Department of Infectious Diseases, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai 201102, China; Key Development of Program of Children's Hospital of Fudan University, National Children's Medical Center, Shanghai 201102, China.
Department of Infectious Diseases, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai 201102, China; Key Development of Program of Children's Hospital of Fudan University, National Children's Medical Center, Shanghai 201102, China.
Int J Infect Dis. 2022 Oct;123:112-118. doi: 10.1016/j.ijid.2022.08.017. Epub 2022 Aug 23.
Chronic hepatitis B (CHB) is associated with high morbidity and mortality. We aimed to investigate associations between hepatic histology and clinical characteristics in treatment-naïve children with CHB in Shanghai, China.
The liver biopsy specimens of 278 treatment-naïve children with CHB virus infection were scored for inflammation and fibrosis, and correlations with clinical and laboratory data were determined.
CHB clinical, virologic, and pathologic features were studied in 278 treatment-naïve children (177 [63.7%] males) in Shanghai, China. Maternal sera were positive for hepatitis B surface antigen for 277 children. At biopsy, 87.4% of patients were hepatitis B e antigen-positive. The median age at biopsy was 5.1 years (interquartile range 2.8-8.4 years). Hepatitis B virus (HBV) deoxyribonucleic acid levels were generally high (mean 7.4 log IU/ml), as were levels of serum alanine aminotransferase (ALT, median 105 U/l). Using the Metavir histology activity index scoring system, no, mild, moderate, and severe inflammation were seen in 2.9%, 22.3%, 73.4%, and 1.4% of patients, respectively. No fibrosis, mild fibrosis, moderate fibrosis, and cirrhosis were seen in 11.5%, 32.7%, 47.5%, and 8.3% of patients, respectively. When the serum ALT level was ≤80 (two times the upper limit of normal) and >80 U/l, the inflammation score (P <0.0001) was significantly different, and the fibrosis score was also significantly different (P <0.0001). Inflammation and fibrosis were aggravated with increasing ALT levels. Fibrosis scores were significantly higher in children aged ≤3 than aged >3 years (P <0.0001). The rates of moderate fibrosis and cirrhosis were higher in children aged ≤3 years at biopsy. No correlations were found between histologic changes and sex, HBV genotype, or HBV deoxyribonucleic acid level.
Substantial heterogeneity in inflammatory and fibrotic levels was observed in treatment-naïve children with CHB in Shanghai, China. Serum ALT levels >80 U/l may be a strong indicator of the degree of hepatic inflammation and fibrosis severity. Moderate fibrosis and cirrhosis can appear in children aged 3 years or younger.
慢性乙型肝炎（CHB）与高发病率和高死亡率相关。本研究旨在探索中国上海未经治疗的 CHB 患儿的肝脏组织学与临床特征之间的关系。
对 278 例未经治疗的乙型肝炎病毒感染患儿的肝活检标本进行炎症和纤维化评分，并确定与临床和实验室数据的相关性。
在中国上海，对 278 例未经治疗的 CHB 患儿（177 例[63.7%]为男性）的 CHB 临床、病毒学和病理特征进行了研究。277 例患儿的母亲血清乙型肝炎表面抗原阳性。肝活检时，87.4%的患儿乙型肝炎 e 抗原阳性。肝活检时的中位年龄为 5.1 岁（四分位间距 2.8-8.4 岁）。乙型肝炎病毒（HBV）脱氧核糖核酸水平普遍较高（平均 7.4 log IU/ml），血清丙氨酸氨基转移酶（ALT）水平也较高（中位数 105 U/l）。采用 Metavir 组织学活动指数评分系统，分别有 2.9%、22.3%、73.4%和 1.4%的患儿无炎症、轻度炎症、中度炎症和重度炎症。无纤维化、轻度纤维化、中度纤维化和肝硬化的患儿分别占 11.5%、32.7%、47.5%和 8.3%。当血清 ALT 水平≤80（正常值上限的两倍）和>80 U/l 时，炎症评分（P<0.0001）差异显著，纤维化评分也显著不同（P<0.0001）。随着 ALT 水平的升高，炎症和纤维化加重。肝活检时年龄≤3 岁的患儿纤维化评分显著高于年龄>3 岁的患儿（P<0.0001）。肝活检时年龄≤3 岁的患儿中度纤维化和肝硬化的发生率较高。组织学变化与性别、HBV 基因型或 HBV 脱氧核糖核酸水平无相关性。
在中国上海未经治疗的 CHB 患儿中，炎症和纤维化水平存在明显异质性。血清 ALT 水平>80 U/l 可能是反映肝炎症和纤维化严重程度的一个强有力指标。3 岁或以下的儿童可能出现中度纤维化和肝硬化。
