聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙型肝炎合并慢性淋巴细胞性甲状腺炎的临床观察

Clinical observation of hashimoto thyroiditis in patients with chronic hepatitis C undergoing pegylated-interferon aipha-2a and ribavirin combination therapy

目的观察干扰素d对慢性丙型肝炎合井慢性淋巴细胞性甲状腺炎患者的抗病毒疗效和对甲状腺功能的影响。方法对21例治疗前及治疗中抗甲状腺过氧化物酶抗体（A—TPO）升高，并诊断为慢性淋巴细胞性甲状腺炎的慢性丙型肝炎患者，初始给予普通干扰素a-lb 200万单位，隔日1次，肌肉注射2～3次后改为400万单位，隔日1次，肌肉注射2～3次后皮下注射聚乙二醇干扰素a-2a135～180μg，每周1次，直至疗程结束，所有患者服用利巴韦林为0．9～1．2g／d，分3次口服。观察治疗过程中及治疗结束后24周患者甲状腺功能的变化及抗病毒治疗的效果。应用PEMS3．1统计软件，计量资料采用和检验或口检验，计数资料采用石。检验或Fisher精确概率法。结果在抗病毒治疗中甲状腺功能异常发生率：慢性丙型肝炎合并慢性淋巴细胞性甲状腺炎的患者为71．4％（15／21），未合并慢性淋巴细胞性甲状腺炎的慢性丙型肝炎患者为30．2％（26／86），二组比较，x^2=12．1995，P〈0．01，差异有统计学意义。慢性丙型肝炎合并慢性淋巴细胞性甲状腺炎患者治疗结束24周，仍有90．5％（19／21）的患者A-TPO高于正常值上限2倍以上，73．3％（11／15）的患者甲状腺功能异常。甲状腺功能异常者以甲状腺功能减退表现为主，并且均对左甲状腺素钠敏感。两组患者抗病毒治疗4、12周，治疗结束后24周病毒学应答率比较，差异无统计学意义。结论干扰素a治疗幔性丙型肝炎合并慢性淋巴细胞性甲状腺炎患者，其甲状腺功能异常的发生率明显增高，在严密监测下可完成抗病毒疗程，可与慢性丙型肝炎患者获同样的抗病毒疗效。

Objeclive To investigate the relation of thyroid function with hashimoto thyroiditis （HT,an autoimmune disease of unknown etiology also known as chronic lymphocytic thyroiditis） in patients with chronic hepatitis C （CHC） receiving treatment with pegylated-interferon-alpha （Peg-IFN^t） based on the observation that HT is common among individuals undergoing IFN-based therapy. Methods One-hundred- and-seven patients with chronic hepatitis C were enrolled for study between January 2008 and December 2010. Thyroid function was assessed by electrochemiluminescence assays to detect serum levels of anti- thyroid peroxidase （A-TPO） antibodies, thyroid stimulating hormore （TSH）, and free thyroxine （FT4） prior to initiation of the IFN-based therapy. The treatment strategies （drugs, doses, schedules） were designed according to HT status （CHC with HT, or CHC without HT）. Patients were monitored during the 24 weeks of treatment （including measuring serum alanine aminotransferae （ALT）, TSH, and FT4 every two to four weeks, and HCV RNA every four weeks） so that the IFNct dose could be adjusted and thryoid medications （levothyroxine sodium or methimazole） added as necessary. The response rate at end of treatment （week 24） was assessed. Results Twenty-one of the CHC patients were diagnosed with HT, and the incidence of thyroid dysfunction among the CHC patients with HT was 71.4% （15/21）; among the CHC patients with no HT, the incidence of thyroid dysfunction was significantly lower （30.2% （26/86）, x^2 = 12.1995, P 〈 0.01）. In the CHC patients with HT, 90.5% （19/21） had serum levels of A-TPO antibodies that were 〉/2-times higher than the normal value at the end of treatment. Of the 15 CHC patients with HT and thyroid dysfunction, 73.3% （11/15） continued to show thyroid dysfunction at the end of treatment. Hypothyroidism was the most common form of thyroid dysfunction observed （4/11）, and all of those patients responded to levothyroxine sodium treatment. The virological response rates of the two groups （CHC with HT and CHC without HT） were not significantly different at any time point examined （treatment week 4, 12, and 24, P 〉 0.05）. Conclusion The incidence of thyroid dysfunction is significantly higher among CHC patients with HT than among CHC patients without HT. If suspected, these patients should be carefully monitored because the clinical symptoms of thyroid dysfunction are not obvious and the drug therapy should be carefully adjusted to minimize the thyroid dysfunction while maximizing the antiviral effect.