不同HCV基因型感染的慢性丙型肝炎和肝硬化患者对重组人干扰素α-2a治疗应答的影响

doi:10.3969/j.issn.1672-5069.2021.06.033

摘要/Abstract

摘要： 目的研究丙型肝炎病毒(HCV)基因型对慢性丙型肝炎(CHC)和丙型肝炎肝硬化患者接受干扰素α-2a治疗的影响。方法 2015年1月～2020年4月我院收治的CHC患者198例和丙型肝炎肝硬化患者200例,均接受肝活检和干扰素α-2a治疗24 周,随访24周。采用实时荧光定量PCR法检测血清HCV RNA水平,采用基因序列测定法检测HCV基因分型,采用单因素和多因素回归分析影响治疗应答的因素。结果肝硬化组HCV基因1b型检出率为31.0%,显著高于86例≤S1的15.1%或112例S2～3组的18.8%(P<0.05);212例无应答组HCV基因1b型检出率显著高于186例治疗应答组(29.7%对17.7%),1a型检出率显著低于治疗应答组(17.9%对28.0%,P<0.05);应答组早期应答率为60.8%,显著高于无应答组的18.9%(P<0.05),应答组治疗前血清HCV RNA高水平比率为37.1%,显著低于无应答组的47.6%(P<0.05);HCV基因1b型(OR为0.553,95%CI为0.316～0.969)是影响干扰素治疗应答的危险因素,而早期应答(OR为1.704,95%CI为1.008～2.881)为影响干扰素治疗应答的保护因素。结论 HCV基因型可影响干扰素α-2a治疗慢性HCV感染者的应答反应,检测病毒基因型可能对选择合适的治疗方案或疗程有指导意义。

关键词: 肝硬化, 慢性丙型肝炎, 干扰素α-2a, 丙型肝炎病毒基因型, 治疗应答

Abstract: Objective The aim of this clinical trial was to investigate the impact of HCV genotypes on the treatment response of recombinant human interferon α-2a (IFN-α-2a) in patients with chronic hepatitis C (CHC) and hepatitis C liver cirrhosis. Methods A total of 198 patients with CHC and 200 patients with hepatitis C-induced liver cirrhosis were enrolled in our hospital between January 2015 and April 2020, and all received liver biopsies and IFN-α-2a treatment for 24 weeks and followed-up for 24 weeks. Serum HCV RNA loads were detected by Roche's lightcycle real-time fluorescent quantitative PCR and the HCV genotypes were detected by gene sequencing. The liver injuries were evaluated by Knodell histological activity index scoring systems. The factors impacting response to IFN-α-2a therapy was analyzed by univariate or multivariate regression analysis. Results The percentage of HCV 1b genotype in patients with liver cirrhosis was 31.0%, significantly higher than 15.1% in 86 CHC patients with less than S1 liver fibrosis or 18.8%(P<0.05) in 112 CHC patients with S2-3 liver fibrosis; the percentage of HCV 1b genotype in 212 patients without response to IFN-α-2a therapy was significantly higher than(29.7% vs. 17.7%), and the percentage of genotype 1a was significantly lower than (17.9% vs. 28.0%, P<0.05) in 186 responders; the early virological response rate in responders was 60.8%, significantly higher than 18.9%(P<0.05), and high serum HCV RNA loads was 37.1%, significantly lower than 47.6%(P<0.05) in non-responders; the HCV 1b genotype (OR:0.553, 95%CI:0.316-0.969) was the independent risk factor, while the early response (OR:1.704, 95%CI:1.008-2.881) was the protective factor for response to IFN-α-2a therapy. Conclusion The detection of HCV genotype could predict the response to IFN-α-2a therapy in patients with CHC and CHC-induced liver cirrhosis, which might guide the selection of antiviral therapy strategy and the treatment period.

Key words: Liver cirrhosis, Hepatitis C, Hepatitis C virus genotypes, Interferon-α-2a, Response

束青华, 张楠楠, 葛勇胜. 不同HCV基因型感染的慢性丙型肝炎和肝硬化患者对重组人干扰素α-2a治疗应答的影响[J]. 实用肝脏病杂志, 2021, 24(6): 899-902.

Shu Qinghua, Zhang Nannan, Ge Yongsheng. Impact of HCV genotypes on the treatment response of recombinant human interferon α-2a in patients with chronic hepatitis C and hepatitis C liver cirrhosis[J]. Journal of Practical Hepatology, 2021, 24(6): 899-902.

