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治疗过程中血清槐凝集素阳性 Mac-2 结合蛋白的变化与慢性乙型肝炎患者接受干扰素α附加治疗后肝纤维化的消退有关。

On-treatment changes of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein are associated with the regression of liver fibrosis in chronic hepatitis B patients on interferon α add-on therapy.

机构信息

Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis & National Clinical Research Center of Digestive Diseases, Beijing, China.

Key Laboratory of Systems Biomedicine Ministry of Education, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.

出版信息

J Med Virol. 2019 Aug;91(8):1499-1509. doi: 10.1002/jmv.25465. Epub 2019 Apr 16.

Abstract

Wisteria floribunda agglutinin-positive Mac-2-binding protein (M2BP) has been identified as a predictor for the response of interferon α (IFN-α) in patients with viral hepatitis. However, whether serum glycosylation isomer of M2BP (M2BPGi) was associated with the regression of liver fibrosis in patients with chronic hepatitis B (CHB) during IFN-α add-on therapy is still unknown. CHB patients were treated with entecavir for 26 weeks followed by entecavir plus pegylated IFN-α for 52 weeks. Liver biopsies were taken at baseline and treatment week 78. The regression of fibrosis was identified according to Ishak standard or Ishak plus Progressive-Indeterminate-Regressive (P-I-R) standard. Serum M2BPGi and liver function tests were measured at baseline and every 26 weeks of treatment. A total of 72 CHB patients were included in the present study. Serum M2BPGi was correlated with fibrosis and necroinflammation both at baseline and week 78. If Ishak standard was used as the reference, only the percent change of M2BPGi at week 52 from week 26 (Δ%M2BPGi ) was independently associated with fibrosis regression at treatment week 78, the area under the ROC curve (AUROC) of Δ%M2BPGi for predicting fibrosis regression was 0.705. As for Ishak plus P-I-R standard, the AUROC of the predictive model for fibrosis regression (0.896M2BPGi  + 0.363necroinflammation score  + 2.051*Ishak score  - 4.489) was 0.888. These data indicated that dynamic changes of serum M2BPGi were associated with fibrosis regression in CHB patients on IFN-α add-on therapy.

摘要

紫藤凝集素阳性 Mac-2 结合蛋白(M2BP)已被确定为预测病毒肝炎患者对干扰素 α(IFN-α)反应的指标。然而,在 IFN-α 附加治疗中,慢性乙型肝炎(CHB)患者血清 M2BP 的糖基化异构体(M2BPGi)是否与肝纤维化消退相关尚不清楚。CHB 患者接受恩替卡韦治疗 26 周,然后接受恩替卡韦加聚乙二醇干扰素-α治疗 52 周。在基线和治疗第 78 周时进行肝活检。根据 Ishak 标准或 Ishak 加进展性-不确定-退行性(P-I-R)标准确定纤维化的消退。在基线和治疗的每 26 周时测量血清 M2BPGi 和肝功能检查。本研究共纳入 72 例 CHB 患者。基线和第 78 周时,血清 M2BPGi 与纤维化和坏死性炎症均相关。如果以 Ishak 标准为参考,只有第 52 周时与第 26 周相比 M2BPGi 的百分比变化(Δ%M2BPGi)与第 78 周时的纤维化消退独立相关,ROC 曲线下面积(AUROC)为 0.705。对于 Ishak 加 P-I-R 标准,纤维化消退预测模型的 AUROC(0.896M2BPGi + 0.363坏死性炎症评分+2.051*Ishak 评分-4.489)为 0.888。这些数据表明,在 IFN-α 附加治疗中,CHB 患者血清 M2BPGi 的动态变化与纤维化消退相关。

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