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儿童慢性丙型肝炎干扰素α治疗效果的研究。

Studies of the effectiveness of interferon alpha treatment for chronic hepatitis C in children.

作者信息

Czerwionka-Szaflarska M, Chrobot A, Szaflarska-Szczepanik A

机构信息

Chair and Department of Pediatrics, Allergology and Gastroenterology, Medical University, ul. Ujejskiego 75, 85-168 Bydgoszcz, Poland.

出版信息

Med Sci Monit. 2000 Sep-Oct;6(5):964-70.

Abstract

INTRODUCTION

The significance of hepatitis C infection in Poland, particularly in a pathology of the developmental age still increased. The aim of the study was the analysis of interferon alpha therapy efficacy in children with chronic C hepatitis.

MATERIAL AND METHODS

30 children (aged from 3 years to 15 years, 16 females, 14 males) were included in the study. In each patient HCV infection was confirmed by the serological, molecular (with identification of HCV genotype) and histopathological methods. The duration of observation of HCV-infected children after the diagnosis was made followed for at least 6 months. Transaminase level in each case was 50% higher than normal. The schema of interferon alpha treatment was: 3 MU 3 times a week subcutaneously for 25 weeks. Time of observation started at the beginning of the therapy and finished 1 year after the end of the treatment.

RESULTS

The analysis of the HCV genotypes showed the predominance of the genotype 1 (66.7%): subtype 1a was found in 20% patients, subtype 1b--in 43.5% children. Genotype 4 (subtype 4c4d or 4b) was confirmed in 30% patients, genotype 3 (subtype 3a) in 3.3% patients. In the histopathological picture of the liver predominated minimal or moderate inflammation activity (grading: 1--in 50%, 2--in 46.6%, 3--in 3.4%) and little fibrosis (staging: 0--in 80%, 1--in 13.3%, 2--in 6.7%). In many children mild side effects of interferon alpha therapy were observed: pseudoinfluenzal symptoms (in 46.7%), lack of appetite (in 16.7%), abdominal pain (in 10%), thrombocytopenia (in 6.7%), granulocytopenia, hair loss, irritability, itching of the skin (in 3.4%). At the end of therapy in 36.7% patients serum HCV-RNA was undetectable. The percentage of children without serum HCV-RNA decreased 6 months after the end of therapy to 20% patients and a year after the end of therapy to only 13.6% children. In children with HCV-RNA elimination was observed early reduction of ALT level. For the definition of the predictive factors of good prognosis patients were divided into 2 groups: group I (without HCV-RNA elimination at the end of the treatment) and group II (patients HCV-RNA negative a year after the end of therapy). Both group of children were similar in respect of age, disease duration and interferon alpha dosis/m2. At the beginning of the treatment mean ALT level was statistically higher in group II than in group I. IL-2 level was significant higher in group II than at the beginning, after 2 and 4 months of the therapy. There were no significant differences in IL-1 beta, IL-4 and IL-6 level between patients in group I and II. The differences in ALT activity during IFN-therapy between 2 groups of patients were statistically significant; since second month of therapy higher ALT level was observed in a group of patients without HCV-RNA elimination. In the histopathological picture of the liver a year of the end of therapy in 20% children reduction of inflammatory activity and progression of fibrosis in both group of patients was observed.

CONCLUSIONS

Because of a little efficacy, high costs, psychological load of young patients and possible following consequences of the interferon alpha therapy it is necessary to manage the further researches to find a new method of treatment of chronic C hepatitis. High ALT activity and elevated IL-2 level before treatment seems to be predictive factors of the good response to interferon alpha therapy.

摘要

引言

丙型肝炎感染在波兰的重要性,尤其是在发育年龄阶段的病理学方面,其重要性仍在增加。本研究的目的是分析干扰素α治疗慢性丙型肝炎儿童的疗效。

材料与方法

30名儿童(年龄从3岁至15岁,16名女性,14名男性)纳入本研究。通过血清学、分子学(鉴定HCV基因型)和组织病理学方法确诊每位患者的HCV感染。确诊HCV感染儿童后的观察期至少为6个月。每例患者的转氨酶水平比正常高50%。干扰素α治疗方案为:每周皮下注射3 MU,共3次,持续25周。观察时间从治疗开始时起,至治疗结束后1年结束。

结果

HCV基因型分析显示基因型1占主导(66.7%):20%的患者为1a亚型,43.5%的儿童为1b亚型。30%的患者确诊为基因型4(4c4d或4b亚型),3.3%的患者为基因型3(3a亚型)。在肝脏组织病理学图像中,以轻度或中度炎症活动为主(分级:1级占50%,2级占46.6%,3级占3.4%),纤维化程度较轻(分期:0期占80%,1期占13.3%,2期占6.7%)。在许多儿童中观察到干扰素α治疗的轻度副作用:假性流感症状(46.7%)、食欲不振(16.7%)、腹痛(10%)、血小板减少(6.7%)、粒细胞减少、脱发、易怒、皮肤瘙痒(3.4%)。治疗结束时,36.7%的患者血清HCV - RNA检测不到。治疗结束6个月后,血清HCV - RNA阴性的儿童比例降至20%,治疗结束1年后仅为13.6%。在HCV - RNA清除的儿童中,观察到ALT水平早期降低。为确定预后良好的预测因素,将患者分为两组:第一组(治疗结束时未清除HCV - RNA)和第二组(治疗结束1年后HCV - RNA阴性的患者)。两组儿童在年龄、病程和干扰素α剂量/m²方面相似。治疗开始时,第二组的平均ALT水平在统计学上高于第一组。治疗2个月和4个月后,第二组的IL - 2水平显著高于治疗开始时。第一组和第二组患者的IL - 1β、IL - 4和IL - 6水平无显著差异。两组患者在干扰素治疗期间的ALT活性差异具有统计学意义;从治疗第二个月起,未清除HCV - RNA的患者组ALT水平较高。治疗结束1年后,在20%的儿童肝脏组织病理学图像中观察到两组患者的炎症活动减轻和纤维化进展。

结论

由于疗效欠佳、成本高昂、年轻患者的心理负担以及干扰素α治疗可能产生的后续后果,有必要进一步开展研究以寻找治疗慢性丙型肝炎的新方法。治疗前ALT活性高和IL - 2水平升高似乎是对干扰素α治疗反应良好的预测因素。

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