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* Background The level of liver fibrosis is the basis for the treatment of chronic hepatitis B (CHB), and it is necessary to adapt non-invasive liver fibrosis modalities. We aimed to investigate the use of M2BPGi as a single or combined diagnostic modality for liver fibrosis in CHB patients through a stepwise diagnostic analysis. Methods Cross-sectional data were taken from patients between October 2021 and August 2022. Demographic data, blood profile, liver function, and liver stiffness were measured in CHB patients over 18 years old, willing to take part in the research, and had complete data. APRI, FIB-4, and AAR were calculated using the well-known formulas. Serum M2BPGi-levels were converted into a cut-off index (COI). The patients were divided into low-risk (LR) and high-risk fibrosis (HR) groups. A cut-off for each predictor variable to differentiate between the LR and HR groups was determined. The obtained cut-off was assessed for its association with the grouping of liver elastography results. Models to diagnose the liver stiffness measurement (LSM) ≥8 kPa were created and compared through multivariate and ROC analyses. Results The number of patients that met the inclusion and exclusion criteria was 143 (HR = 65, LR = 78). The cut-off for diagnosing LSM ≥8kPa was 0.311, 0.742, 0.635, and 1.434 for APRI, FIB-4, AAR, and M2BPGi, respectively. This cut-off was significantly associated with the results of the HR and LR groupings. A multivariate analysis found that FIB4, AAR, and M2BPGi added significantly to the model. Statistically, the most optimal use of M2BPGi was combined with FIB-4, with an AUC of 0.835. Conclusions The optimal cut-off of M2BPGi for diagnosing high-risk liver fibrosis in this study was 1.434. M2BPGi should be used with FIB-4 as a diagnostic tool for diagnosing liver fibrosis, especially in the absence of a liver biopsy or elastography.

Abstract* Background The level of liver fibrosis is the basis for the treatment of chronic hepatitis B (CHB), and it is necessary to adapt non-invasive liver fibrosis modalities. We aimed to investigate the use of M2BPGi as a single or combined diagnostic modality for liver fibrosis in CHB patients through a stepwise diagnostic analysis. Methods Cross-sectional data were taken from patients between October 2021 and August 2022. Demographic data, blood profile, liver function, and liver stiffness were measured in CHB patients over 18 years old, willing to take part in the research, and had complete data. APRI, FIB-4, and AAR were calculated using the well-known formulas. Serum M2BPGi-levels were converted into a cut-off index (COI). The patients were divided into low-risk (LR) and high-risk fibrosis (HR) groups. A cut-off for each predictor variable to differentiate between the LR and HR groups was determined. The obtained cut-off was assessed for its association with the grouping of liver elastography results. Models to diagnose the liver stiffness measurement (LSM) ≥8 kPa were created and compared through multivariate and ROC analyses. Results The number of patients that met the inclusion and exclusion criteria was 143 (HR = 65, LR = 78). The cut-off for diagnosing LSM ≥8kPa was 0.311, 0.742, 0.635, and 1.434 for APRI, FIB-4, AAR, and M2BPGi, respectively. This cut-off was significantly associated with the results of the HR and LR groupings. A multivariate analysis found that FIB4, AAR, and M2BPGi added significantly to the model. Statistically, the most optimal use of M2BPGi was combined with FIB-4, with an AUC of 0.835. Conclusions The optimal cut-off of M2BPGi for diagnosing high-risk liver fibrosis in this study was 1.434. M2BPGi should be used with FIB-4 as a diagnostic tool for diagnosing liver fibrosis, especially in the absence of a liver biopsy or elastography.

