从儿童到成人的慢性乙型肝炎病毒感染者肝纤维化的临床预测因素。

Clinical Predictors of Liver Fibrosis in Patients With Chronic Hepatitis B Virus Infection From Children to Adults.

机构信息

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

Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan.

出版信息

J Infect Dis. 2018 Apr 11;217(9):1408-1416. doi: 10.1093/infdis/jiy048.

DOI:10.1093/infdis/jiy048

PMID:29390144

Abstract

BACKGROUND

This study aimed to elucidate predictors of liver fibrosis in patients with chronic hepatitis B virus (HBV) infection.

METHODS

Transient elastography was performed to define liver stiffness in 533 patients with chronic HBV infection (mean age ± standard deviation, 30.72 ± 0.57 years). Protein array was performed on serum samples and lysates of Huh7 cells transfected with HBV mutants; the results were confirmed by enzyme-linked immunosorbent assay. Single-nucleotide polymorphisms in the gene encoding interleukin 1β (IL-1β) were examined in patients with chronic HBV infection with and without liver fibrosis.

RESULTS

Male sex, age ≥18 years, and serum α-fetoprotein level >3.6 ng/mL were independent predictors of a liver stiffness measurement of ≥7 kPa (P = .005, .019, and <.001, respectively). HBV e antigen (HBeAg)-negative hepatitis is associated with increased liver stiffness (P < .001). Elevation of the serum IL-1β level was demonstrated in subjects with liver fibrosis. IL-1β was upregulated in Huh7 cells transfected with HBV mutants associated with HBeAg-negative hepatitis. The AA genotype at rs16944 and the CC genotype at rs1143627 in the gene encoding IL-1β were associated with higher serum IL-1β levels and liver fibrosis.

CONCLUSIONS

Male sex, age ≥18 years, elevated α-fetoprotein level, and HBeAg-negative hepatitis are risk factors for liver fibrosis. IL-1β is involved in the progression of liver fibrosis in subjects with HBeAg-negative hepatitis.

摘要

背景

本研究旨在阐明慢性乙型肝炎病毒（HBV）感染患者肝纤维化的预测因素。

方法

对 533 例慢性 HBV 感染患者（平均年龄±标准差，30.72±0.57 岁）进行瞬时弹性成像以确定肝硬度。对血清样本和转染 HBV 突变体的 Huh7 细胞的裂解物进行蛋白质阵列分析；通过酶联免疫吸附试验进行验证。在慢性 HBV 感染患者中检测白细胞介素 1β（IL-1β）基因编码的单核苷酸多态性，这些患者有无肝纤维化。

结果

男性、年龄≥18 岁和血清甲胎蛋白水平>3.6ng/mL 是肝硬度测量值≥7kPa 的独立预测因素（P=0.005、0.019 和<0.001）。HBeAg 阴性肝炎与肝硬度增加相关（P<0.001）。纤维化患者的血清 IL-1β 水平升高。与 HBeAg 阴性肝炎相关的 HBV 突变体转染 Huh7 细胞中，IL-1β 上调。IL-1β 基因编码 rs16944 的 AA 基因型和 rs1143627 的 CC 基因型与较高的血清 IL-1β水平和肝纤维化相关。