参考文献

[1]娜丽.慢性丙型肝炎患者外周血IL-28B基因型多态性及其对持续病毒学应答的影响.实用肝脏病杂志,2017,20(5):600-601.
[2]Ibrahim AM, Ahmed HS, Alazizi NM, et al.Glutathione S-transferase M1 and T1 gene polymorphisms and the outcome of chronic hepatitis C virus infection in Egyptian patients.Ann Hum Genet, 2016, 80(1):32-37.
[3]凡豪志,张云,岳明,等.CC趋化因子细胞受体5基因多态性与慢性丙肝干扰素疗效关联性的研究.中华疾病控制杂志,2018,22(10):1020-1023.
[4]中华医学会肝病学分会和感染病学分会.《丙型肝炎防治指南》2019年更新版.实用肝脏病杂志,2020,23(1):S33-52.
[5]Sultanik P, Kramer L, Soudan D, et al.The relationship between liver stiffness measurement and outcome in patients with chronic hepatitis C and cirrhosis: a retrospective longitudinal hospital study.Aliment Pharmacol Ther, 2016, 44(5):505-513.
[6]刘亿军,段舒馨,游春芳,等.HFE基因多态性检测判断慢性丙型肝炎患者疾病活动的价值.实用肝脏病杂志,2020,23(2):49-52.
[7]Vallet-Pichard A, Sultanik P, Meritet J F, et al.SAT-427 - The relationship between FIB-4 index variations and outcome in patients with chronic hepatitis C and cirrhosis: comparison with liver stiffness measurement.J Hepatol, 2016, 64(2):715-717.
[8]潘美民,李文娟,蒋芳清,等.慢性丙型肝炎患者血清IL-17A,FGF和IL-7水平与丙型肝炎病毒感染自发清除临床意义探讨.实用肝脏病杂志,2019,22(6):840-843.
[9]Echeverría N, Chiodi D, López P, et al.IL28B gene polymorphism rs12979860, but not rs8099917, contributes to the occurrence of chronic HCV infection in Uruguayan patients.Virol J, 2018, 15(1):40-45.
[10] Jacobson IM, Lim JK, Fried MW.American Gastroenterological Association Institute Clinical practice update-expert review: Care of patients who have achieved a sustained virologic response after antiviral therapy for chronic hepatitis C infection. Gastroenterology, 2017, 152(6):1578-1587.
[11] da Silva FR, Guimares-Vasconcelos AC, de-Carvalho-França LF, et al. Relationship between -889 C/T polymorphism in interleukin-1A gene and risk of chronic periodontitis: Evidence from a meta-analysis with new published findings.Med Oral Patol OralCir Bucal, 2017, 22(1):7-14.
[12] Pouryasin M, Keshvari M, Sharafi H, et al.The ITPA and c20orf194 polymorphisms and hematological changes during treatment with pegylated-interferon plus ribavirin in patients with chronic hepatitis C. Hepat Mon, 2016, 16(2):35278.
[13] 史昌河,宋秀云,魏阳,等.青岛地区宿主IL-28B基因多态性及HCV基因型对慢性丙型肝炎抗病毒疗效的影响.中华实验和临床感染病杂志(电子版),2017,11(1):45-50.
[14] Sun Y, Qi H. Relationship between the 308GA polymorphism of the tumor necrosis factor alpha gene and acute or chronic pancreatitis: a meta-analysis.Asian biomedicine, 2017, 6(1):1-7.
[15] De Souza MMT, Vaisberg VV, Abreu RM, et al.UGT1A1*28 relationship with abnormal total bilirubin levels in chronic hepatitis C patients: Outcomes from a case-control study.Medicine(Baltimore), 2017, 96(11):6306-6309.
[16] He XT, Xu HQ, Wang XM, et al.Association between polymorphisms of the APOBEC3G gene and chronic hepatitis B viral infection and hepatitis B virus-related hepatocellular carcinoma.World J Gastroenterol, 2017, 23(2):232-241.
[17] 巫晶晶,黄鹏,岳明,等.TNFRSF11A和TNFRSF11B基因多态性与HCV感染转归的关系.中华流行病学杂志,2019,40(10):1291-1295.
[18] Yücel O, Güne H, Yücel H, et al.Association between multidrug resistance-1 C3435T gene polymorphism and right ventricular dysfunction in patients with chronic obstructive pulmonary disease: cross-sectional study.Sao Paulo Med J, 2018, 136(2):140-143.
[19] Santos JC, de Deus DM, de Moura IM, et al.Association between the IFNA1 (-2C→T) polymorphism and increased IFNAR1 gene expression levels in chronic hepatitis B infection.Intervirology, 2015, 58(6):393-402.
[20] Bogdanovi Z, Marinovi-Terzi I, Kuret S, et al.The impact of IL-6 and IL-28B gene polymorphisms on treatment outcome of chronic hepatitis C infection among intravenous drug users in Croatia.Peerj, 2016, 4(10):2576-2579.
[21] Coppola N, Rosa Z, Cirillo G, et al.TM6SF2 E167K variant is associated with severe steatosis in chronic hepatitis C, regardless of PNPLA3 polymorphism.Liver Int, 2015, 35(8):1959-1963.
[22] 刘立明,毛远丽,王海滨,等.白介素28B 基因多态性与慢性丙型肝炎患者抗病毒疗效的相关性研究.中华检验医学杂志,2015,38(3):155-158.
[23] PhuengwasS, Hongtrakul V, Hirankarn N, et al.IFNAR1 gene polymorphism associated with chronic hepatitis B virus infection in a Thai population. Enceasia, 2015, 41(1):393-403.