* Background The level of liver fibrosis is the basis for the treatment of chronic hepatitis B (CHB), and it is necessary to adapt non-invasive liver fibrosis modalities. We aimed to investigate the use of M2BPGi as a single or combined diagnostic modality for liver fibrosis in CHB patients through a stepwise diagnostic analysis. Methods Cross-sectional data were taken from patients between October 2021 and August 2022. Demographic data, blood profile, liver function, and liver stiffness were measured in CHB patients over 18 years old, willing to take part in the research, and had complete data. APRI, FIB-4, and AAR were calculated using the well-known formulas. Serum M2BPGi-levels were converted into a cut-off index (COI). The patients were divided into low-risk (LR) and high-risk fibrosis (HR) groups. A cut-off for each predictor variable to differentiate between the LR and HR groups was determined. The obtained cut-off was assessed for its association with the grouping of liver elastography results. Models to diagnose the liver stiffness measurement (LSM) ≥8 kPa were created and compared through multivariate and ROC analyses. Results The number of patients that met the inclusion and exclusion criteria was 143 (HR = 65, LR = 78). The cut-off for diagnosing LSM ≥8kPa was 0.311, 0.742, 0.635, and 1.434 for APRI, FIB-4, AAR, and M2BPGi, respectively. This cut-off was significantly associated with the results of the HR and LR groupings. A multivariate analysis found that FIB4, AAR, and M2BPGi added significantly to the model. Statistically, the most optimal use of M2BPGi was combined with FIB-4, with an AUC of 0.835. Conclusions The optimal cut-off of M2BPGi for diagnosing high-risk liver fibrosis in this study was 1.434. M2BPGi should be used with FIB-4 as a diagnostic tool for diagnosing liver fibrosis, especially in the absence of a liver biopsy or elastography.

Background: The accurate evaluation of liver fibrosis is crucial for the treatment and follow up of chronic hepatitis B (CHB) patients. Aim: We examined the efficiency of serum Mac-2 Binding Protein Glycosylation isomer (M2BPGi) in diagnosing liver fibrosis stages in CHB patients. Methods: A cross-sectional study was conducted on 177 adult CHB patients visiting the University Medical Center Ho Chi Minh City, Vietnam between October 2019 and December 2021. M2BPGi, ARFI, APRI, and FIB-4 were tested against FibroScan® for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The optimal M2BPGi cut-off values were identified based on the area under the receiver operating characteristic (AUROC) curve. Results: There was a strong agreement between M2BPGi and FibroScan® (r = 0.77, P < 0.001). The optimal M2BPGi cut-off index (C.O.I) for detecting significant fibrosis (F ≥ 2) was 0.79 with an AUROC of 0.77, 67.3% sensitivity, 70% specificity, 60.6% NPV, and 75.3% PPV. Compared with APRI (61%) and FIB-4 (47%), M2BPGi had the greatest sensitivity for diagnosing F ≥ 2. M2BPGi combined with APRI yielded highest diagnosis performance for F ≥ 2 with an AUROC of 0.87. The optimal cut-off index of M2BPGi for diagnosing cirrhosis (F4) was 1.3 with an AUROC of 0.91, 88% sensitivity, 87.4% specificity, 97% NPV, and 61% PPV. The AUROC of M2BPGi for diagnosing F4 was comparable to that of ARFI (0.93). Conclusions: With cut-off values of 0.79 C.O.I and 1.3 C.O.I, M2BPGi could be an effective method for diagnosing significant fibrosis and cirrhosis in CHB patients, respectively. [ABSTRACT FROM AUTHOR]

Aim: The enhanced liver fibrosis (ELF) test is a noninvasive method for diagnosing hepatic fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). This multicenter cohort study aimed to evaluate the accuracy of the ELF test and compare it with other noninvasive tests in Japan. Methods: We analyzed 371 Japanese patients with biopsy‐proven NAFLD. We constructed area under the receiver operator characteristic curves (AUROC) to determine the diagnostic accuracies of the ELF test, the Mac‐2‐binding protein glycosylation isomer (M2BPGi), the Fibrosis‐4 (FIB‐4) index, and combinations of these indices. Results: In patients with F0/F1/F2/F3/F4 fibrosis, the median values of the ELF test were 8.98/9.56/10.39/10.92/11.41, respectively. The AUROCs of the ELF test for patients with F0 versus F1–4, F0–1 versus F2–4, F0–2 versus F3–4, and F0–3 versus F4 fibrosis were 0.825/0.817/0.802/0.812, respectively. The AUROCs of the ELF test were greater than those of the FIB‐4 index and M2BPGi at each fibrosis stage. Respective low and high cut‐off values yielded sensitivities and specificities for predicting advanced fibrosis (≥F3) of 91.1% and 50.8%, and 38.5% and 92.8%, respectively. For F3 or F4 fibrosis, the combined values from the ELF test and FIB‐4 index showed a sensitivity of 98.5%, and the combined values from the ELF test and M2BPGi assay showed a specificity of 97.5%. Conclusions: In Japan, the ELF test predicts NAFLD‐related fibrosis from its early stages. The diagnostic ability of the ELF test was not inferior to that of other indices, and the combined values of ELF plus other indices were more accurate. [ABSTRACT FROM AUTHOR]

