant difference of the spontaneous clearance rate between TT and GT genotype (χ^2=1.072, P=0.30). In 163 chronic hepatitis C (CHC) patients with PR treatment, the rate of sustained virological response (SVR) after 24 weeks follow-up was 86.50%(141 cases). SVR rate in patients with TT genotype was significantly higher than those with GT genotype (91.67% vs 47.36%,χ^2=28.212, P<0.05). There was no statistically significant difference of the SVR rates between genotype 1b and 2a (χ^2=1.525, P>0.05). In 44 patients received sofosbuvir and daclatasvir treatment, both SVR rates of TT genotype and GT genotype were 100%. Conclusions In Huzhou area of Zhejiang Province, there is no significant correlation between IL-28B rs8099917 genotype and spontaneous clearance in patients with acute HCV infection, but the genotype of IL-28B rs8099917 is valuable for the prediction of PR treatment efficacy, the SVR rate of the TT genotype is superior to the GT genotype. The SVR rate can reach 100% in patients received combination therapy of sofosbuvir and daclatasvir independent of polymorphism of IL-28B.