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中华实验和临床感染病杂志(电子版) ›› 2018, Vol. 12 ›› Issue (02) : 145 -149. doi: 10.3877/cma.j.issn.1674-1358.2018.02.009

所属专题: 文献

临床论著

国产聚乙二醇化重组集成干扰素变异体联合利巴韦林治疗慢性丙型病毒性肝炎患者甲状腺功能异常及其对疗效的影响
邓莉平1, 韦芳菲1, 熊勇1,(), 高世成1, 张永喜1   
  1. 1. 430071 武汉市,武汉大学中南医院感染科
  • 收稿日期:2017-07-12 出版日期:2018-04-15
  • 通信作者: 熊勇
  • 基金资助:
    湖北省自然科学基金(No. 2013CFB254)

Incidence of thyroid dysfunction during pegylated recombinant interferon variant and ribavirin combined treatment in patients with chronic hepatitis C and the impact on anti-HCV treatment

Liping Deng1, Fangfei Wei1, Yong Xiong1,(), Shicheng Gao1, Yongxi Zhang1   

  1. 1. Department of Infectious Diseases, Zhongnan Hospital, Wuhan University, Wuhan 430071, China
  • Received:2017-07-12 Published:2018-04-15
  • Corresponding author: Yong Xiong
  • About author:
    Corresponding author: Xiong Yong, Email:
引用本文:

邓莉平, 韦芳菲, 熊勇, 高世成, 张永喜. 国产聚乙二醇化重组集成干扰素变异体联合利巴韦林治疗慢性丙型病毒性肝炎患者甲状腺功能异常及其对疗效的影响[J]. 中华实验和临床感染病杂志(电子版), 2018, 12(02): 145-149.

Liping Deng, Fangfei Wei, Yong Xiong, Shicheng Gao, Yongxi Zhang. Incidence of thyroid dysfunction during pegylated recombinant interferon variant and ribavirin combined treatment in patients with chronic hepatitis C and the impact on anti-HCV treatment[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2018, 12(02): 145-149.

目的

观察国产聚乙二醇化重组集成干扰素变异体注射液(PegIFN-SA)联合利巴韦林(RBV)治疗慢性丙型病毒性肝炎(CHC)患者时甲状腺功能异常(TD)或甲状腺自身抗体(TAs)产生情况及对疗效影响。

方法

前瞻性观察2013年9月至2015年12月于本中心接受国产PegIFN-SA联合RBV治疗的CHC病例45例。试验组患者给予PegIFN-SA皮下注射(1.5 μg/kg、1次/周),对照组患者给予聚乙二醇化干扰素α-2a(PegIFN-α-2a)皮下注射(派罗欣180 μg、1次/周),两组患者均联合口服利巴韦林(000~1 200 mg/d),HCV基因2、3型患者治疗24周,非HCV基因2、3型患者治疗48周,停药后均随访6个月。在治疗前、治疗后每3个月及停药后6个月监测两组患者甲状腺功能及HCV RNA水平。

结果

试验组慢性丙型肝炎患者30例,其中男性14例,女性16例,平均年龄为(36.5 ± 12.0)岁(19~56岁),HCV基因2、3型患者6例,HCV非基因2、3型患者24例。治疗结束停药半年后HCV持续应答率为83.3%(25/30),共13例患者出现TD或TAs,其发生率为43.3%(13/30);9例发生TD患者中4例(44.4%)丙型肝炎复发,高于未出现TD者(1/21,4.8%),差异具有统计学意义(P = 0.02)。

结论

国产PegIFN-SA联合RBV治疗慢性丙型病毒性肝炎患者甲状腺功能异常及抗体阳性较为常见,发生甲状腺功能异常者CHC更易复发。

Objective

To investigate the incidence and long-term outcomes of thyroid dysfunction (TD) in patients with chronic hepatitis C (CHC) who received pegylated recombinant interferon variant combined with ribavirin (PegIFN-SA/RBV) treatment.

Methods

Total of 45 patients with CHC admitted in Wuhan University Zhongnan Hospital during September 2013 and December 2015 were collected. Patients in test group were treated with PegIFN-SA subcutaneous injection once a week (1.5 μg/kg). Patients in control group were treated with PegIFN α-2a for subcutaneous injection once a week (180 μg). All patients were also treated with oral RBV (1 000-1 200 mg/d) .The patients with HCV genotype 2/3 were treated for 24 weeks, the other patients with no-genotype 2/3 HCV were treated for 48 weeks, all patients were followed up for 24 weeks after treatment. Thyroid function and HCV RNA were measured at baseline, every 3 months during therapy and 6 months after treatment.

Results

Among the 30 patients who completed treatment with PegIFN-SA/RBV and 24 weeks follow-up, 14 cases were males and the median age was (36.5 ± 12.0) years old (19-56 years old), 6 cases were with HCV genotype 2/3, 83.3% (25/30) cases achieved sustained virological response (SVR); 13 (43.3%, 13/30) patients developed TD/TAs during the PegIFN-SA/RBV treatment. The relapse rate of HCV was higher in patients with TD than those without TD (44.4% vs. 4.8%, P = 0.02).

Conclusions

The development of TD/TAs was common in patients with CHC receiving Peg-IFN-SA/RBV treatment. TD is associated with an unfavorable virological response to PegIFN-SA/RBV.