Aim: To assess M2BPGi serum performance compared to liver biopsy in diagnosisng liver fibrosis Method: Literature search using Pubmed®, Ebsco®, ProQuest®, Scopus®, Clinical Key databases, and the Cochrane Library® yield four relevant and full-text articles. The four articles were critically appraised for its validity, importance, and applicability. Results: Sensitivity and specificity in all four studies showed that M2BPGi serum was inadequate to ruling in and ruling out the diagnosis of liver fibrosis in chronic hepatitis B patients. The difference in M2BPGi cut-off value to determine the stage of fibrosis in each study makes this value cannot be used as an accurate standard to determine the advanced stage (F≥3) of liver fibrosis. On the other hand, M2BPGi serum combined with other tests are known to improve the diagnostic accuracy. Conclusion: MBP2Gi serum cannot be used as a diagnostic modality for detecting liver fibrosis in chronic hepatitis B patients.

Aim: Fibrosis regression has been observed in patients with chronic hepatitis C virus (HCV) infection treated with direct‐acting antivirals. This study was aimed at evaluating dynamic changes of serum Mac‐2‐binding protein glycosylation isomer (M2BPGi) in patients with HCV genotype 1 receiving elbasvir/grazoprevir. Methods: M2BPGi were serially measured at baseline, during and after therapy. Its diagnostic performance at baseline and sustained virological response at 24 weeks after treatment (SVR24) were compared with transient elastography (TE) and the aspartate aminotransferase/platelet ratio index (APRI) using magnetic resonance elastography (MRE) as a reference. Results: Overall, 60 HCV mono‐infected and 36 HCV/HIV co‐infected patients were included with SVR24 rates of 93.3% and 97.2%, respectively. At baseline, TE, M2BPGi and APRI were correlated with MRE (r = 0.788, r = 0.703 and r = 0.564, respectively, p < 0.001). The area under the receiver operator characteristics curves for TE, M2BPGi and APRI in differentiating significant fibrosis were 0.88 (95% confidence interval; 0.81–0.95, p < 0.001), 0.86 (0.79–0.94, p < 0.001) and 0.74 (0.64–0.83, p < 0.001), respectively. The corresponding figures for cirrhosis were 0.95 (0.90–1.00, p < 0.001), 0.96 (0.92–1.00, p < 0.001) and 0.88 (0.79–0.97, p < 0.001), respectively. Compared with baseline, all fibrosis markers significantly declined after achieving SVR24. The correlations of TE, M2BPGi and APRI with MRE at time of SVR24 were r = 0.587 (p < 0.001), r = 0.457 (p < 0.001) and r = 0.293 (p = 0.004), respectively. In multivariate analysis, high baseline alanine aminotransferase level, HCV mono‐infection and advanced fibrosis were factors associated with M2BPGi reduction. Conclusions: HCV eradication is associated with liver fibrosis improvement. M2BPGi has a better performance than APRI in monitoring liver fibrosis in patients treated with direct‐acting antivirals. This marker is applicable in resource‐limited settings where imaging‐based modalities are not widely accessible. [ABSTRACT FROM AUTHOR]

