抗丙型肝炎病毒治疗过程中甲状腺功能异常与病毒学应答关系研究

Prevalence of thyroid dysfunction and its impact on virologic response in patients with hepatitis C receiving pegylated interferon-α and ribavirin

目的：探讨聚乙二醇干扰素（Peg-IFN）联合利巴韦林（RBV）治疗慢性丙型肝炎患者发生甲状腺功能异常的转归及其对抗病毒疗效的影响。方法204例（HCV基因1b型感染173例，2a型9例，3b型2例，未分型20例）慢性丙型肝炎患者应用Peg-IFN联合RBV抗病毒治疗。对于基因1型和未分型者治疗48 w，对于基因2型和3型治疗24 w。采用化学发光免疫分析法检测血清游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）、超敏促甲状腺激素（sTSH）；采用间接免疫荧光法检测血清抗甲状腺球蛋白抗体（Tg-Ab）、抗甲状腺过氧化物酶抗体（TPOAb）、抗促甲状腺激素受体抗体（TRAb）、抗甲状腺微粒体抗体。结果在治疗过程中，发生甲状腺功能异常43例（19.0%），其中甲状腺功能减退症7例（16.3%），亚临床甲状腺功能减退症17例（39.5%），甲状腺功能亢进症11例（25.6%），亚临床甲状腺功能亢进症8例（18.6%）；甲状腺功能异常集中发生于治疗后24～36 w；在观察结束时，37例甲状腺功能异常患者自发或者经药物治疗后甲状腺功能恢复正常，6例患者仍需要密切监测甲状腺功能或服用抗甲状腺药物；43例甲状腺功能异常与161例无甲状腺功能异常患者RVR、EVR、ETVR、SVR、治疗结束后96 w病毒学应答率差异均无统计学意义（P＞0.05）。结论 Peg-IFN联合RBV治疗慢性丙型肝炎患者诱发甲状腺功能异常的发生率为19.0%，大部分是可逆的，甲状腺功能异常不影响抗病毒疗效。

Objective To explore the prevalence of thyroid dysfunction in patients with chronic hepatitis C during pegylated interferon（Peg-IFN） combined with ribavirin（RVB） therapy and its impact on antiviral efficacy. Methods 204 patients （HCV 1b infection in 173,2a in 9,3b in 2,and undefined in 20） with chronic hepatitis C who had normal thyroid function at the beginning of the study received the treatment of Peg-IFN combined with RBV. The regimen lasted for 48 weeks for patients with HCV 1 and undefined genotypes,and for 24 weeks for patients with genotype 2 and 3. Serum FT3,FT4,sTSH,Tg-Ab,TPOAb and TRAb were detected. Results Thyroid dysfunction occurred in 43 patients （19.0%） during the PEG-IFN/RBV treatment,among whom 16.3% presented with hypothyroidism,39.5% with subclinical hypothyroidism,25.6% with hyperthyroidism,and 18.6% with subclinical hyperthyroidism. Thyroid dysfunction mainly occurred at 24 to 36 week treatment. At the end of observation,37 patients with thyroid dysfunction recovered spontaneously or after medical intervention, however,six patients with high serum titer of thyroid autoantibodies still needed close monitoring of thyroid function and sustained administration of anti-thyroid agents. There were no significant differences as respect to RVR,EVR,ETVR and SVR between 43 patients with thyroid dysfunction and 161 with normal thyroid function （P 〉0.05）. Conclusion Thyroid dysfunction occurs in patients with chronic hepatitis C during Peg -IFN/RBV treatment. The thyroid dysfunctions are reversible,and do not influence the antiviral efficacy.