Diagnostic Efficacy of Serum Mac-2 Binding Protein Glycosylation Isomer and Other Markers for Liver Fibrosis in Non-Alcoholic Fatty Liver Diseases.

Original Article Diagnostic Immunology CROSSMARK_logo_3_Test 1/1 Ann Lab Med 2021;41:302-309 https://doi.org/10.3343/alm.2021.41.3.302 ISSN 2234-3806 • eISSN 2234-3814 https://crossmark-cdn.crossref.org/widget/v2.0/logos/CROSSMARK_Color_square.svg 2017-03-16 Diagnostic Efficacy of Serum Mac-2 Binding Protein Glycosylation Isomer and Other Markers for Liver Fibrosis in Non-Alcoholic Fatty Liver Diseases Se Young Jang , M.D.1, Won Young Tak , M.D.1, Soo Young Park , M.D.1, Young-Oh Kweon , M.D.1, Yu Rim Lee , M.D.1, Gyeonghwa Kim , Ph.D.2, Keun Hur , Ph.D.2, Man-Hoon Han , M.D.3, and Won Kee Lee , Ph.D.4 Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Korea; 2Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea; 3Department of Pathology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Korea; 4Department of Medical Informatics, School of Medicine, Kyungpook National University, Daegu, Korea 1 Background: Mac-2 binding protein glycosylation isomer (M2BPGi) has been established as a non-invasive biomarker for liver fibrosis. We evaluated the diagnostic efficacy of M2BPGi compared with those of other liver fibrosis markers in liver fibrosis in non-alcoholic fatty liver disease (NAFLD). Methods: We analyzed serum M2BPGi levels in 113 NAFLD patients. A pathologist graded liver fibrosis histopathologically. The diagnostic efficacies of serum M2BPGi and other liver fibrosis markers (aspartate aminotransferase to platelet ratio index, fibrosis index based on four factors, and NAFLD fibrosis score [NFS]) were evaluated using correlation, area under the ROC curve (AUC), logistic regression, and C-statistics. Results: Serum M2BPGi level and other liver fibrosis markers showed a moderate correlation with fibrosis grade. The AUC values of M2BPGi were 0.761, 0.819, 0.866, and 0.900 for diagnosing fibrosis (F) > 0, F > 1, F > 2, and F > 3, respectively. Logistic regression analysis showed M2BPGi as the only independent factor associated with F > 2 and F > 3. Although C-statistics showed that NFS was the best diagnostic factor for F > 2 and F > 3, M2BPGi with NFS had an increased C-statistics value, indicating that it is a better diagnostic model. Conclusions: The serum M2BPGi level increased with liver fibrosis severity and could be a good biomarker for diagnosing advanced fibrosis and cirrhosis in NAFLD patients. A well-controlled, prospective study with a larger sample size is needed to validate the diagnostic power of M2BPGi and other fibrosis markers in NAFLD. Key Words: Mac-2 binding protein glycosylation isomer, Non-alcoholic fatty liver disease, Liver fibrosis, Diagnosis, Biomarker INTRODUCTION Serum Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel glyco-biomarker of liver fibrosis. Wisteria floribunda agglutinin-positive Mac-2 binding protein (M2BP) is converted into 302  www.annlabmed.org Received: June 2, 2020 Revision received: July 23, 2020 Accepted: November 30, 2020 Corresponding author: Won Young Tak, M.D., Ph.D. Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, 130 Dongdeok-ro, Jung-gu, Daegu 41944, Korea Tel: +82-53-200-5519 Fax: +82-53-426-2046 E-mail: © Korean Society for Laboratory Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. M2BPGi under liver fibrosis conditions. M2BPGi formation indicates changes in the sugar chain structure of M2BP and is correlated with the onset of liver fibrosis. M2BPGi has also been used as a serum biomarker for predicting the development of hepatocellular carcinoma (HCC) in patients with chronic hepatihttps://doi.org/10.3343/alm.2021.41.3.302 Jang SY, et al. Diagnostic efficacy of M2BPGi in NAFLD tis B [1, 2], chronic hepatitis C [3], or non-alcoholic fatty liver disease (NAFLD) [4]. Moreover, it can be used as a serum biomarker for diagnosing liver fibrosis in patients with viral hepatitis, autoimmune hepatitis [5], primary biliary cholangitis [6, 7], or NAFLD [8, 9]. The studies reporting these findings mainly involved Japanese patients; therefore, the applicability of serum M2BPGi level as a biomarker was recently validated in the Korean population [10-13]. NAFLD is an emerging condition worldwide. In recent years, NAFLD has become a highly prevalent form of liver disease and is a significant risk factor for the development of HCC in most developed countries [14-16]. NAFLD can progress to liver cirrhosis owing to sustained liver injury and restoration, which lead to distortion of the hepatic architecture and progressive hepatic fibrosis. Liver cirrhosis increases the risk of developing HCC, impairs the immune system by reducing complement levels, and deteriorates the quality of life in cases involving ascites, variceal bleeding, or encephalopathy. Therefore, evaluating the extent and degree of liver fibrosis is essential for predicting the clinical outcomes of patients with NAFLD. Liver biopsy is the gold standard for evaluating liver fibrosis. However, liver biopsy is invasive, expensive, and susceptible to sampling errors, and it does not reflect the state of the whole liver [17]. Currently, transient elastography (TE; FibroScan, Echosens, Paris, France) and magnetic resonance elastography (MRE) are used to noninvasively evaluate liver fibrosis in patients with NAFLD. Other measures used in clinical practice include scoring models, such as aspartate aminotransferase (AST) to platelet ratio index (APRI), fibrosis index based on four factors (FIB-4), and NAFLD fibrosis score (NFS). We analyzed the diagnostic efficacy of serum M2B PGi compared with other markers in liver fibrosis in NAFLD. Kyungpook National University Hospital (KNUH-2017-10-031). All patients provided informed consent prior to liver biopsy and sample collection. MATERIALS AND METHODS Clinical and laboratory data Patients We included 113 patients who had undergone liver biopsy and were diagnosed as having NAFLD between March 2015 and March 2018 at Kyungpook National University Hospital, Daegu, Korea in this retrospective study. We excluded patients who consumed significant amounts of alcohol or had coexisting chronic liver diseases caused by hepatitis viruses. Routine biochemistry analyses, including liver function test and analyses of the lipid profile and complete blood count, were performed within a week before liver biopsy. This study was conducted according to local ethical guidelines, in accordance with the Declaration of Helsinki, 2013, and was approved by the Institutional R (...truncated)