Background To investigate serum Mac-2-binding protein glycosylation isomer (M2BPGi) levels in predicting hepatocellular carcinoma (HCC) and mortality at virological remission (VR, HBV DNA <20 IU/mL) following antiviral therapy in chronic hepatitis B (CHB) patients with cirrhosis. Methods This retrospective cohort study included patients with CHB-related Child-Pugh A cirrhosis undergoing long-term antiviral therapy. Serum M2BPGi levels were quantified and multivariable Cox proportional hazards regression models were used to identify risk predictors for HCC and death. Results A total of 126 and 145 patients were included in the derivation and validation cohorts, respectively. The mean age was 56, and the mean M2BPGi level was 1.86 cut-off index (COI) in the derivation cohort. After adjustment for confounders, a higher M2BPGi level at VR significantly predicted HCC (hazard ratio [HR]: 1.58, 95% confidence interval [CI]: 1.19-2.10, P=0.002) and death (HR: 2.17, 95% CI: 1.02-4.62, P=0.044). The M2BPGi ≥3 COI significantly increased the risk of HCC and death in the derivation and validation cohorts. Serial M2BPGi levels declined significantly (P=0.0001) in non-HCC patients only, and remained significantly lower than those who developed HCC afterwards (P=0.039). Conclusions Serum M2BPGi levels at antiviral therapy-induced VR predict HCC development and death in patients with CHB-related Child-Pugh A cirrhosis. [ABSTRACT FROM AUTHOR]

Wisteria floribunda agglutinin‐positive Mac‐2‐binding protein (M2BP) has been identified as a predictor for the response of interferon α (IFN‐α) in patients with viral hepatitis. However, whether serum glycosylation isomer of M2BP (M2BPGi) was associated with the regression of liver fibrosis in patients with chronic hepatitis B (CHB) during IFN‐α add‐on therapy is still unknown. CHB patients were treated with entecavir for 26 weeks followed by entecavir plus pegylated IFN‐α for 52 weeks. Liver biopsies were taken at baseline and treatment week 78. The regression of fibrosis was identified according to Ishak standard or Ishak plus Progressive‐Indeterminate‐Regressive (P‐I‐R) standard. Serum M2BPGi and liver function tests were measured at baseline and every 26 weeks of treatment. A total of 72 CHB patients were included in the present study. Serum M2BPGi was correlated with fibrosis and necroinflammation both at baseline and week 78. If Ishak standard was used as the reference, only the percent change of M2BPGi at week 52 from week 26 (Δ%M2BPGi26w‐52W) was independently associated with fibrosis regression at treatment week 78, the area under the ROC curve (AUROC) of Δ%M2BPGi26w‐52W for predicting fibrosis regression was 0.705. As for Ishak plus P‐I‐R standard, the AUROC of the predictive model for fibrosis regression (0.896*M2BPGi52W + 0.363*necroinflammation score0w + 2.051*Ishak score0w – 4.489) was 0.888. These data indicated that dynamic changes of serum M2BPGi were associated with fibrosis regression in CHB patients on IFN‐α add‐on therapy. Highlight: Serum M2BPGi was correlated with fibrosis and necroinflammation.Dynamic changes of serum M2BPGi were associated with fibrosis regression in CHB patients on IFN α add‐on therapy. [ABSTRACT FROM AUTHOR]

Background: Our aims in this study were to evaluate the performance of the Mac-2 binding protein glycosylation isomer (M2BPGi), a liver fibrosis marker, using Sysmex HISCL following user verification guidelines before clinical use. We also evaluated the correlation between M2BPGi and hemoglobin A1c (HbA1c) because HbA1c is known as another biomarker associated with glycosylation. Methods: The analytical performance of M2BPGi was verified following user verification guidelines by the Clinical and Laboratory Standards Institute. Results: A qualitative, precision experiment for analyte concentrations near the cutoff was verified using quality control materials. The manufacturer's precision claims for the quantitative cutoff index were verified, with coefficients of variation in the range of 1.83 - 4.12%. HbA1c did not significantly contribute to M2BPGi in a multivariate analysis with an age factor. Conclusions: The analytical performance of M2BPGi in our results verify the manufacturer's claims. