Franulović Orjena Zaja, Rajacić Nada, Lesar Tatjana, Kuna Andrea Tesija, Morić Bernardica Valent
University of Zagreb, Sestre milosrdnice- University Hospital Centre, Department of Pediatric Gastroenterology and Hepatology, Zagreb, Croatia.
Coll Antropol. 2012 Sep;36(3):973-9.
The conventional treatment of autoimmune hepatitis (AIH) in children, which includes prednisone alone or in combination with azathioprine, induces remission in most cases but is often associated with poorly tolerated side effects. To avoid the adverse effects, Alvarez et al. introduced an alternative treatment regimen, using cyclosporine A (CyA) as primary immunosuppression. We carried out a retrospective study to evaluate the efficacy and tolerance of CyA treatment in children and adolescents with AIH treated in our center. During 2000-2010 period, nine children (6 female) aged 5-17.5 years, were diagnosed with AIH according to established international criteria. Following the suggested protocol, CyA was administered orally and when the transaminases tended to normalise, dose was adjusted to lover serum levels. Conversion to low dose of prednisone and azathioprine was started after 6 months, with gradual tapering and discontinuation of CyA. All nine patient had elevated transaminases and gammaglobulin levels, with proven histological changes typical for AIH in 8 patients that underwent liver biopsy (in one patient biopsy was contraindicated due to the prolonged prothrombin time). Serum ANA/SMA autoantibodies were positive in all but one patient, who had positive anti-LKM1. Complete or near complete and persistent normalisation of transaminase activity was observed in 8/9 patients within first 6 to 12 months. In one patient with partial response, an overlap syndrome was established. After ursodeoxycholic acid was added complete remission was observed. All patients had excellent clinical course and histological improvement. During the long-term follow-up (1.5-9 yrs; median 4.5 yrs), biochemical relapse occured in one patient after discontinuation of maintenance corticosteroid dose. Despite registered improvement, none of the patients fulfilled the criteria for therapy discontinuation, so all of them are still receiving maintenance doses of prednisone or azathioprine. The applied protocol allowed for the control of the liver inflammatory disease in all of our patients and protected them from the side effects related to steroid treatment. Side effects of CyA were minimal and were well tolerated.
儿童自身免疫性肝炎(AIH)的传统治疗方法,包括单独使用泼尼松或与硫唑嘌呤联合使用,在大多数情况下可诱导病情缓解,但往往伴有耐受性差的副作用。为避免这些不良反应,阿尔瓦雷斯等人引入了一种替代治疗方案,使用环孢素A(CyA)作为主要免疫抑制剂。我们进行了一项回顾性研究,以评估CyA治疗在我们中心接受治疗的儿童和青少年AIH患者中的疗效和耐受性。在2000年至2010年期间,9名年龄在5至17.5岁的儿童(6名女性)根据既定的国际标准被诊断为AIH。按照建议方案,口服CyA,当转氨酶趋于正常时,调整剂量以降低血清水平。6个月后开始转换为低剂量的泼尼松和硫唑嘌呤,并逐渐减少CyA剂量直至停药。所有9名患者的转氨酶和γ球蛋白水平均升高,8名接受肝活检的患者证实有AIH典型的组织学改变(1名患者因凝血酶原时间延长而禁忌活检)。除1名抗LKM1阳性的患者外,所有患者的血清ANA/SMA自身抗体均为阳性。8/9的患者在最初的6至12个月内转氨酶活性完全或接近完全且持续正常化。1名部分缓解的患者被诊断为重叠综合征。添加熊去氧胆酸后观察到完全缓解。所有患者的临床病程和组织学均有改善。在长期随访(1.5至9年;中位时间4.5年)期间,1名患者在停用维持性皮质类固醇剂量后出现生化复发。尽管有改善记录,但没有患者达到停药标准,因此他们仍在接受泼尼松或硫唑嘌呤的维持剂量。所应用的方案使我们所有患者的肝脏炎症性疾病得到控制,并使他们免受与类固醇治疗相关的副作用。CyA的副作用最小,耐受性良好。
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