Nouso Kazuhiro, Furubayashi Yoshie, Kariyama Kazuya, Wakuta Akiko, Miyake Nozomi, Inoue Kanae, Nagai Yuta, Murakami Shiho, Adachi Takuya, Oyama Atsushi, Wada Nozomu, Takeuchi Yasuto, Sakata Masahiro, Yasunaka Tetsuya, Onishi Hideki, Shiraha Hidenori, Takaki Akinobu, Shiota Shohei, Yasuda Satoshi, Toyoda Hidenori, Kawanaka Miwa, Kumada Takashi, Okada Hiroyuki
Department of Gastroenterology, Okayama City Hospital, Okayama, Japan.
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Hepatol Res. 2021 May;51(5):548-553. doi: 10.1111/hepr.13626. Epub 2021 Mar 19.
Nonalcoholic steatohepatitis (NASH) is a risk factor for nonvirus-related hepatocellular carcinoma, which is increasing in prevalence. The aim of this study was to clarify the clinical application of fucosylated alpha-fetoprotein (AFP-L3) in the process of nonalcoholic fatty liver (NAFL) disease development.
Serum samples from 115 diabetes mellitus (DM), 36 NAFL, and 119 NASH patients were analyzed for AFP-L3 expression using raw data of a micro total analysis system. These data were then compared with the clinical characteristics of the patients. A validation study was also undertaken with 55 samples (17 NAFL and 38 NASH).
Trace amounts of AFP-L3 were detected in 3.5%, 16.7%, and 58.0% of patients with DM, NAFL, and NASH, respectively. The odds ratio of AFP-L3 positivity for the diagnosis of NASH in multivariate analysis was 9.81 (95% confidence interval, 3.77-25.5). The rates in patients without fibrosis or with stage 1, stage 2, stage 3, and stage 4 fibrosis were 14.7%, 31.3%, 63.0%, 86.2%, and 100%, respectively. The rates were significantly increased according to the advancement of liver fibrosis (p < 0.001); however, no difference in the positive rate of AFP-L3 was observed between patients with and without fatty livers and between patients with normal and abnormal transaminase. The same relationship was also observed in the validation cohort.
Abnormal fucosylation of AFP occurred in patients with NASH, so it could be useful for the screening of NASH in patients with DM, as well as for the differential diagnosis of NASH and the evaluation of fibrosis.
非酒精性脂肪性肝炎（NASH）是非病毒相关肝细胞癌的一个危险因素，其患病率正在上升。本研究的目的是阐明岩藻糖化甲胎蛋白（AFP-L3）在非酒精性脂肪性肝病（NAFL）疾病发展过程中的临床应用。
使用微量全分析系统的原始数据分析115例糖尿病（DM）患者、36例NAFL患者和119例NASH患者的血清样本中AFP-L3的表达。然后将这些数据与患者的临床特征进行比较。还对55个样本（17例NAFL和38例NASH）进行了验证研究。
DM患者、NAFL患者和NASH患者中分别有3.5%、16.7%和58.0%检测到微量AFP-L3。多因素分析中AFP-L3阳性对NASH诊断的比值比为9.81（95%置信区间，3.77-25.5）。无纤维化或纤维化1期、2期、3期和4期患者的比例分别为14.7%、31.3%、63.0%、86.2%和100%。随着肝纤维化进展，该比例显著增加（p<0.001）；然而，有脂肪肝和无脂肪肝患者之间以及转氨酶正常和异常患者之间AFP-L3阳性率无差异。在验证队列中也观察到了相同的关系。
NASH患者中发生了AFP的异常岩藻糖化，因此它可用于DM患者中NASH的筛查，以及NASH的鉴别诊断和纤维化评估。
