Li Jing, Fan Peiyao, Xu Zhiqiang, Dong Yi, Wang Fuchuan, Hong Weiguo, Zhao Jinfang, Gao Yinjie, Yan Jianguo, Cao Lili, Zhang Chao, Zhu Shishu, Wang Fu-Sheng, Zhang Min
Peking University 302 Clinical Medical School, Beijing, China.
Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China.
J Clin Transl Hepatol. 2023 Oct 28;11(5):1011-1022. doi: 10.14218/JCTH.2023.00014. Epub 2023 Apr 10.
There is a lack of data supporting the notion that antiviral treatments can benefit children with chronic hepatitis B (CHB) having high viremia and normal or mildly elevated serum alanine aminotransferase (ALT) levels. We aimed to analyze the efficacy of antiviral treatments in children with CHB and explore the factors associated with functional cure.
Forty-eight children with CHB having high viremia and normal or mildly elevated serum ALT levels were screened in this real-world study. Thirty-two children received either interferon-alpha (IFN-α) monotherapy, IFN-α therapy with a nucleoside analog (NA) add-on, or IFN-α and NA combination therapy. The 16 children in the control group did not receive antiviral treatment. All 48 children were available for follow-up assessments for the entire 36-month study period. We identified a functional cure with respect to hepatitis B virus (HBV) DNA loss, loss /seroconversion of circulating hepatitis B e antigen (HBeAg), and loss of hepatitis B surface antigen (HBsAg) with or without seroconversion. Cox regression analysis was employed to evaluate the factors that may have influenced the functional cure.
After 36 months, the cumulative functional cure rate was 56.25% (18/32) in the treated group and 0% (0/16) in the control group (<0.001). In the treated group, the serum HBV DNA levels declined rapidly at the end of a 6-month visit and the cured children achieved a loss rate of 100% (18/18) within 16 months of beginning treatment, compared with 64.29% (9/14) of the uncured children (<0.001). The rates of HBeAg seroconversion were significantly higher among the cured children than among the uncured children (<0.001). All 16 children in the control group maintained high levels of serum HBV DNA and were positive for both serum HBeAg and HBsAg during the entire 36 months of the study period. Functional cure was associated with younger ages (1-6 vs. 7-14 years, =0.013), CD8 T lymphocyte counts (=0.013), and B lymphocyte counts (=0.003). No serious adverse events were observed.
Antiviral treatment achieved a functional cure of CHB in a high proportion of children having high-level viremia and normal or mildly elevated ALT levels. Younger age and high peripheral lymphocyte counts were associated with this functional cure.
缺乏数据支持抗病毒治疗能使慢性乙型肝炎（CHB）且病毒血症高、血清丙氨酸氨基转移酶（ALT）水平正常或轻度升高的儿童获益这一观点。我们旨在分析抗病毒治疗对CHB儿童的疗效，并探索与功能性治愈相关的因素。
在这项真实世界研究中筛选出48例CHB且病毒血症高、血清ALT水平正常或轻度升高的儿童。32例儿童接受了α干扰素（IFN-α）单药治疗、IFN-α联合核苷类似物（NA）附加治疗或IFN-α与NA联合治疗。对照组的16例儿童未接受抗病毒治疗。在整个36个月的研究期间，所有48例儿童均接受了随访评估。我们确定了关于乙肝病毒（HBV）DNA丢失、循环乙肝e抗原（HBeAg）丢失/血清学转换以及乙肝表面抗原（HBsAg）丢失且有无血清学转换的功能性治愈情况。采用Cox回归分析来评估可能影响功能性治愈的因素。
36个月后，治疗组的累积功能性治愈率为56.25%（18/32），对照组为0%（0/16）（<0.001）。在治疗组中，血清HBV DNA水平在6个月随访结束时迅速下降，治愈的儿童在开始治疗后的16个月内实现了100%（18/18）的丢失率，而未治愈的儿童为64.29%（9/14）（<0.001）。治愈儿童的HBeAg血清学转换率显著高于未治愈儿童（<0.001）。在研究的整个36个月期间，对照组的所有16例儿童血清HBV DNA水平维持在高水平，血清HBeAg和HBsAg均为阳性。功能性治愈与年龄较小（1 - 6岁 vs. 7 - 14岁，=0.013）、CD8 T淋巴细胞计数（=0.013）和B淋巴细胞计数（=0.003）相关。未观察到严重不良事件。
抗病毒治疗在很大比例的病毒血症水平高、ALT水平正常或轻度升高的CHB儿童中实现了功能性治愈。年龄较小和外周淋巴细胞计数高与这种功能性治愈相关。
