Serum Mac-2 Binding Protein Glycosylation Isomer Research Articles

The value of serum Mac-2 binding protein glycosylation isomer in the diagnosis of liver fibrosis: a systematic review and meta-analysis

BackgroundThe early detection and intervention of liver fibrosis (LF) in patients with chronic liver disease is critical to their management. The accuracy of serum Mac-2 binding protein glycosylation isomer (M2BPGi) in the diagnosis of LF remains controversial. This study aimed to comprehensively assess the value of serum M2BPGi in diagnosing LF.MethodsThe PubMed, Embase, MEDLINE, Web of Science, and Cochrane Library databases were searched. The effect values were combined using a random-effects model. Meta-regression and subgroup analysis were used to explore the sources of heterogeneity. In addition, publication bias assessment and sensitivity analysis were conducted.ResultsThis study includes 12 studies with 2,416 patients. The pooled sensitivity, specificity, and AUROC of M2BPGi in the diagnosis of significant fibrosis (≥F2) were 0.65 (95% CI: 0.57–0.71), 0.79 (95% CI: 0.72–0.84), and 0.78 (95% CI: 0.74–0.81), respectively, while those for predicting extensive fibrosis (≥F3) were 0.76 (95% CI: 0.71–0.80), 0.75 (95% CI: 0.68–0.81), and 0.81 (95% CI: 0.77–0.84). Sensitivity analysis indicated stable results in this study. The disease type, cut-off values, study country, average age, and male proportion were the sources of heterogeneity in diagnosing significant fibrosis of M2BPGi (p < 0.05). Sample size, disease type, study country, publication year, cut-off values, average age, and male proportion were important sources of heterogeneity in diagnosing extensive fibrosis (p < 0.05).ConclusionSerum M2BPGi has good diagnostic performance for significant fibrosis and extensive fibrosis in patients with chronic hepatitis B (CHB), chronic hepatitis C (CHC), or nonalcoholic fatty liver disease (NAFLD) and is an effective, non-invasive, and convenient marker.Systematic Review Registrationhttps://inplasy.com/inplasy-2023-10-0086/.

Serum Mac-2 binding protein glycosylation isomer dynamics in patients achieving sustained virologic response for hepatitis C virus.

Understanding the dynamics of serum Mac-2 binding protein glycosylation isomer (M2BPGi) remains pivotal for hepatitis C virus (HCV) patients' post-sustained virologic response (SVR12) through direct-acting antivirals (DAAs). We compared areas under receiver operating characteristic curves (AUROCs) of M2BPGi, FIB-4, and APRI and assess M2BPGi cutoff levels in predicting fibrosis stages of ≥F3 and F4 utilizing transient elastography in 638 patients. Variations in M2BPGi levels from pretreatment to SVR12 and their association with pretreatment alanine transaminase (ALT) levels and fibrosis stage were investigated. The AUROCs of M2BPGi were comparable to FIB-4 in predicting ≥F3 (0.914 vs 0.902, P=0.48) and F4 (0.947 vs 0.915, P=0.05) but were superior to APRI in predicting ≥F3 (0.914 vs 0.851, P=0.001) and F4 (0.947 vs 0.857, P<0.001). Using M2BPGi cutoff values of 2.83 and 3.98, fibrosis stages of ≥F3 and F4 were confirmed with a positive likelihood ratio ≥10. The median M2BPGi change was -0.55. Patients with ALT levels ≥5 times ULN or ≥F3 demonstrated more pronounced median decreases in M2BPGi level compared to those with ALT levels 2-5 times ULN and <2 times ULN (-0.97 vs -0.68 and -0.44; P<0.001) or with < F3 (-1.52 vs -0.44; P<0.001). Serum M2BPGi is a reliable marker for advanced hepatic fibrosis. Following viral clearance, there is a notable M2BPGi decrease, with the extent of reduction influenced by ALT levels and fibrosis stage.

Association of Serum M2BPGi Levels with Nutritional Status (Using CONUT score) in Hepatitis C Virus Related Compensated Liver Cirrhosis Patients

Abstract Background Protein-energy malnutrition (PEM), which is one of the most common complications seen in LC patients and associated with high morbidity and mortality. So, predicting the presence of PEM and providing appropriate nutritional support help improve the prognosis of those patients. Mac-2-binding protein glycosylation isomer (M2BPGi) was recently identified as a serum glycobiomarker for liver fibrosis. However, the relationship between M2BPGi and malnutrition in patients with chronic liver disease (CLD) is unclear. Aim of the Work The aim of this study is to evaluate the role of serum M2BPGi levels as a surrogate marker for malnutrition in HCV related cirrhotic patients, correlated with CONUT score as the nutritional status marker. Patients and Methods This is a Cross-sectional - Analytic study that included patients with chronic HCV infection and normal control group selected from patients attending to Hepatology Outpatient Clinics at Ain Shams University Hospital. This study was carried out from 30 patients (child A) attending to Hepatology Outpatient Clinics at Ain Shams University Hospital and 30 healthy individuals as a control. Results The M2BPGi levels increased with CONUT score. The correlation coefficient between M2BPGi and CONUT score was r = 0.315 (p = 0.05), indicating a positive weak correlation between M2BPGi and CONUT score. The cut-off for M2BPGi to predict CONUT low vs. moderate was 1.43 with a sensitivity 93.33% and specificity 100% when AUC =0.9 and CONUT moderate vs. severe was 1.7 with a sensitivity 91.67% and specificity 100% when AUC =0.9. Conclusion We found that there is correlation between M2BPGi and CONUT score and both can be useful as a marker for malnutrition in HCV related cirrhotic patients cut of point

