Tri-antennary tri-sialylated mono-fucosylated glycan of alpha-1 antitrypsin as a non-invasive biomarker for non-alcoholic steatohepatitis: a novel glycobiomarker for non-alcoholic steatohepatitis
Tri-antennary tri-sialylated mono-fucosylated glycan of alpha-1 antitrypsin as a non-invasive biomarker for non-alcoholic steatohepatitis: a novel glycobiomarker for non-alcoholic steatohepatitis
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DOI：
10.1038/s41598-019-56947-1
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发表时间：
2020-01-15
影响因子：
4.6
通讯作者：
Sakamoto, Naoya
中科院分区：
文献类型：
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作者：
Ogawa, Koji;Kobayashi, Takashi;Sakamoto, Naoya
非酒精性脂肪性肝炎（NASH）是一种进行性形式的非酒精性脂肪性肝病（NAFLD），可能导致肝硬化或肝细胞癌。在这里，我们检查了三触角三唾液酸化单岩藻糖基化α-1抗胰蛋白酶聚糖（AAT-A3 F）的诊断效用，AAT-A3 F是在先前NASH诊断研究中鉴定的非侵入性糖生物标志物。这项研究包括131例经活检证实的日本NAFLD患者。我们评估AAT-A3 F在NASH诊断中的效用，并进行遗传分析以分析NASH中AAT-A3 F升高的机制。NASH患者的血清AAT-A3 F浓度显著高于NAFL患者，以及纤维化、小叶炎症和气球样变患者。肝脏FUT 6基因表达在NASH中显著高于NAFL。IL-6在NASH中的表达水平显著高于NAFL，并与FUT 6表达水平呈正相关。血清AAT-A3 F水平与肝脏FUT 6表达水平密切相关。在NAFLD患者中，AAT-A3 F水平随着纤维化、病理性炎症和气球样变而增加，并且可能有助于从纤维化的早期阶段非侵入性诊断NASH。
Non-alcoholic steatohepatitis (NASH) is a progressive form of non-alcoholic fatty liver disease (NAFLD) that may lead to liver cirrhosis or hepatocellular carcinoma. Here, we examined the diagnostic utility of tri-antennary tri-sialylated mono-fucosylated glycan of alpha-1 antitrypsin (AAT-A3F), a non-invasive glycobiomarker identified in a previous study of NASH diagnosis. This study included 131 biopsy-proven Japanese patients with NAFLD. We evaluated the utility of AAT-A3F in NASH diagnosis, and conducted genetic analysis to analyse the mechanism of AAT-A3F elevation in NASH. Serum AAT-A3F concentrations were significantly higher in NASH patients than in NAFL patients, and in patients with fibrosis, lobular inflammation, and ballooning. Hepatic FUT6 gene expression was significantly higher in NASH than in NAFL. IL-6 expression levels were significantly higher in NASH than in NAFL and showed a positive correlation with FUT6 expression levels. The serum-AAT-A3F levels strongly correlated with hepatic FUT6 expression levels. AAT-A3F levels increased with fibrosis, pathological inflammation, and ballooning in patients with NAFLD and may be useful for non-invasive diagnosis of NASH from the early stages of fibrosis.