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台湾地区儿童和青年慢性乙型肝炎患者的干扰素-α治疗:一项长期随访研究

Interferon-alpha treatment in children and young adults with chronic hepatitis B: a long-term follow-up study in Taiwan.

作者信息

Hsu Hong-Yuan, Tsai Hsiu-Yuan, Wu Tzee-Chung, Chiang Cheng-Lun, Ni Yen-Hsuan, Chen Pei-Jer, Chang Mei-Hwei

机构信息

Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.

出版信息

Liver Int. 2008 Nov;28(9):1288-97. doi: 10.1111/j.1478-3231.2008.01746.x. Epub 2008 Apr 7.

Abstract

BACKGROUND/AIMS: The short- and long-term benefits of interferon (IFN)-alpha therapy in young patients with chronic hepatitis B (CHB) acquiring infection perinatally or during early childhood have been questioned.

METHODS

Twenty-one Taiwanese hepatitis B envelope antigen (HBeAg)-positive CHB patients aged 1.8-21.8 years (median 14.0 years) with alanine aminotransferase (ALT)>80 IU/L at entry were enrolled for IFN-alpha therapy. They received IFN-alpha therapy with a dose of 3 MU/m(2)/day three times a week for 24 weeks. A control group included untreated 21 CHB patients closely matched for gender, age, duration of ALT >80 IU/L and HBeAg status. All 42 patients were prospectively followed for 6.5-12.5 years after the end of therapy.

RESULTS

The cumulative rate of virological response [anti-HBe seroconversion and serum hepatitis B virus (HBV)-DNA <10(5) copies/ml] was not different between the IFN-treated patients and control patients at 1 year (41 vs 44%) and at 6 years (88 vs 89%) after stopping treatment. Serum hepatitis B surface antigen loss occurred in two (9.5%) treated patients and in one (4.8%) control patient. Patients with a successful treatment response (anti-HBe seroconversion, HBV-DNA <10(2) copies/ml and ALT normalization at 1 year after stopping treatment) were younger than those without a successful response (P=0.03). A lower pretreatment serum HBV-DNA level (<2 x 10(8) copies/ml) is not only a significant factor to predict successful treatment response (P=0.008) but also has a beneficial effect on the long-term cumulative rate of virological response in IFN-treated patients (P=0.021), but not in control patients. Genotype difference or emergence of a precore stop codon mutant before treatment was not predictive for HBeAg clearance.

CONCLUSION

For young CHB patients in Taiwan with infection occurring perinatally or in early childhood, the real advantage of IFN-alpha therapy was not observed. IFN-alpha therapy showed a beneficial effect on short- and long-term virological outcomes only in those with a lower pretreatment serum HBV-DNA level.

摘要

背景/目的:干扰素(IFN)-α治疗对围生期或幼儿期感染慢性乙型肝炎(CHB)的年轻患者的短期和长期益处受到质疑。

方法

纳入21例台湾地区1.8 - 21.8岁(中位年龄14.0岁)、基线丙氨酸氨基转移酶(ALT)>80 IU/L的乙型肝炎e抗原(HBeAg)阳性CHB患者接受IFN-α治疗。他们接受IFN-α治疗,剂量为3 MU/m²/天,每周3次,共24周。对照组包括21例未经治疗的CHB患者,在性别、年龄、ALT>80 IU/L持续时间和HBeAg状态方面与治疗组密切匹配。所有42例患者在治疗结束后进行了6.5 - 12.5年的前瞻性随访。

结果

在停止治疗后1年(41%对44%)和6年(88%对89%),IFN治疗组和对照组的病毒学应答累积率(抗-HBe血清学转换和血清乙型肝炎病毒(HBV)-DNA<10⁵拷贝/ml)无差异。2例(9.5%)治疗患者和1例(4.8%)对照患者出现血清乙型肝炎表面抗原丢失。治疗反应成功(停止治疗1年后抗-HBe血清学转换、HBV-DNA<10²拷贝/ml且ALT正常化)的患者比未成功的患者年轻(P = 0.03)。较低的基线血清HBV-DNA水平(<2×10⁸拷贝/ml)不仅是预测治疗反应成功的重要因素(P = 0.008),而且对IFN治疗患者的病毒学应答长期累积率有有益影响(P = 0.021),但对对照患者无此影响。治疗前基因型差异或前核心终止密码子突变的出现对HBeAg清除无预测价值。

结论

对于台湾地区围生期或幼儿期感染的年轻CHB患者,未观察到IFN-α治疗的真正优势。IFN-α治疗仅对基线血清HBV-DNA水平较低的患者的短期和长期病毒学结局有有益影响。

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