Autoantibodies and autoimmune disease during treatment of children with chronic hepatitis C.
Autoantibodies and autoimmune disease during treatment of children with chronic hepatitis C.
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DOI：
10.1097/mpg.0b013e3182774cae
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发表时间：
2013-03
影响因子：
2.9
通讯作者：
PEDS-C Clinical Research Network
中科院分区：
文献类型：
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作者：
Molleston JP;Mellman W;Narkewicz MR;Balistreri WF;Gonzalez-Peralta RP;Jonas MM;Lobritto SJ;Mohan P;Murray KF;Njoku D;Rosenthal P;Barton BA;Talor MV;Cheng I;Schwarz KB;Haber BA;PEDS-C Clinical Research Network
在一个具有良好特征的慢性丙型肝炎（CHC）儿童队列中研究了PEG-IFN和利巴韦林治疗期间的自身抗体，以评估自身免疫性疾病的治疗和发展的关系。114名儿童（5-17岁），以前筛选的存在高滴度自身抗体，被随机分配到聚乙二醇干扰素与或不利巴韦林。试验结束后，使用冷冻血清测定抗核抗体（ANA）、抗肝肾微粒体抗体（LKM）、抗甲状腺球蛋白抗体（TG）、抗甲状腺过氧化物酶抗体（TPO）、胰岛素抗体（IA 2）、抗谷氨酸脱羧酶抗体（GAD）。基线时，19%的患者有自身抗体：ANA（8%）、LKM（4%）和GAD（4%）。在第24周和第72周（治疗完成后24周），23%和26%的患者存在自身抗体（与基线相比，p=0.50，0.48）。在治疗期间，一名儿童患上了糖尿病，两名儿童患上了甲状腺功能减退症;没有一名儿童患上了自身免疫性肝炎。在24周时，流感样症状、胃肠道症状和头痛的发生率在有自身抗体的患者中分别为42%、8%和19%，而在无自身抗体的患者中分别为52%、17%和26%（p=0.18、0.36和0.20）。在24周时HCV PCR阴性的儿童中，有自身抗体的儿童的早期病毒学应答/持续病毒学应答率分别为76%/69%，而无自身抗体的儿童为58%/65%（p=0.48）。尽管筛查，我们发现自身抗体通常在基线，治疗期间和之后的CHC。抗体的存在与病毒反应、副作用或自身免疫性肝炎无关。筛查或存档样本的甲状腺和糖尿病相关抗体检测均未发现3例发生明显自身免疫性疾病、糖尿病（1例）和甲状腺功能减退症（2例）的受试者。
Auto-antibodies were studied in a well-characterized cohort of children with chronic hepatitis C (CHC) during treatment with PEG-IFN and ribavirin to assess the relationship to treatment and development of autoimmune disease. 114 children (5–17 years), previously screened for the presence of high titer autoantibodies, were randomized to Peg-IFN with or without ribavirin. Anti-nuclear (ANA), anti-liver-kidney-microsomal (LKM), anti-thyroglobulin (TG), anti-thyroid peroxidase (TPO), insulin (IA2), anti-glutamic acid decarboxylase (GAD) antibodies were measured after trial completion using frozen sera. At baseline,19% had auto-antibodies: ANA (8%), LKM (4%), and GAD (4%). At 24 and 72 weeks (24 weeks after treatment completion), 23% and 26% had auto-antibodies (p=0.50, 0.48 compared to baseline). One child developed diabetes and two hypothyroidism during treatment; none developed autoimmune hepatitis. At 24 weeks, the incidence of flu-like symptoms, gastrointestinal symptoms, and headaches were 42%, 8% and 19% in those with auto-antibodies vs. 52%, 17%, and 26% in those without (p=0.18, 0.36, and 0.20, respectively). In children with negative HCV PCR at 24 weeks, there was no difference in the rate of early virologic response /sustained virologic response respectively in those with auto-antibodies 76%/69%, vs 58%/65% in those without (p=0.48). Despite screening, we found autoantibodies commonly at baseline, during treatment for CHC and after. The presence of antibodies did not correlate with viral response, side effects, or autoimmune hepatitis. Neither screening nor archived samples assayed for thyroid and diabetes-related antibodies identified the 3 subjects who developed overt autoimmune disease, diabetes (1) and hypothyroidism (2).