Serum Mac-2 Binding Protein Glycosylation Isomer Level Research Articles

MicroRNA-223-3p levels in serum-derived extracellular vesicles predict regression of M2BPGi-based liver fibrosis after hepatitis C virus eradication by direct-acting antiviral agents.

We retrospectively investigated microRNA (miRNA) levels in serum-derived extracellular vesicles (EVs) as predictive indicators for regression of liver fibrosis, after achievement of a sustained virological response (SVR) by direct-acting antiviral (DAA) therapy for chronic hepatitis C (CHC). The study subjects were recruited from a historical cohort of 108 CHC patients whose pretreatment serum Mac-2-binding protein glycosylation isomer (M2BPGi) levels were ≥ 2.0 cut-off index (COI). We classified patients with M2BPGi levels < 1.76 and ≥ 1.76 COI at 2 years after the end of treatment (EOT) into the regression and non-regression groups, respectively. Eleven of the patients were assigned to the discovery set, and we comprehensively investigated the miRNAs contained in serum-derived EVs at 24weeks after the EOT (EOT24W), using RNA sequencing. The remaining 97 patients were assigned to the validation set, and reproducibility was verified by quantitative real-time PCR. Through analysis of the discovery and validation sets, we identified miR-223-3p and miR-1290 as candidate predictors. Subsequently, we analyzed various clinical data, including these candidate miRNAs. Multivariate analyses revealed that the levels of miR-223-3p at EOT24W were significantly associated with regression of M2BPGi-based liver fibrosis (Odds ratio: 1.380; P = 0.024). Consistent results were obtained, even when the serum M2BPGi levels were aligned by propensity score matching and in patients with advanced M2BPGi-based liver fibrosis (pretreatment M2BPGi levels ≥ 3.3 COI). The miR-223-3p level in serum-derived EVs at EOT24W is a feasible predictor of regression of M2BPGi-based liver fibrosis after achievement of an SVR by DAA therapy.

Serum Mac-2 binding protein glycosylation isomer and galectin-3 levels in adult-onset Still's disease and their association with cytokines.

Autoinflammation with cytokine dysregulation may be implicated in the pathophysiology of adult-onset Still's disease (AOSD); however, the relationship between galectins and cytokines in patients with active AOSD remains unknown. We aimed to examine the relationship between circulating cytokines/chemokines and galectin-3 (Gal-3) or its ligand, Mac-2 binding protein glycosylation isomer (M2BPGi), in Japanese patients with AOSD. We recruited 44 consecutive patients diagnosed with AOSD according to the Yamaguchi criteria, 50 patients with rheumatoid arthritis (RA) as disease controls, and 27 healthy participants. Serum M2BPGi levels were directly measured using a HISCL M2BPGi reagent kit and an automatic immunoanalyzer (HISCL-5000). Serum Gal-3 concentrations were measured by enzyme-linked immunosorbent assay. The serum levels of 69 cytokines were analyzed in patients with AOSD using a multi-suspension cytokine array. We performed a cluster analysis of each cytokine expressed in patients with AOSD to identify specific molecular networks. Significant increases in the serum concentrations of Gal-3 and M2BPGi were found in the serum of patients with AOSD compared with patients with RA and healthy participants (both p <0.001). There were significant positive correlations between serum Gal-3 levels and AOSD disease activity score (Pouchot score, r=0.66, p <0.001) and serum ferritin levels. However, no significant correlations were observed between serum M2BPGi levels and AOSD disease activity scores (Pouchot score, r = 0.32, p = 0.06) or serum ferritin levels. Furthermore, significant correlations were observed between the serum levels of Gal-3 and various inflammatory cytokines, including interleukin-18, in patients with AOSD. Immunosuppressive treatment in patients with AOSD significantly reduced serum Gal-3 and M2BPGi levels (p = 0.03 and 0.004, respectively). Although both Gal-3 and M2BPGi were elevated in patients with AOSD, only Gal-3 was a useful biomarker for predicting disease activity in AOSD. Our findings suggest that circulating Gal-3 reflects the inflammatory component of AOSD, which corresponds to proinflammatory cytokine induction through inflammasome activation cascades.

Serum inducible protein 10kDa/C-X-C motif chemokine10 levels predict regression of M2BPGi-based liver fibrosis after hepatitisC virus eradication by direct-acting antiviral agents.

