儿童慢性乙型肝炎肝组织病理及不同治疗方案的疗效和安全性的回顾性研究

摘要/Abstract

摘要： 目的探讨18岁以下儿童慢性乙型肝炎(CHB)肝组织病理及不同治疗方案的疗效和安全性。方法回顾性分析2011年1月—2020年12月厦门市中医院因肝功能异常收住院的<18周岁的CHB患者,分析其基线特征及肝脏病理结果,核苷(酸)类似物、干扰素类治疗患者的疗效及不良反应;率的比较采用χ²检验。结果 (1)51例完成肝组织活检的患者肝脏炎症分级G≥2占96.1%,S≥2占33.3%,14～18岁的患者炎症分级G3占37.0%、G4占7.4%,纤维化分期S3占18.5%、S4占7.4%;(2)未抗病毒治疗组占27.8%(35/126),<7岁占65.7%;HBeAg阳性CHB患者抗病毒治疗组的72周HBV DNA阴性率、HBeAg血清学转换率、HBsAg血清学转换率分别为62.0%(49/79)、46.8%(37/79)、20.3%(16/79),远高于未抗病毒治疗组(2.9%(1/35)、2.9%(1/35)、0(0/35)),差异有统计学意义;(3)干扰素类治疗组72周HBeAg血清学转换率、HBsAg血清学转换率为:48.5%(33/68)、20.6%(14/68),高于核苷(酸)类似物(NAs)治疗组(27.3%(3/11)、9.1%(1/11)),差异无统计学意义;(4)<7岁组48周与72周HBV DNA阴性率、HBeAg血清学转换率、HBsAg血清学转换率分别为83.3%(15/18)、64.7%(11/18)、27.8%(5/18)与72.2%(13/18)、66.7%(12/18)、61.1%(11/18),均高于7～14岁组[分别为:57.9%(11/19)、36.8%(7/19)、5.3%(1/19)与63.2%(12/19)、36.8%(7/19)、5.3%(1/19)]及14～18岁组[分别为:48.4%(15/31)、38.7%(12/31)、3.2%(1/31)与51.6%(16/31)、45.2%(14/31)、6.5%(2/31)],部分有统计学意义;(5)干扰素α(IFNα)与聚乙二醇干扰素α(Peg-IFNα)抗病毒治疗72周HBV DNA阴性率、HBeAg血清学转换率、HBsAg血清学转换率[分别为50.0%(18/36)、47.2%(17/36)、19.4%(7/36)与71.9%(23/32)、50.0%(16/32)、21.9%(7/32)]差异无统计学意义;(6)HBeAg阴性CHB患者72周HBsAg血清学转换率为0(0/6),低于HBeAg阳性组CHB(20.3%(16/79)),差异无统计学意义;(7)NAs抗病毒治疗未见明显不良反应;儿童干扰素治疗的不良反应与成人相似,IFNα与Peg-IFNα的不良反应无差别,最常见不良反应为流感样症状75.3%(55/73)及骨髓抑制74.0%(54/73)。结论儿童CHB 患者多伴有肝脏炎症活动及不同程度的纤维化,抗病毒治疗干扰素疗效优于核苷(酸)类似物,年龄越小,抗病毒应答率越高;儿童干扰素治疗的不良反应与成人相似,严重不良反应少。

关键词: 儿童, 慢性乙型肝炎, 干扰素, 不良反应

Abstract: Objective To investigate the liver pathological diagnosis of chronic hepatitis B (CHB) in children under 18 years old and the efficacy and safety of different therapies. Methods A retrospective analysis was performed for the baseline characteristics, liver pathological results, efficacy and side effects of nucleoside (acid) analogues (NAs) and interferon in patients with CHB under 18 years old who were hospitalized due to abnormal liver function from January 2011 to December 2020 in Xiamen Hospital of Traditional Chinese Medicine. Chi-square test was used to compare the rates. Results (1) 51 patients who completed liver tissue biopsy had liver inflammation grading G ≥ 2 accounting for 96.1%, S ≥ 2 accounting for 33.3%. Patients aged 14-18 had inflammation grading G3 accounting for 37.0%, G4 accounting for 7.4%, and fibrosis grading S3 accounting for 18.5%,grading S4 accounting for 7.4%, respectively. (2) Patients who refused antiviral treatment were accounted for 27.8% (35/126), and 65.7% of them were under 7 years old. The HBV DNA negative rate, HBeAg seroconversion rate and HBsAg seroconversion rate of HBeAg positive CHB patients in the antiviral treatment group at Week 72 were 62.0% (49/79), 46.8% (37/79) and 20.3% (16/79), which were much higher than those in the non-antiviral treatment group (2.9% (1/35), 2.9% (1/35) and 0 (0/35)), and the difference was statistically significant. (3) The HBeAg seroconversion rate and HBsAg seroconversion rate in interferon treatment group at Week 72 were 48.5% (33/68) and 20.6% (14/68), which were higher than those in NAs treatment group (27.3% (3/11) and 9.1% (1/11)), and the difference was not statistically significant. (4) The HBV DNA negative rate, HBeAg seroconversion rate, and HBsAg seroconversion rate in the<7 years old group at 48 and 72 weeks were 83.3% (15/18), 64.7% (11/18), 27.8% (5/18), and 72.2% (13/18), 66.7% (12/18), 61.1% (11/18), respectively. Both were higher than those in the 7-14 years old group (57.9% (11/19), 36.8% (7/19), 5.3% (1/19) and 63.2% (12/19), 36.8% (7/19), 5.3% (1/19),respectively) and the 14-18 years old group (48.4% (15/31), 38.7% (12/31), 3.2% (1/31) and 51.6% (16/31), 45.2% (14/31), 6.5% (2/31), respectively), some of which had the statistically significant differences. (5) The HBV DNA negative rate, HBeAg seroconversion rate, and HBsAg seroconversion rate after 72 weeks of antiviral treatment with Interferon α (IFN α) or Pegylated interferon α (Peg-IFN α) were 50.0% (18/36), 47.2% (17/36), 19.4% (7/36) or 71.9% (23/32), 50.0% (16/32), 21.9% (7/32), respectively, with no statistically significant difference. (6) The HBsAg seroconversion rate of HBeAg negative CHB patients at Week 72 was 0 (0/6), which was lower than that of HBeAg positive CHB (20.3% (16/79)), and the difference was not statistically significant. (7) NAs showed no obvious adverse reaction after antiviral treatment; The adverse reactions of interferon treatment in children were similar to those in adults. The adverse reactions of IFN α and Peg-IFN α were not statistically different. The most common adverse reactions were influenza-likely symptoms in 75.3% (55/73) and myelosuppression in 74.0% (54/73). Conclusion Children with CHB are frequently accompanied by liver inflammatory activity and varying degrees of fibrosis. The antiviral treatment effect of interferon in children with CHB is better than that of nucleoside (acid) analogues. The younger guys, the better antiviral response. The adverse reactions of interferon therapy in children were similar to those in adults, with fewer severe adverse reactions.

Key words: Child, Chronic Hepatitis B, Interferons, Adverse reactions

林彬彬, 汤钰菁, 欧阳丽娟, 阮清发. 儿童慢性乙型肝炎肝组织病理及不同治疗方案的疗效和安全性的回顾性研究[J]. 肝脏, 2024, 29(11): 1386-1391.

LIN Bin-bin, TANG Yu-jing, OUYANG Li-juan, RUAN Qing-fa. A retrospective study on liver pathological diagnosis and efficacy and safety of different therapies in children with chronic hepatitis B[J]. Chinese Hepatolgy, 2024, 29(11): 1386-1391.

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