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.

Scientific reports 2020 Jan 15

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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.

Citation

Koji Ogawa, Takashi Kobayashi, Jun-Ichi Furukawa, Hisatoshi Hanamatsu, Akihisa Nakamura, Kazuharu Suzuki, Naoki Kawagishi, Masatsugu Ohara, Machiko Umemura, Masato Nakai, Takuya Sho, Goki Suda, Kenichi Morikawa, Masaru Baba, Ken Furuya, Katsumi Terashita, Tomoe Kobayashi, Manabu Onodera, Takahiro Horimoto, Keisuke Shinada, Seiji Tsunematsu, Izumi Tsunematsu, Takashi Meguro, Tomoko Mitsuhashi, Megumi Hato, Kenichi Higashino, Yasuro Shinohara, Naoya Sakamoto. 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. Scientific reports. 2020 Jan 15;10(1):321