纤连蛋白预测慢性乙型肝炎的血清清除率

StephenW

June 13, 2019
Fibronectin Predicts Seroclearance in Chronic Hepatitis B
Zahra Masoud

Fibronectin may be a potential marker for hepatitis B surface antigen (HBsAg) seroclearance, according to study results published in The Journal of Infectious Diseases.

A potentially achievable treatment end point for chronic hepatitis B viral (HBV) infection is seroclearance of HBsAg. Achieving this reflects a functional cure by indicating successful immune control of the infection. Although the kinetics of HBsAg serum and HBV DNA levels have been shown to be associated with HBsAg seroclearance, the clinicopathologic mechanisms leading to HBsAg seroclearance, and whether certain plasma proteins promote seroclearance is still uncertain. Therefore, the study aimed to apply isobaric tags for relative and absolute quantification-based quantitative proteomics to reveal protein profiles associated with HbsAg seroclearance, followed by validation and prediction of identified proteins in patient cohorts.

The study design included 3 stages: (1) isobaric tags-based proteomic analysis, (2) prospective validation in a separate cohort of 90 patients, and (3) an assessment of predictive values of identified plasma proteins for HBsAg seroclearance (n=164). For the first 2 stages, patients with chronic HBV infection who have never received treatment and prior HBsAg-positivity for at least 6 months were recruited for the study. These patients were either in the experimental group, which included patients with spontaneous HBsAg seroclearance, or the control group, which included patients with persistent HBsAg-positivity. HBsAg seroclearance was defined as serum HBsAg-negative results on 2 occasions that were at least 6 months apart and remaining negative up to the last visit. The experimental and control groups were age- and gender-matched.

In the first stage, proteomic analysis identified 487 plasma proteins, in which 97 of the proteins showed altered expression. Of these, 88 were upregulated and 9 were down-regulated. The 4 proteins that were most associated with immunologic response were fibronectin, CD44, aldolase A, and S100 calcium-binding protein A9.

In the second stage, 90 patients (45 in both the experimental and control groups) were studied. Median fibronectin levels were higher in patients achieving HBsAg seroclearance compared with HBsAg-positive control patients (P =.009). However, there were no significant differences in median levels of CD44, aldolase A, and S100 calcium-binding protein A9.

In the third stage, 164 patients (82 in both the experimental and control groups) had archived plasma at the 3 specific time points examined. Results showed that median fibronectin levels were higher in patients with HBsAg compared with control participants at Year −1 and Year 0 (both P <.001); however there was no significant difference at Year 3. Further, in the experimental group, there was no difference between median fibronectin levels across all 3 time points (P =.667), while a significant difference was observed in the control group (P <.001).

The predictive value of fibronectin was assessed at 3 years, 1 year before the time of HBsAg seroclearance (Year −1), and at the time of HbsAg seroclearance (Year 0).  In a subgroup of patients with annual HBsAg log reduction >0.5 (n=60), the addition of plasma fibronectin level at Year −1 achieved the highest predictive value (area under the receiving operating characteristic, 0.884; P =.0003). The optimal cutoff fibronectin level was 122.03 µg/mL, with a positive predictive value of 98.2% and a negative predictive value of 75.0%. Therefore, plasma fibronectin level was associated with HBsAG seroclearance and shows potential to be a predictor of “functional cure.”

Overall, the study authors concluded that, “Future studies should explore the mechanistic nature between fibronectin and HBsAg seroclearance, as well as its application in clinical prognostication of [chronic hepatitis B].”

Reference

Liu F, Seto W, Wong DK, et al. Plasma fibronectin levels identified via quantitative profiling predicts hepatitis B surface antigen seroclearance in chronic hepatitis B [published online May 6, 2019]. Journ Inf Dis. doi:10.1093/infdis/jiz223/5485908

StephenW

2019年6月13日
纤连蛋白预测慢性乙型肝炎的血清清除率
扎赫拉马苏德

根据发表在“传染病杂志”上的研究结果，纤连蛋白可能是乙型肝炎表面抗原（HBsAg）血清清除的潜在标志物。

慢性乙型肝炎病毒（HBV）感染的潜在可治疗终点是HBsAg的血清清除率。实现这一目标反映了通过表明感染的成功免疫控制的功能性治愈。与HBsAg血清清除相关，导致HBsAg血清清除的临床病理学机制，以及某些血浆蛋白是否促进血清清除尚不确定。该研究旨在应用同量异位标签进行基于相对和绝对定量的定量蛋白质组学，以揭示与HbsAg血清清除相关的蛋白质谱，然后验证和预测患者队列中已鉴定的蛋白质。

研究设计包括3个阶段：（1）基于同量异位标签的蛋白质组学分析，（2）90名患者的单独队列中的前瞻性验证，和（3）HBsAg血清清除的已鉴定血浆蛋白的预测值评估（n） = 164对于前2个阶段，招募了从未接受过治疗和既往HBsAg阳性至少6个月的慢性HBV感染患者，这些患者要么在实验组，其中包括自发性HBsAg血清清除患者HBsAg血清清除定义为2次血清HBsAg阴性结果，至少相隔6个月，并且在最后一次就诊时仍为阴性。实验组和对照组年龄和性别匹配。

与免疫应答最相关的4种蛋白质是纤连蛋白，CD44，醛缩酶A和S100钙结合蛋白A9。

在第二阶段，研究了90名患者（实验组和对照组均为45名）。与HBsAg阳性对照组患者相比，达到HBsAg血清清除率的患者中位纤连蛋白水平更高（P = .009）。然而，CD44，醛缩酶A和S100钙结合蛋白A9的中值水平没有显着差异。

在第三阶段，164名患者（实验组和对照组中的82名）在检查的3个特定时间点存档血浆。结果显示，与对照组相比，HBsAg患者的纤维连接蛋白中位数水平高于1年级和0年级（均P <.001）;然而，在第3年没有显着差异。此外，在实验组中，在所有3个时间点中间纤连蛋白水平之间没有差异（P = .667），而在对照组中观察到显着差异（P < .001）。

纤维连接蛋白的预测值在3年，HBsAg血清清除前1年（第-1年）和HbsAg血清清除时间（0年）时进行评估。在年度HBsAg对数减少> 0.5（n = 60）的患者亚组中，在-1岁时血浆纤连蛋白水平的增加达到最高预测值（接受操作特征下的面积，0.884; P = .0003）。最佳截断纤连蛋白水平为122.03μg/ mL，阳性预测值为98.2％，阴性预测值为75.0％。因此，血浆纤连蛋白水平与HBsAG血清清除率相关，并显示出可能成为“功能性治愈”的预测因子。

总体而言，该研究的作者得出结论：“未来的研究应该探讨纤维连接蛋白和HBsAg血清清除之间的机制性质，以及它在[慢性乙型肝炎]临床预后中的应用。”

参考

Liu F，Seto W，Wong DK，et al。通过定量分析鉴定的血浆纤连蛋白水平预测慢性乙型肝炎中的乙型肝炎表面抗原血清清除[在线发表于2019年5月6日]。 Journ Inf Dis。 doi：10.1093 / infdis / jiz223 / 5485908