It is desirable to identify predictors of regression of liver fibrosis after achieving sustained virological response by anti-hepatitisC virus (anti-HCV) therapy. We retrospectively investigated the serum interferon-γ inducible protein 10kDa (IP-10) level as a predictive indicator of regression of liver fibrosis after successful hepatitis C virus eradication by direct-acting antiviral agents (DAAs) therapy. The study participants were recruited from a historical cohort of 116 chronically hepatitisC virus-infected patients who had achieved sustained virological response by DAAs therapy and whose serum Mac-2 binding protein glycosylation isomer (M2BPGi) levels at baseline (before DAAs therapy) were ≥2.0 cut-off index. We defined patients with M2BPGi levels <1.76 and ≥1.76 cut-off index at 2years after the end of treatment (EOT) as the regression (n=71) and non-regression (n=45) groups, respectively. Multivariate analyses revealed that the albumin-bilirubin score at baseline, and albumin-bilirubin score, Fibrosis-4 index at 24weeks after the EOT, and serum IP-10 change from baseline to 24weeks after the EOT (IP-10 change) were significantly associated with regression of M2BPGi-based liver fibrosis. In addition, IP-10 change was significantly associated with regression of M2BPGi-based liver fibrosis by a multivariate analysis, even when the serum M2BPGi levels were aligned by propensity score matching and in patients with advanced M2BPGi-based liver fibrosis: M2BPGi levels ≥3.3 cut-off index at baseline. Serum IP-10 change from baseline to 24weeks after the EOT is a feasible predictor of regression of M2BPGi-based liver fibrosis after achieving sustained virological response with DAA therapy.

Correlation of Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) with Liver Transient Elastography Results in Evaluating Liver Fibrosis in Chronic Hepatitis B Patients

Background: Hepatitis B virus (HBV) is a serious health problem in the world, including in Indonesia. Transient elastography (TE) is now regarded as a reliable surrogate marker for grading the severity of liver fibrosis in chronic hepatitis B (CHB) patients. The Mac-2 binding protein of glycosylation isomer (M2BPGi) is a novel non-invasive serum biomarker for liver fibrosis staging in various liver diseases including CHB. This study aims to evaluate the correlation of M2BPGi and liver stiffness (LS), measured through TE, in predicting liver fibrosis among CHB patients.Method: A cross-sectional study was conducted at Dr. Hasan Sadikinl General Hospital Bandung between September 2021–January 2022 on patients diagnosed with CHB based on clinical and biochemical examination. The subjects underwent TE examination using Fibroscan® and M2BPGi levels were determined with an automated immunoassay analyzer HISCL-800, Sysmex, Japan. Statistical analysis was conducted using the Spearman rank correlation method with a significance value of p 0.05.Results: A total of 119 CHB (M:F = 66:53, median age 43 years) patients were consecutively recruited. The median M2BPGi level was 1.04 COI (0.74–1.59) and the median of LS was 7.3 (5.6–12.5). M2BPGi had a moderate and significant correlation with LS (r = 0.525; p 0.001). Median M2BPGi values in each fibrosis stage were 0.89 COI in F0-F1, 0.88 in F2, 1.61 in F3, and 2.24 in F4 (p 0.001).Conclusion: This study revealed a moderate positive correlation between serum M2BPGi level and LS in CHB patients.

Diagnostic performance of Mac-2-binding protein glycosylation isomer (M2BPGi) as a liver fibrosis marker in chronic hepatitis C patients with chronic kidney disease on hemodialysis

Liver fibrosis assessment is essential to determine the initiation, duration, and evaluation of chronic hepatitis C treatment. Therefore, the study aimed to assess the role of Mac-2-binding protein glycosylation isomer (M2BPGi) as a biomarker to measure liver fibrosis in chronic hepatitis C patients with chronic kidney disease on hemodialysis. This study used a cross-sectional design. Serum M2BPGi level and transient elastography results were evaluated in 102 chronic hepatitis C patients with CKD on HD, 36 CKD on HD patients, and 48 healthy controls. ROC analysis was conducted to identify the optimal cutoff values to assess significant fibrosis and cirrhosis among chronic hepatitis C patients with CKD on HD. In chronic hepatitis C patients with CKD on HD, the level of serum M2BPGi had a moderately significant correlation with transient elastography (r = 0.447, p < 0.001). The median serum M2BPGi was higher among CKD on HD patients compared to healthy controls (1.260 COI vs. 0.590 COI, p < 0.001) and was even higher in chronic hepatitis C patients with CKD on HD compared to CKD on HD group (2.190 COI vs. 1.260 COI, p < 0.001). It is also increased according to the severity of liver fibrosis: 1.670 COI, 2.020 COI, and 5.065 COI for F0-F1, significant fibrosis, and cirrhosis, respectively. The optimal cutoff values for diagnosing significant fibrosis and cirrhosis were 2.080 and 2.475 COI, respectively. Serum M2BPGi could be a simple and reliable diagnostic tool for evaluating cirrhosis in chronic hepatitis C patients with CKD on HD.