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.

Proposal of a Novel Serological Algorithm Combining FIB-4 and Serum M2BPGi for Advanced Fibrosis in Nonalcoholic Fatty Liver Disease.

Noninvasive methods have become increasingly critical in the diagnosis of fibrosis in chronic liver diseases. Herein, we compared the diagnostic performance of serum Mac2 binding protein glycosylation isomer (M2BPGi) and other serological panels for fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) and proposed an improved two-step diagnostic algorithm for advanced fibrosis. We enrolled 231 patients diagnosed with NAFLD who underwent a liver biopsy. We subsequently evaluated the diagnostic performance of serological panels, including serum M2BPGi, a fibrosis index based on four factors (FIB-4), aspartate aminotransferase-to-platelet ratio index (APRI), and NAFLD fibrosis score (NFS), in predicting the stage of liver fibrosis. We then constructed a two-step algorithm to better differentiate advanced fibrosis. The areas under the receiver operating characteristic curves of serum M2BPGi, FIB-4, APRI, and NFS for advanced fibrosis (≥F3) were 0.823, 0.858, 0.779, and 0.827, respectively. To reduce the performance of unnecessary liver biopsy, we propose a two-step algorithm using FIB-4 as an initial diagnostic tool and serum M2BPGi (≥0.6) as an additional diagnostic method for patients classified as intermediate (23%). Using the proposed algorithm, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 0.812, 0.814, 0.814, 0.600, and 0.927, respectively. Serum M2BPGi is a simple and effective test for advanced fibrosis in patients with NAFLD. Application of the two-step algorithm based on FIB-4 and M2BPGi proposed here can improve diagnostic performance and reduce unnecessary tests, making diagnosis easily accessible, especially in primary medical centers.

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.

Biological variation and reference change values of serum Mac-2-binding protein glycosylation isomer (M2BPGi).

BackgroundLimited data are available with regard to biological variations of the Mac‐2–binding protein glycosylation isomer (M2BPGi), a liver fibrosis biomarker.MethodsLong‐term biological variation of M2BPGi was investigated using longitudinally measured M2BPGi test results from healthy Korean adult subjects. One‐way analysis of variance (ANOVA) tests were used to calculate the reference change value (RCV) of M2BPGi based on biological variation estimates. Furthermore, asymmetric RCV was calculated according to a recent publication of the European Federation of Clinical Chemistry and Laboratory Medicine Working Group on Biological Variation and Task Group for the Biological Variation Database (EFLM TG‐BVD).ResultsA total of 363 test results from 174 Korean subjects undergoing general health checkups were requested from 13 local clinics and hospitals during a 38‐month period. The within‐subjects biological variation (CVI), between‐subject biological variation (CVG), analytical variation (CVA), RCV, and individuality index (II) values for serum M2BPGi were 23.3%, 30.0%, 4.3%, 65.6%, and 0.78, respectively. Asymmetric RCV calculated using formulae by a recent EFLM TG‐BVD publication ranged from −41.9 to 72.0%. Desirable analytical performance specifications for M2BPGi derived from biological variation were as follows: imprecision 11.6%, bias 9.6%, and total allowable error 28.7%.ConclusionsRCV based on biological estimates may be helpful for evaluating and interpreting serial M2BPGi measurements by physicians and in clinical laboratories.

Role of Serum M2BPGi Levels in Predicting Persistence of Advanced Fibrosis in Chronic Hepatitis B Virus Infection.