[1]
Mizokami M, Yokosuka O, Takehara T, et al. Ledipasvir and sofosbuvir fixed-dose combination with and without ribavirin for 12 weeks in treatment-naive and previously treated Japanese patients with genotype 1 hepatitis C: an open-label, randomised, phase 3 trial[J]. Lancet Infect Dis,2015,15(6):645-653.
[2]
孙艳伏, 刘畅, 王长华, 等. 聚乙二醇化重组集成干扰素变异体治疗丙肝患者致精神不良反应的临床观察与心理干预[J]. 中华现代护理杂志2013,19(17):2005-2007.
[3]
中华医学会内分泌学分会《中国甲状腺疾病诊治指南》编写组. 中国甲状腺疾病诊治指南--甲状腺功能亢进症[J]. 中华内科杂志,2007,46(10):876-882.
[4]
中华医学会内分泌学分会《中国甲状腺疾病诊治指南》编写组. 甲状腺疾病诊治指南--甲状腺功能减退症[J]. 中华内科杂志,2007,46(11):967-971.
[5]
Mandac JC, Chaudhry S, Sherman KE, et al. The clinical and physiological spectrum of interferon-alpha induced thyroiditis: toward a new classification[J]. Hepatology,2006,43(4):661-672.
[6]
中华医学会肝病学分会, 感染病学分会. 丙型肝炎防治指南(2015更新版)[J]. 中华临床感染病杂志,2015,8(6):504-525.
[7]
陈新月, 尚佳, 杨锐峰, 等. 难治性慢性丙型肝炎初治患者优化治疗后的病毒学应答率研究[J]. 中华肝脏病杂志,2015,23(6):412-417.
[8]
张长江, 朱研, 王小红. 慢性丙型肝炎病毒感染的肝外表现[J]. 中华传染病杂志,2011,29(2):124-128.
[9]
Himoto T, Masaki T. Extrahepatic manifestations and autoantibodies in patients with hepatitis C virus infection[J]. Clin Dev Immunol,2012,2012:871401.
[10]
Jadali Z, Alavian SM. Autoimmune diseases co-existing with hepatitis C virus infection[J]. Iran J Allergy Asthma Immunol,2010,9(4):191-206.
[11]
Shen Y, Wang XL, Xie JP, et al. Thyroid disturbance in patients with chronic hepatitis C infection: a systematic review and meta-analysis[J]. J Gastrointestin Liver Dis,2016,25(2):227-234.
[12]
Russo MW, Fried MW. Side effects of therapy for chronic hepatitis C[J]. Gastroenterology,2003,124(6):1711-1719.
[13]
Roti E, Minelli R, Giuberti T, et al. Multiple changes in thyroid function in patients with chronic active HCV hepatitis treated with recombinant interferon-alpha[J]. Am J Med,1996,101(5):482-487.
[14]
Yan Z, Fan K, Fan Y, et al. Thyroid dysfunction in chinese patients with chronic hepatitis C treated with interferon alpha: incidence, long-term outcome and predictive factors[J]. Hepat Mon,2012,12(9):e6390.
[15]
Hwang Y, Kim W, Kwon SY, et al. Incidence of and risk factors for thyroid dysfunction during peginterferon alpha and ribavirin treatment in patients with chronic hepatitis C[J]. Korean J Intern Med,2015,30(6):792-800.
[16]
Huang JF, Huang CK, Yu ML, et al. Thyroid autoantibodies and dysfunction do not impact the treatment efficacy of peginterferon and ribavirin combination therapy in chronic hepatitis C[J]. Hepatol Int,2012,6(3):613-619.
[17]
王晗, 谢娜, 徐军, 等. 慢性丙型肝炎患者干扰素-α治疗后诱发甲状腺功能异常观察[J]. 解放军医学院学报,2015.36(11):1089-1092.
[18]
戴晨琳, 戴晨阳. 慢性丙肝和干扰素治疗与甲状腺疾病的关系[J]. 中华内分泌代谢杂志,2013,29(7):631-633.
[19]
许英霞, 黄雁翔, 郭丹丹, 等. 慢性丙型肝炎合并甲状腺功能异常患者转归情况及抗病毒疗效分析[J]. 北京医学,2014,36(12):1029-1031.
[20]
Tran HA, Jones TL, Gibson R, et al. Thyroid disease is a favorable prognostic factor in achieving sustained virologic response in chronic hepatitis C undergoing combination therapy: A nested case control study[J]. BMC Endocr Disord,2011,11:10.
[21]
Carella C, Mazziotti G, Morisco F, et al. The addition of ribavirin to interferon-alpha therapy in patients with hepatitis C virus-related chronic hepatitis does not modify the thyroid autoantibody pattern but increases the risk of developing hypothyroidism[J]. Eur J Endocrinol,2002,146(6):743-749.
[22]
Huang MJ, Tsai SL, Huang BY, et al. Prevalence and significance of thyroid autoantibodies in patients with chronic hepatitis C virus infection: a prospective controlled study[J]. Clin Endocrinol (Oxf),1999,50(4):503-509.
[23]
Huang JF, Chuang WL, Dai CY, et al. The role of thyroid autoantibodies in the development of thyroid dysfunction in Taiwanese chronic hepatitis C patients with interferon-alpha and ribavirin combination therapy[J]. J Viral Hepat,2006,13(6):396-401.
[24]
Bartolome J, Rodriguez-Inigo E, Quadros P, et al. Detection of hepatitis C virus in thyroid tissue from patients with chronic HCV infection[J]. J Med Virol,2008,80(9):1588-1594.
[25]
桂红莲, 吴彦文, 周惠娟, 等. 干扰素治疗慢性病毒性肝炎发生甲状腺功能异常的临床特征和危险因素[J]. 中华传染病杂志,2013,31(2):87-92.
[26]
Jamil KM, Leedman PJ, Kontorinis N, et al. Interferon-induced thyroid dysfunction in chronic hepatitis C[J]. J Gastroenterol Hepatol,2009,24(6):1017-1023.
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