Serum Mac-2 Binding Protein Glycosylation Isomer Concentrations Are Associated With Incidence of Type 2 Diabetes.

Serum Mac-2 binding protein glycosylation isomer (M2BPGi) concentrations are known to be an indicator of chronic liver injury and fibrosis. This study aimed to investigate the association between serum M2BPGi concentrations and the development of type 2 diabetes in a Japanese community. A total of 2143 community-dwelling Japanese individuals aged 40-79 years without diabetes at baseline were followed up for 7 years. Serum M2BPGi concentrations were divided into quintiles: Q1, ≤0.37 cutoff index (COI); Q2, 0.38-0.49 COI; Q3, 0.50-0.62 COI; Q4, 0.62-0.80 COI; and Q5, ≥0.81 COI. Cox proportional hazards models were used to estimate hazard ratios and 95% CIs for the development of type 2 diabetes. During the follow-up period, 219 individuals developed type 2 diabetes. The age- and sex-adjusted cumulative incidence of type 2 diabetes significantly increased with elevating serum M2BPGi levels (P for trend < .01). This association remained significant after adjustment for potential confounders (P for trend = .04). This significant association attenuated to a nonsignificant level after additionally adjusting for serum high-sensitivity C-reactive protein or homeostasis model assessment of insulin resistance. The present study demonstrated that higher serum M2BPGi concentrations were significantly associated with higher risk of diabetes in a Japanese community. Moreover, inflammation and insulin resistance were suggested to contribute to the excess risk of diabetes in individuals with higher serum M2BPGi levels. These findings shed light on the importance of inflammation and insulin resistance when considering the pathogenesis of diabetes.

Serum Mac-2 Binding Protein Glycosylation Isomer to Predict the Severity of Hepatic Fibrosis in Patients with Hepatitis C Virus Infection.

Large-scale studies to assess the utility of the Mac-2 binding protein glycosylation isomer (M2BPGi) in predicting hepatic fibrosis in patients with hepatitis C virus (HCV) infection are limited. Serum M2BPGi level determination was performed in 1460 patients with HCV who received liver stiffness measurement (LSM) using transient elastography (TE). The correlation of LSM and grade of hepatic fibrosis as staged by TE with M2BPGi was assessed. Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic power of M2BPGi for fibrosis stages of ≥F2, ≥F3, and F4. The selected M2BPGi cutoff values were chosen based on the maximal Youden index, a positive likelihood ratio (LR) ≥ 10, and a negative LR ≤ 0.1. Serum M2BPGi level was highly correlated with LSM (Pearson correlation coefficient: 0.567, p &lt; 0.001) and hepatic fibrosis stage (Spearman's rank correlation coefficient: 0.772, p &lt; 0.001). The areas under ROC curves (AUROCs) of M2BPGi for ≥F2, ≥F3, and F4 were 0.865 (95% confidence interval [CI]: 0.846-0.884), 0.937 (95 % CI: 0.922-0.952), and 0.962 (95% CI: 0.951-0.972). The maximal Youden indices for ≥F2, ≥F3, and F4 were 1.72, 2.65, and 3.93. By selecting M2BPGi cutoff values with a positive LR ≥ 10 and a negative LR ≤ 0.1, clinicians were able to correctly discriminate F2, F3, and F4 in 69.1%, 77.8%, and 90.1% of patients. In conclusion, serum M2BPGi is a good diagnostic tool to predict the severity of hepatic fibrosis in patients with HCV infection.

Mac-2-binding protein glycosylation isomer is useful to predict muscle cramps in patients with chronic liver disease.