Serum mac-2-binding protein glycosylation isomer (M2BPGi) is a novel marker for liver fibrosis assessment in patients with different liver diseases. For chronic hepatitis B infection (CHB), advanced fibrosis or cirrhosis is a risk factor for liver cancer and hepatic decompensation. We aimed to assess the role of serum M2BPGi in prediction of persistence of advanced fibrosis in CHB patients despite potent antiviral therapy. CHB patients with advanced fibrosis or cirrhosis who were put on nucleos(t)ide analogs for ≥ 3years with normal alanine aminotransferase and undetectable serum HBV DNA were prospectively recruited. Assessment of liver fibrosis with transient elastography (TE) and M2BPGi measurements were performed at baseline and repeated at 3years. Advanced fibrosis and cirrhosis were defined by liver stiffness (LS) ≥ 9.0kPa and ≥ 12.0kPa, respectively. A total of 143 patients (M:F = 101:42; median age 58.7years; 53.8% cirrhotic) were recruited and completed paired assessment. The median value of baseline LS and M2BPGi were 12.0 (IQR: 10.5-18.2) kPa and 0.99 cut-off-index (IQR: 0.75-1.74) (COI), respectively, with 96% concordance for diagnosing F3/F4. Ninety-six (67.1%) patients had persistent advanced fibrosis or cirrhosis at 3years despite continuation of long-term antiviral treatment. Upon multivariate analysis, baseline M2BPGi (OR 2.128, 95% CI 1.037-4.366) and presence of central obesity (OR 4.648, 95% CI 1.742-12.402) were significantly associated with persistent advanced fibrosis or cirrhosis at 3years. Baseline M2BPGi ≥ 1.265 COI has 50.6% sensitivity and 79.4% specificity for predicting persistent advanced fibrosis or cirrhosis at 3years (area under the receiver-operating characteristic curve: 0.695). The presence of central obesity in combination with baseline M2BPGi ≥ 1.265 COI was associated with 95.7% patients having persistent advanced fibrosis or cirrhosis at 3years. HCC development was observed in five patients during follow-up and was associated with bigger median increase in the level of serum M2BPGi compared to patients without HCC (46% vs 6.2%, P = 0.038). Persistent advanced fibrosis or cirrhosis was observed in two-thirds of CHB patients despite potent antiviral therapy. High serum M2BPGi and central obesity were associated with more than twofold and fourfold increase in risk of persistent advanced fibrosis or cirrhosis, respectively.

Baseline serum Mac-2 binding protein glycosylation isomer as a predictor of hepatocellular carcinoma in chronic hepatitis B patients: a systematic review and meta-analysis

A minimally invasive tool to promptly predict hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) is currently needed. In this study, we aimed via a meta-analysis to identify the serum Mac-2 binding protein glycosylation isomer (M2BPGi) as a novel glycoprotein-based liver fibrosis marker for predicting HCC in CHB patients. We conducted a systematic search on PubMed, Scopus, ProQuest, Wiley Online Library, and CINAHL Plus (via EBSCOhost). The articles were screened based on several eligibility criteria and were further assessed for study qualities using the Newcastle-Ottawa Scale. The outcomes were presented as standard mean difference (SMD), hazard ratio (HR), and predictive accuracy parameters of a baseline cutoff index (COI) for serum M2BPGi. Fourteen studies involving 5918 CHB patients were included in this systematic review and meta-analysis. Baseline COI serum M2BPGi was significantly higher in CHB patients who developed HCC than in those who did not (SMD 1.32, 95% confidence interval [CI] 0.91-1.72). A significant HCC risk prediction was also observed (multivariate HR 1.18, 95%CI 1.05-1.32). Baseline COI serum M2BPGi could predict HCC with a pooled sensitivity of 74% (95%CI 50-89%), specificity of 80% (95%CI 65-90%), and area under the summary receiver operating characteristic curve of 0.84 (95%CI 0.81-0.87). High baseline COI serum M2BPGi may predict the development of HCC in CHB patients with moderate-to-high accuracy.

Use of M2BPGi in HCC patients with TACE.

Serum Mac-2-binding protein glycosylation isomer (M2BPGi) has been studied as a marker for liver fibrosis or cirrhosis. This study explores the potential role of M2BPGi in predicting clinical outcomes of patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE). A total of 226 HCC patients undergoing TACE were enrolled. Serum M2BPGi was measured at baseline. Receiver operating characteristic curve analysis was used to determine the cut-off value (=2.82) of M2BPGi for prediction of patient outcomes. The prognostic performance of M2BPGi was compared with the hepatoma arterial embolization prognostic (HAP) score. The primary outcome was progression-free survival (PFS). Secondary outcomes included overall survival (OS), radiologic response, and recurrence after complete response (CR). Median PFS was 14.5months. Patients with low M2BPGi levels had significantly better OS and PFS than those with high M2BPGi levels. M2BPGi was an independent variable for PFS and OS. Patients were classified into three groups by combination of M2BPGi and the HAP score. The low-risk group had significantly better PFS and OS than the high-risk and intermediate-risk groups, whereas the differences between the high-risk and intermediate-risk groups were insignificant. The combination showed higher area under the receiver operating characteristic curve for 3-year PFS and OS than the HAP score alone. M2BPGi was a significant predictor of HCC recurrence after achieving CR. Serum M2BPGi level is a useful prognostic indicator of PFS and OS in TACE-treated HCC patients, as well as recurrent cases, which cannot be predicted with the HAP score. The combination of M2BPGi and the HAP score enhances the detection of TACE-preferred patients.