慢性丙型肝炎抗病毒治疗患者甲状腺功能异常及其影响因素

Analysis of thyroid dysfunction and influencing factors in chronic hepatitis C patients treated with peg-IFNα- 2a and ribavirin

目的探讨慢性丙型肝炎（CHC）抗病毒治疗患者甲状腺功能异常隋况并分析其影响因素。方法对194例CHC患者应用聚乙二醇干扰素（PegIFN）α-2a联合利巴韦林（RBV）治疗，疗程48周，停药后随访24周。按治疗结束时甲状腺功能分为正常组和异常组。采用病例对照方法，回顾性分析患者治疗前后甲状腺功能异常隋况及其影响因素。计数资料采用z。检验，计量资料采用f检验；对有统计学意义的性别、甲状腺自身抗体进行logistic回归分析。结果治疗结束时甲状腺功能异常52例，占26．80％，正常142例，占73．20％ 其中甲状腺功能亢进症（甲亢）1例，占0．52％，甲状腺功能减退症（甲减）10例，占5．15％）；亚临床甲亢4例，占2．06％），亚临床甲减37例，占19．07％ 抗病毒治疗前后甲状腺功能异常率差异有统计学意义（12．37％对比26．80％，X2=12．829，P〈0．05）。影响甲状腺功能的因素主要有性别（X2=4．038，P〈0．05，95％ CI1．016～3．040）和甲状腺自身抗体P〈0．05，95％凹：1．681～36．183）；但抗病毒疗效差异无统计学意义；细胞因子中，正常和异常组自细胞介素6（IL-6）差异有统计学意义[（27．08±14．90）ng／L对比（11．65±5．46）ng／L，t=3．127，p〈0．05，95％CI：5．28～25．581，治疗24周末：2组IL-6差异无统计学意义[（6．30±2．47）ng／L对比（6．81±2．80）ng／L，f=0．352，P〉0．051。甲状腺功能异常组治疗前后IL-6差异无统计学意义[（11．65±5．46）ng／L对比（6．81±2．80）ng／L，f=1．997，JP〉0．051。甲状腺功能正常组治疗前后IL-6差异有统计学意义[（27．08±14．90）ng／L对比（6．30±2．47）ng／L，f=3．632，p〈O．05）。结论Peg-IFNα-Za联合RBV治疗CHC患者可引起甲状腺功能异常，其中引起甲状腺功能减退症常见。女性，甲状腺自身抗体阳性患者Peg-IFNα2a联合RBV治疗后容易发生甲状腺功能异常。IL-6可作为预测Peg-IFNα2a联合RBV治疗引起甲状腺功能异常的辅助诊断参考指标。

Objective To analyze the frequency of thyroid dysfunction and determine its influencing factors in chronic hepatitis C （CHC） patients treated with pegylated-interferon alpha （peg-IFNα）-2a and fibavirin （RBV） combination therapy. Methods A total of 194 CHC patients were treated with peg-IFNα- 2a and RBV for 48 weeks. Development of thryoid dysfunction was recorded. Clinical and biological factors from pre-treatment （baseline） to post-treatment were statistically analyzed to determine correlation with thyroid dysfunction in this patient population. Results Fifty-two （26.80%） of 194 peg-IFNα-2a/RBV- treated patients developed thyroid dysfunction. Dysfunction severity ranged from hyperthyroidism 07 = 1, 0.52%） and hypothyroidism 07 = 10, 5.15%） to subclinical hyperthyroidism 07 = 4, 2.06%） and subclinical hypothyroidism （n = 37, 19.07%）. The dysfunction rate was significantly higher after peg-IFNct-2a/RBV treatment （26.80% vs. 12.37% at baseline, x2 = 12.829, P 〈 0.05, odds ratio （OR） = 0.386, 95% confidence interval （CI）： 0.226-0.657）, in females （33.00% vs. 20.21% in males, P 〈 0.05, 95% CI： 1.016-3.040）, and in thyroid auto-antibody positive patients （64.29% vs. 23.89% in negative patients, P 〈 0.05, 95% CI： 1.681- 36.183）. Early virological response did not have any significant effect on dysfunction rate （23.00% vs. 30.85% no early virological response, x2 = 1.522, P 〉 0.05） nor did end of treatment response （27.19% vs. 26.25% no response at end of treatment, x2 = 0.021, P 〉 0.05）. Patients who developed thyroid dysfunction had higher interleukin （IL）-6 at baseline （i.e. before peg-IFNα-2a/RBV treatement） （27.08± 14.90 vs. 11.65 ± 5.46 in patients who maintained normal thyroid function, t = 3.127, P 〈 0.05, 95% CI： 5.28-25.58）. IL-6 levels were not significantly different between the two groups at 24 weeks （6.30 ± 2.47 vs. 6.81 ±2.80, t = 0.352,P 〉 0.05）. IL-6 levels before and after 48 weeks of treatment in normal thyroid function patients were 27.08 ±14.90 and 6.30 ±2.47, t = 3.632,P 〈 0.05, and in thyroid dysfunction patients were 11.65 ±5.46 and 6.81 ±2.80, t = 1.997, P 〉 0.05. Conclusion Peg-IFNα-2a/RBV combination therapy may eanse thyroid dysfunction, especially hypothyroidism, in CHC patients. Female sex and thyroid auto-antibody positivity may put CHC patients at higher risk of developing thyroid dysfunction during peg-IFNα-2a/RBV therapy. Elevated IL-6 may be a predictive marker ofpeg-IFNα-2a/RBV-indueed thyroid dysfunction.