Muscle cramps are frequently overlooked and worsen the quality of life in patients with chronic liver disease (CLD). Therefore, a valuable biomarker for predicting muscle cramps is required in the clinical setting. This study aimed to investigate whether the serum Mac-2-binding protein glycosylation isomer (M2BPGi) levels, a reliable liver fibrosis marker, could predict muscle cramps in patients with CLD. This retrospective study included 80 patients with CLD. Muscle cramps were assessed using a questionnaire regarding their presence, frequency, pain severity, and duration. The associated predictors were analyzed using logistic regression analysis. The diagnostic accuracy and optimal cutoff values were evaluated using receiver operating characteristic curves. Of the 80 patients, 55% had muscle cramps and showed significantly higher serum M2BPGi levels than those without them (4.54 cutoff index [COI] vs 2.20; P = .001). Multivariate analysis revealed that M2BPGi (odds ratio [ORs], 1.19; 95% confidence interval, 1.003–1.42; P = .046) was independently associated with the presence of muscle cramps. The optimal COI value for predicting muscle cramps was 3.95, and the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 61.4%, 80.6%, 79.4%, 63.0%, and 70.0%, respectively. Patients with a COI value ≥3.95 had a 2-fold higher incidence of muscle cramps than patients with a COI value <3.95 (79% vs 37%; P < .001). M2BPGi levels were also associated with the duration of muscle cramps. Serum M2BPGi appears useful as a biomarker for predicting muscle cramps in patients with CLD.

Clinical usefulness of Mac-2 binding protein glycosylation isomer for diagnosing liver cirrhosis and significant fibrosis in patients with chronic liver disease: A retrospective single-center study.

Accurate diagnosis of liver cirrhosis (LC) and significant fibrosis in patients with chronic liver disease (CLD) is important. The Mac-2 binding protein glycosylation isomer (M2BPGi) has emerged as a novel serum biomarker for liver fibrosis; however, insufficient clinical data of M2BPGi are available in patients with CLD. Therefore, we performed a retrospective cohort study to investigate the clinical usefulness of serum M2BPGi for assessing LC and significant fibrosis in CLD patients. We retrospectively reviewed the CLD patients with measured serum M2BPGi at Kosin University Gospel Hospital between January 2016 and December 2019. Multivariate logistic regression analyses were conducted to identify the independent factors associated with LC. The diagnostic power of serum M2BPGi for LC and significant fibrosis (≥F2) was evaluated and compared to that of other serum biomarkers using receiver operating characteristic curve and area under the curve (AUC). A total of 454 patients enrolled in this study. M2BPGi (adjusted odds ratio [aOR], 1.77; 95% confidence interval [CI], 1.52–2.07) and fibrosis index based on four factors (aOR, 1.23; 95% CI, 1.11–1.37) were identified as significant independent factors for LC. The AUC of M2BPGi for LC (0.866) and significant fibrosis (0.816) were comparable to those of fibrosis index based on four factors (0.860, 0.773), aspartate aminotransferase-to-platelet ratio index (0.806, 0.752), and gamma-glutamyl transpeptidase-to-platelet ratio (0.759, 0.710). The optimal cut-off values for M2BPGi for LC and significant fibrosis were 1.37 and 0.89, respectively. Serum M2BPGi levels were significantly correlated with liver stiffness measurements (ρ = 0.778). Serum M2BPGi is a reliable noninvasive method for the assessment of LC and significant fibrosis in patients with CLD.

Serum angiopoietin-2 levels predict regression of Mac-2 binding protein glycosylation isomer-based liver fibrosis after hepatitis C virus eradication by direct-acting antiviral agents.

It is desirable to identify predictors of regression of liver fibrosis after achieving a sustained virologic response (SVR) by direct-acting antiviral agents (DAAs) to antihepatitis C virus (HCV) therapy. Here, we retrospectively investigated the serum angiopoietin-2 (Ang-2) level as a predictive indicator of regression of liver fibrosis after successful HCV eradication by DAA therapy. The study subjects were recruited from a historical cohort of 109 chronically HCV-infected patients who had achieved SVR by DAA therapy and whose serum Mac-2 binding protein glycosylation isomer (M2BPGi) levels at baseline (before DAA therapy) were ≥2.0 the cut-off index (COI). We defined patients with M2BPGi levels <1.76 and≥1.76 COI at 2years after the end of treatment (EOT) as the regression (R, n=69) and nonregression (NR, n=40) groups, respectively. Multivariate analyses revealed that the Ang-2 level at baseline and the Ang-2 level, albumin-bilirubin score, and FIB-4 index at 24weeks after the EOT were significantly associated with regression of M2BPGi-based liver fibrosis. Receiver operating characteristic curve analyses showed that the Ang-2 level at 24weeks after the EOT had the largest area under the curve values (0.859). The same results were obtained even when the serum M2BPGi levels were aligned by propensity score matching and in patients with advanced M2BPGi-based liver fibrosis: M2BPGi levels ≥3.3 COI at baseline. The serum Ang-2 level at 24weeks after the EOT is a feasible predictor of regression of M2BPGi-based liver fibrosis after achieving SVR by DAA therapy.

