Genetic variation near interleukin 28B and the risk of hepatocellular carcinoma in patients with chronic hepatitis C
Genetic variation near interleukin 28B and the risk of hepatocellular carcinoma in patients with chronic hepatitis C
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DOI：
10.1007/s00535-013-0858-2
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发表时间：
2014-07-01
影响因子：
6.3
通讯作者：
Izumi, Namiki
中科院分区：
文献类型：
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作者：
Asahina, Yasuhiro;Tsuchiya, Kaoru;Izumi, Namiki
为探讨白细胞介素28 B（interleukin 28 B，IL 28 B）基因单核苷酸多态性（single nucleotide polymorphism，SNP）与肝细胞癌（hepatocellular carcinoma，HCC）的关系，对792例接受干扰素治疗的慢性丙型肝炎患者进行了队列研究。测定rs 8099917和rs 12979860处的SNP。在平均4.9年的随访期内，通过Kaplan-Meier和考克斯比例风险分析对累积发病率和HCC风险进行分析。在已知感染时间的这些患者中确定纤维化进展率（FPR）（n = 294）Js 8099917 nonTT（次要纯合子或杂合子）患者中的累积HCC发病率显著高于rs 8099917 TT（主要纯合子）患者（10年内20.8%对10.5%，logrank检验，p = 0.002）。这种差异在基因型1感染的患者和用聚乙二醇干扰素和利巴韦林治疗的患者中是显著的。在nonSVR中，干扰素在抑制nonTT患者的丙氨酸氨基转移酶（ALT）和/或甲胎蛋白（AFP）水平方面的作用有限。干扰素治疗后这些数值的抑制与HCC的发生率降低相关。FPR在TT和nonTT患者中相似。rs 8099917 nonTT与HCV基因型1患者和接受聚乙二醇干扰素和利巴韦林治疗的患者中更高的HCC发展相关。在非TT患者中观察到的较高的HCC发病率部分是由于这些患者中干扰素对ALT和/或AFP的抑制有限。
We aimed to clarify the association between single nucleotide polymorphism (SNP) located near interleukin 28B and hepatocellular carcinoma (HCC).A cohort comprising 792 patients treated with interferon for chronic hepatitis C was investigated. SNPs at rs8099917 and rs12979860 were determined. Cumulative incidence and HCC risk were analyzed by Kaplan-Meier and Cox proportional hazard analyses for a mean follow-up period of 4.9 years. Fibrosis progression rate (FPR) was determined in these patients with a known time of infection (n = 294).Cumulative HCC incidence was significantly higher in rs8099917 nonTT (minor homozygote or heterozygote) patients than in rs8099917 TT (major homozygote) patients (20.8 vs. 10.5 % over 10 years, logrank test, p = 0.002). This difference was notable in patients infected with genotype 1 and those treated with pegylated interferon and ribavirin. Among nonSVRs, interferon had a limited effect in suppressing alanine aminotransferase (ALT) and/or alpha-fetoprotein (AFP) levels in nonTT patients. The suppression of these values after interferon therapy was associated with a lower incidence of HCC. FPR were similar in TT and nonTT patients.rs8099917 nonTT is related to higher HCC development in patients with HCV genotype 1 and those treated with pegylated interferon and ribavirin. Higher HCC incidence observed in nonTT patients partly results from the limited suppression of ALT and/or AFP by interferon in these patients.