Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgical Science, Gunma University, Graduate School of Medicine, 3-39-22 Showa Machi, Maebashi, Gunma, 371-8511, Japan.
Department of Surgery and Science, Kyushu University, Graduate School of Medicine, Fukuoka, Fukuoka, Japan.
J Gastroenterol. 2018 Jul;53(7):819-826. doi: 10.1007/s00535-017-1425-z. Epub 2018 Jan 9.
Assessing liver fibrosis is important for predicting the efficacy of antiviral therapy and patient prognosis. Liver biopsy is the gold standard for diagnosing liver fibrosis, despite its invasiveness and problematic diagnostic accuracy. Although noninvasive techniques to assess liver fibrosis are becoming important, reliable serum surrogate markers are not available. A glycoproteomics study aimed at identifying such markers discovered Mac 2-Binding Protein Gylcan Isomer (M2BPGi), which is a reliable marker for assessing liver fibrosis in patients with viral hepatitis and other fibrotic liver diseases such as primary biliary cholangitis, biliary atresia, autoimmune hepatitis, and nonalcoholic fatty liver disease. M2BPGi predicts the development of hepatocellular carcinoma (HCC) in patients infected with hepatitis B and C as well as the prognosis of liver cirrhosis in those with HCC after therapy. The unique features of M2BPGi are as follows: (1) cut-off values differ for the same stages of fibrosis according to the cause of fibrosis; and (2) M2BPGi levels rapidly decrease after patients achieve a sustained antiviral response to hepatitis C virus. These observations cannot be explained if M2BPGi levels reflect the amount of fibrotic tissue. Hepatic stellate cells (HSCs) secrete M2BPGi, which may serve as a messenger between HSCs and Kupffer cells via Mac-2 (galectin 3) that is expressed in Kupffer cells during fibrosis progression. Here we show that M2BPGi is a surrogate marker for assessing HSC activation. These findings may reveal the roles of HSCs in extrahepatic fibrotic disease progression.
评估肝纤维化对于预测抗病毒治疗的疗效和患者预后非常重要。肝活检是诊断肝纤维化的金标准，但存在侵袭性和诊断准确性问题。尽管评估肝纤维化的非侵入性技术变得越来越重要，但可靠的血清替代标志物尚未问世。一项旨在寻找此类标志物的糖蛋白质组学研究发现了 Mac 2-结合蛋白聚糖异构酶（M2BPGi），它是评估病毒性肝炎和原发性胆汁性胆管炎、胆道闭锁、自身免疫性肝炎和非酒精性脂肪性肝病等其他纤维性肝病患者肝纤维化的可靠标志物。M2BPGi 可预测乙型肝炎和丙型肝炎感染患者发生肝细胞癌（HCC）以及 HCC 患者经治疗后肝硬化的预后。M2BPGi 的独特之处在于：（1）根据纤维化的原因，相同纤维化阶段的截断值不同；（2）丙型肝炎病毒患者获得持续抗病毒应答后，M2BPGi 水平迅速下降。如果 M2BPGi 水平反映纤维组织的量，则无法解释这些观察结果。肝星状细胞（HSCs）分泌 M2BPGi，它可能通过在纤维化进展过程中在枯否细胞中表达的 Mac-2（半乳糖凝集素 3）在 HSCs 和枯否细胞之间充当信使。在这里，我们表明 M2BPGi 是评估 HSC 激活的替代标志物。这些发现可能揭示了 HSCs 在肝外纤维性疾病进展中的作用。