Comparison of Mac‐2 binding protein glycosylation isomer (M2BPGi) with AST to platelet ratio index (APRI), fibrosis 4 Score (FIB‐4), and nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) for NAFLD patients

AbstractThe serum level of Mac‐2 binding protein glycosylation isomer (M2BPGi) has been found to increase with the severity of liver fibrosis in biopsy‐proved nonalcoholic fatty liver disease (NAFLD). However, the comparison of M2BPGi with noninvasive fibrosis markers such as AST to platelet ratio index (APRI), Fibrosis 4 Score (FIB‐4), and NAFLD fibrosis score (NFS) in NAFLD patients remains unclear. The participants of Tzu Chi NAFLD cohort (TCNC) including health controls or NAFLD patients were enrolled in Taipei Tzu Chi Hospital. NAFLD was defined as fatty liver in imaging without hepatitis B virus (HBV), hepatitis C virus (HCV), drug, alcohol, or other known causes of chronic liver disease. A total of 777 subjects were included for final analysis. The serum levels of M2BPGi correlated with APRI, FIB‐4 score, and NFS, respectively (P &lt; .001). Of them, 376 (48.4%) were NAFLD patients and 401 were healthy controls. In the group of health controls or NAFLD patients, the M2BPGi levels were significantly higher in female subjects than those of male subjects (P = .027 and 0.006, respectively). Categorized by age, the levels of M2BPGi were significantly higher in elder age groups either in healthy controls or NAFLD patients (P &lt; .05). Compared with healthy controls, NAFLD patients had significantly higher levels of BMI, waist circumference, metabolic components, and liver fibrosis markers such as APRI, NFS, and M2BPGi (P &lt; .05), but no difference in FIB‐4 score (P = .685). According to FIB‐4 score, “intermediate‐ or high‐risk group” had higher APRI, NFS, and M2BPGi than low‐risk group. The serum M2BPGi levels correlated with three noninvasive biomarkers of liver fibrosis including APRI, FIB‐4 score, and NFS. They were significantly higher in female or elder population. Furthermore, APRI, NFS, and M2BPGi were different between NAFLD patients and healthy controls, but no FIB‐4 score. According to FIB‐4 score to determine the risk of liver fibrosis, APRI, NFS, and M2BPGi were also different between low risk and “intermediate or high risk” of NAFLD patients, suggesting a surrogate marker for assessing liver fibrosis of NAFLD patients.

A prospective study of the correlation between hepatic fibrosis and noninvasively measured fibrosis markers including serum M2BPGi and acoustic radiation force impulse elastography

Background: Mac-2 binding protein glycosylation isomer (M2BPGi) was introduced as a noninvasively measurable serologic marker for liver fibrosis. Acoustic radiation force impulse imaging (ARFI) elastography is another noninvasive method of measuring hepatic fibrosis. There are limited data about the correlations between histologic fibrosis grade and noninvasively measured markers, including M2BPGi and ARFI.Methods: This prospective study was conducted among patients admitted consecutively for liver resection, cholecystectomy, or liver biopsy. ARFI elastography, serum M2BPGi levels, and the AST to Platelet Ratio Index (APRI) score were evaluated before histologic evaluation. Histologic interpretation was performed by a single pathologist using the METAVIR scoring system.Results: In patients with high METAVIR scores, M2BPGi levels and ARFI values showed statistically significant differences between patients with fibrosis and those without fibrosis. In 41 patients with hepatocellular carcinoma, as METAVIR scores increased, M2BPGi levels also tended to increase (p=0.161). ARFI values changed significantly as METAVIR scores increased (p=0.039). In 33 patients without hepatocellular carcinoma, as METAVIR scores increased, M2BPGi levels significantly increased (p=0.040). ARFI values also changed significantly as METAVIR scores increased (p=0.033). M2BPGi levels were significantly correlated with ARFI values (r=0.604, p&lt;0.001), and APRI values (r=0.704, p&lt;0.001), respectively. Conclusions: Serum M2BPGi levels increased with liver fibrosis severity and could be a good marker for diagnosing advanced hepatic fibrosis regardless of the cause of liver disease.

