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慢性丙型肝炎肝损伤相关的血清细胞凋亡标志物:sFas 是儿童和成人肝纤维化的标志物,而 M30 仅与儿童重度脂肪变性相关。

Serum apoptosis markers related to liver damage in chronic hepatitis C: sFas as a marker of advanced fibrosis in children and adults while M30 of severe steatosis only in children.

机构信息

Laboratory of Molecular Biology, Pathology Division, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina.

出版信息

PLoS One. 2013;8(1):e53519. doi: 10.1371/journal.pone.0053519. Epub 2013 Jan 11.

Abstract

BACKGROUND

Liver biopsy represents the gold standard for evaluating damage and progression in patients with chronic hepatitis C (CHC); however, developing noninvasive tests that can predict liver injury represents a growing medical need. Considering that hepatocyte apoptosis plays a role in CHC pathogenesis; the aim of our study was to evaluate the presence of different apoptosis markers that correlate with liver injury in a cohort of pediatric and adult patients with CHC.

METHODS

Liver biopsies and concomitant serum samples from 22 pediatric and 22 adult patients with CHC were analyzed. Histological parameters were evaluated. In serum samples soluble Fas (sFas), caspase activity and caspase-generated neoepitope of the CK-18 proteolytic fragment (M30) were measured.

RESULTS

sFas was associated with fibrosis severity in pediatric (significant fibrosis p = 0.03, advanced fibrosis p = 0.01) and adult patients (advanced fibrosis p = 0.02). M30 levels were elevated in pediatric patients with severe steatosis (p = 0.01) while in adults no relation with any histological variable was observed. Caspase activity levels were higher in pediatric samples with significant fibrosis (p = 0.03) and they were associated with hepatitis severity (p = 0.04) in adult patients. The diagnostic accuracy evaluation demonstrated only a good performance for sFas to evaluate advanced fibrosis both in children (AUROC: 0.812) and adults (AUROC: 0.800) as well as for M30 to determine steatosis severity in children (AUROC: 0.833).

CONCLUSIONS

Serum sFas could be considered a possible marker of advanced fibrosis both in pediatric and adult patient with CHC as well as M30 might be a good predictor of steatosis severity in children.

摘要

背景

肝活检是评估慢性丙型肝炎(CHC)患者损伤和进展的金标准;然而,开发能够预测肝损伤的非侵入性测试是越来越大的医疗需求。鉴于肝细胞凋亡在 CHC 发病机制中起作用;我们的研究旨在评估在一组患有 CHC 的儿科和成年患者中与肝损伤相关的不同凋亡标志物的存在。

方法

分析了 22 例儿科和 22 例成年 CHC 患者的肝活检和同时采集的血清样本。评估了组织学参数。在血清样本中,测量了可溶性 Fas(sFas)、半胱天冬酶活性和半胱天冬酶生成的 CK-18 蛋白水解片段的新表位(M30)。

结果

sFas 与儿科(显著纤维化 p = 0.03,进展性纤维化 p = 0.01)和成年患者(进展性纤维化 p = 0.02)的纤维化严重程度相关。M30 水平在儿科患者严重脂肪变性时升高(p = 0.01),而在成年患者中,与任何组织学变量均无相关性。在具有显著纤维化的儿科样本中,半胱天冬酶活性水平较高(p = 0.03),并且与成年患者的肝炎严重程度相关(p = 0.04)。诊断准确性评估表明,sFas 仅对评估儿科(AUROC:0.812)和成年患者(AUROC:0.800)的进展性纤维化具有良好的性能,而 M30 可能是评估儿科患者脂肪变性严重程度的良好预测指标(AUROC:0.833)。

结论

血清 sFas 可被视为儿科和成年 CHC 患者进展性纤维化的可能标志物,而 M30 可能是预测儿童脂肪变性严重程度的良好指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b11b/3543432/551c2907c7d6/pone.0053519.g001.jpg

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