血清 M2BPGi 水平在诊断慢性乙型肝炎病毒感染治疗患者中显著肝纤维化和肝硬化中的作用。

Role of serum M2BPGi levels on diagnosing significant liver fibrosis and cirrhosis in treated patients with chronic hepatitis B virus infection.

机构信息

Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.

State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China.

出版信息

Clin Transl Gastroenterol. 2018 Jun 19;9(6):163. doi: 10.1038/s41424-018-0020-9.

BACKGROUND

Mac-2-binding protein glycosylation isomer (M2BPGi), a novel serum marker for liver fibrosis, was seldom studied in chronic hepatitis B (CHB). We aimed to evaluate its role on diagnosing significant fibrosis and cirrhosis in treated CHB patients.

METHODS

CHB patients treated with nucleos(t)ide analogues (NAs) with baseline liver biopsies and retrievable serum samples were recruited. Paired liver biopsies were performed in patient subgroups at 1 and 3 years.

RESULTS

In total, 327 NA-treated CHB patients (M:F = 229:98; median age 38.1 years) were recruited. The median M2BPGi values were 0.26, 0.34, 0.57 and 1.21 cutoff index (COI), in liver histology with Ishak F0-1, F2, F3 and F4, respectively (p < 0.01). M2BPGi levels correlated with the Ishak scores (ρ = 0.312, p < 0.001). Using the cutoff values of 0.25, 0.45 and 0.96 COI for ≥F2, ≥F3 and F4, the AUROCs were 0.653, 0.795 and 0.914, respectively. Multivariate analysis with several other serum indices showed that M2BPGi was the most significant independent factor for ≥F3 (OR: 8.197, 95% CI: 2.699-24.897, p < 0.001). In patient subgroups with serial liver biopsies, both the proportion of F3/F4 and M2BPGi decreased at 1 year (8.3% vs. 2.8% and 0.32 vs. 0.21 COI, respectively; both p < 0.001). Histological fibrosis progression after ≥3 years of NA therapy accompanied with an increase in M2BPGi level, compared to patients without progression (+0.14 vs -0.03 COI, p = 0.045).

CONCLUSION

Serum M2BPGi is a reliable non-invasive marker for diagnosing ≥F2, ≥F3 and F4. It is the only significant marker for ≥F3 among several other indices. NA produced concordant dynamic changes in M2BPGi levels and histological fibrosis.

背景

Mac-2 结合蛋白糖基化异构体（M2BPGi）是一种新型的肝纤维化血清标志物，在慢性乙型肝炎（CHB）中研究较少。我们旨在评估其在诊断接受核苷（酸）类似物（NAs）治疗的 CHB 患者显著纤维化和肝硬化中的作用。

方法

招募了接受 NAs 治疗的 CHB 患者，这些患者在基线时进行了肝活检并可获得血清样本。在患者亚组中，在 1 年和 3 年时进行了配对的肝活检。

结果

共纳入 327 名接受 NAs 治疗的 CHB 患者（M:F=229:98；中位年龄 38.1 岁）。M2BPGi 值分别为 0.26、0.34、0.57 和 1.21 截距指数（COI），在肝组织学中分别为 Ishak F0-1、F2、F3 和 F4（p<0.01）。M2BPGi 水平与 Ishak 评分相关（ρ=0.312，p<0.001）。使用≥F2、≥F3 和 F4 的 0.25、0.45 和 0.96 COI 截断值，AUROCs 分别为 0.653、0.795 和 0.914。使用其他几种血清指标的多变量分析表明，M2BPGi 是≥F3 的最显著独立因素（OR：8.197，95%CI：2.699-24.897，p<0.001）。在具有系列肝活检的患者亚组中，1 年后 F3/F4 比例和 M2BPGi 均下降（8.3%比 2.8%和 0.32 比 0.21 COI，均 p<0.001）。与无进展患者相比，NA 治疗≥3 年后肝组织学纤维化进展伴有 M2BPGi 水平升高（+0.14 比 -0.03 COI，p=0.045）。