New sequential algorithm using Mac-2 binding protein glycosylation isomer to detect advanced carotid artery atherosclerosis

Although carotid artery sonography is widely performed, most guidelines do not recommend this procedure in the general population. Appropriate indications and effective algorithms are needed to detect advanced carotid artery atherosclerosis in a community setting. This study was designed as cross-sectional study. Adult subjects (n=228) who underwent a health check-up at our healthcare centre were included in the final analysis. Mac-2 binding protein glycosylation isomer (M2BPGi) quantification was based on a lectin antibody sandwich immunoassay. Subclinical atherosclerosis was diagnosed by carotid ultrasonography. The prevalence of subclinical atherosclerosis and advanced atherosclerosis was 37.2% (85/228) and 11.8% (27/228), respectively, in a community-based setting. Serum M2BPGi level was significantly higher in subjects with calcified plaque (0.6317) and luminal stenosis (0.6373) than in control groups (0.4913, all P<0.05). Pearson correlation analysis between M2BPGi and atherosclerotic cardiovascular disease (ASCVD) risk index (R=0.410, P<0.001) showed a positive relationship. The AUROC of serum M2BPGi for identifying calcified plaque or luminal stenosis was 0.679. The sequential algorithm using ASCVD and M2BPGi showed good negative predictive value (NPV) (93.6%) and reasonable positive predictive value (PPV) (53.8%) for identifying calcified plaque or luminal stenosis. When the sequential algorithm was used as an indicator for carotid ultrasonography, 35.0% (14/40) of subjects with intermediate-risk by ASCVD (≥7.5%) could avoid unnecessary carotid ultrasonography. The sequential algorithm using ASCVD (≥7.5) and M2BPGi (≥0.525) provided reasonable indication for carotid artery sonography in a community-based setting.

Serum levels of mac-2 binding protein are associated with diabetic microangiopathy and macroangiopathy in people with type 2 diabetes

IntroductionNon-alcoholic fatty liver disease is reportedly associated with type 2 diabetes and progressive liver fibrosis, as evaluated by transient elastography, and has been linked with micro- and macroangiopathy in people...

M2BPGi for assessing liver fibrosis in patients with hepatitis C treated with direct-acting antivirals.

BACKGROUNDAssessing liver fibrosis is important for predicting the efficacy of direct-acting antivirals (DAAs) and patient prognosis. Non-invasive techniques to assess liver fibrosis are becoming important. Recently, serum Mac-2 binding protein glycosylation isomer (M2BPGi) was identified as a non-invasive marker of liver fibrosis.AIMTo investigate the diagnostic accuracy of M2BPGi in assessing liver fibrosis in patients with chronic hepatitis C (CHC) treated with DAAs.METHODSFrom December 2017 to August 2018, 80 treatment-naïve adult patients with CHC who were eligible for DAAs therapy were consecutively enrolled in this observational cohort study. For 12 weeks, 65 patients were treated with sofosbuvir/daclatasvir, and 15 patients were treated with sofosbuvir/daclatasvir and a weight-based dose of ribavirin at knowledge and technology association for hepatitis C management clinic, Cairo, Egypt. We measured serum M2BPGi levels, PAPAS index, fibrosis-4 (FIB-4) score and liver stiffness measurements (LSM) at baseline and 12 weeks after the end of treatment. Serum M2BPGi levels were measured using enzyme-linked immunosorbent assay.RESULTSAll patients achieved sustained virologic response (SVR12) (100%). Serum M2BPGi levels, LSM, FIB-4 score and PAPAS index decreased significantly at SVR12 (P < 0.05). Serum M2BPGi levels correlated positively with LSM at baseline and SVR12 (P < 0.001). At baseline, compared with the FIB-4 score and PAPAS index, M2BPGi was the best marker to distinguish patients with grade F4 fibrosis (AUC = 0.801, P < 0.001), patients with grade F2 from grade F0-1 fibrosis (AUC = 0.713, P = 0.012), patients with grade F3-4 from grade F0-2 fibrosis (AUC = 0.730, P < 0.001), and patients with grade F2-4 from grade F0-1 fibrosis (AUC = 0.763, P < 0.001). At SVR12, M2BPGi had the greatest AUCs for differentiating patients with grade F4 fibrosis (AUC = 0.844, P < 0.001), patients with grade F3 from grade F0-2 fibrosis (AUC = 0.893, P = 0.002), patients with grade F3-4 from grade F0-2 fibrosis (AUC = 0.891, P < 0.001), and patients with grade F2-4 from grade F0-1 fibrosis (AUC = 0.750, P < 0.001).CONCLUSIONM2BPGi is a reliable marker for the non-invasive assessment and prediction of liver fibrosis regression in patients with CHC who achieved an SVR with DAAs therapy.

510-P: Serum Mac-2 Binding Protein Is Associated with Diabetic Micro- and Macroangiopathy in People with Type 2 Diabetes

A close relationship between type 2 diabetes and nonalcoholic fatty liver disease, including liver fibrosis, has been reported. Mac-2 binding protein glycosylation isomer (M2BPGi) is reported as a non-invasive new serological glyco-biomarker for liver fibrosis. The purpose of this cross-sectional study was to investigate the association between serum M2BPGi levels and diabetic complications in people with type 2 diabetes. Serum M2BPGi levels were measured in terms of cut-off index (C.O.I.) units. Urinary albumin excretion (UAE) was calculated and nephropathy was graded as normo-, micro-, or macroalbuminuria. Retinopathy was divided into three groups: no- (NDR), simple- (SDR), or proliferative diabetic retinopathy (PDR). Mean age for 363 people (212 males) was 66.4 (10.6) years, the median M2BPGi level was 0.77 (0.57-1.04) C.O.I., and the median UAE was 22 (9-82.1) mg/g Cr. Serum M2BPGi level was increased with levels of diabetic microangiopathy. Furthermore, the M2BPGi levels in people with a history of cardiovascular diseases were higher than that in people without (0.82 [0.65-1.22] vs. 0.76 [0.55-1.03] C.O.I., p = 0.019). The logarithm of M2BPGi was associated with the logarithm of UAE after adjusting for covariates (β = 0.107, p = 0.031). This study reveals a close association between serum M2BPGi levels and diabetic micro- and macroangiopathy in people with type 2 diabetes. Disclosure Y. Hashimoto: None. M. Hamaguchi: None. M. Fukui: None.

The Serum Mac-2-binding Protein Glycosylation Isomer Dynamics in Acute Liver Injury.

Objective We aimed to examine the dynamics of serum Wisteria floribunda agglutinin-positive human Mac-2-binding protein glycosylation isomer (M2BPGi) in patients with acute liver injury. Methods Serum M2BPGi levels at the time of the diagnosis (n=77) and normalization of the serum alanine aminotransferase (ALT) level (n=26) were examined retrospectively. The difference in the serum M2BPGi level according to the etiology, and the correlations with other laboratory parameters were evaluated. Results The serum M2BPGi level at the time of the diagnosis was increased in 59 of 77 patients [2.3 cutoff index (COI); range, 0.31-11.1 COI] and was significantly decreased at the time of serum ALT normalization (0.68 COI; range, 0.15-1.87 COI; p<0.0001). The serum M2BPGi level was positively correlated with the duration for which serum ALT normalization was achieved (n=46, Spearman rho=0.53, p<0.0001). A multivariate analysis identified total bilirubin (T-bil), albumin, ALT, alkaline phosphatase, and etiology (e.g., drug-induced liver injury or etiology unknown) as independent factors for increased serum M2BPGi. In patients with infectious mononucleosis, the serum M2BPGi level was higher relative to the degree of increase of serum ALT or T-bil levels in comparison to other etiologies. Conclusion The serum M2BPGi level in patients with acute liver injury reflects the magnitude and duration of liver injury. However, it should be noted that the degree of increase of serum M2BPGi in patients with acute liver injury may differ according to the etiology.

Diagnostic performance of Mac-2 binding protein glycosylation isomer (M2BPGi) in screening liver fibrosis in health checkups.

BackgroundMild‐to‐moderate fibrosis is rarely diagnosed because the disease is asymptomatic in the early stage. The serum level of Mac‐2 binding protein glycosylation isomer (M2BPGi) has been found to increase with the severity of liver fibrosis. The aim of this study was to determine the diagnostic performance of M2BPGi in screening liver fibrosis using magnetic resonance elastography (MRE) as a reference standard and to compare it with using the aspartate aminotransferase‐to‐platelet ratio (APRI) and the Fibrosis‐4 index (FIB‐4) in health checkups.MethodsThis cross‐sectional study consecutively selected subjects at health examinations who underwent MRE and M2BPGi testing at eight health promotion centers in Korea between January and September 2019. The serum M2BPGi level was measured using the chemiluminescence enzyme immunoassay method. The measured levels were indexed using the cutoff index (COI). COI values of M2BPGi were compared with the MRE results.ResultsThe median (interquartile) values of COI for fibrosis stages F0 (normal liver stiffness), F1 (mild fibrosis), F2 (significant fibrosis), and ≥F3 (advanced fibrosis) were 0.49 (0.34‐0.61), 0.48 (0.38‐0.68), 0.64 (0.43‐1.03), and 1.01 (0.75‐1.77), respectively (P < .0001). The AUCs of the COI for the screening of fibrosis stage ≥F1, ≥F2, and ≥F3 were 0.591, 0.698, and 0.853, respectively. Using a threshold of 0.75 for COI to exclude advanced fibrosis had a sensitivity, specificity, and negative predictive value of 80.0%, 77.9%, and 98.9%, respectively. The AUC for excluding advanced fibrosis was better for M2BPGi than for FIB‐4 and APRI.ConclusionSerum M2BPGi was useful for screening significant and advanced fibrosis in health checkups.

On-treatment Serum Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) Level and Risk of Hepatocellular Carcinoma Development in Patients with Chronic Hepatitis B during Nucleot(s)ide Analogue Therapy.

We aimed to analyze the serum level of a novel fibrosis marker, Mac-2-binding protein glycosylation isomer (M2BPGi), and its predictive value for hepatocellular carcinoma (HCC) development in chronic hepatitis B (CHB) under nucleot(s)ide analogue (NA) therapy. Serum M2BPGi levels were quantified in 147 CHB patients at baseline, 48 weeks after starting NA therapy, and at the patients’ last visit. The serum M2BPGi level serially decreased at each time point. During the median follow-up time of 6.6 years, 14 of 147 patients developed HCC. Multivariate Cox proportional hazard analysis demonstrated that high serum M2BPGi at 48 weeks was an independent risk factor for HCC development. A cutoff value of M2BPGi at 48 weeks > 1.5 showed an adjusted hazard ratio = 34.9 (95% confidence interval, 4.3–284.9). The 3- and 5-year cumulative incidence of HCC in patients with low M2BPGi were 0.9% and 4.2%, respectively, whereas those in patients with high M2BPGi were 10.1% and 25.6%, respectively (p < 0.001). In conclusion, Serum M2BPGi level at 48 weeks is a useful predictor for HCC development in patients with CHB who receive NA therapy.

Baseline Mac-2 Binding Protein Glycosylation Isomer Level Stratifies Risks of Hepatocellular Carcinoma in Chronic Hepatitis B Patients with Oral Antiviral Therapy

Background and Aims: Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel biomarker correlating with liver fibrosis stages. However, little is known about how it predicts risks of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients receiving long-term antiviral treatment. Materials and Methods: The study contained 2 parts. The first part was to explore whether M2BPGi could be an HCC predictor in 899 CHB patients receiving long-term entecavir therapy. The second part was to validate the findings in an independent cohort of 384 on-treatment CHB patients with more severe liver disease. Results: In the discovery cohort, there were 64 patients developing HCC within an average follow-up of 7.01 years. Our data showed that M2BPGi level was positively associated with HCC development. When stratifying the patients by an M2BPGi level of 1.73 (the third quartile), the high M2BPGi group was shown to have an increased HCC risk compared to the low M2BPGi group with hazard ratio of 5.80 (95% CI 3.50–9.60). Furthermore, we found that the M2BPGi level complements PAGE-B score, a well-validated HCC prediction model, to predict HCC development. Lastly, the cutoff was validated in the independent cohort, especially those with an intermediate PAGE-B score. Conclusions: In CHB patients receiving long-term antiviral treatment, serum M2BPGi level not only serves as an independent HCC predictor but also complements PAGE-B in stratifying HCC risks.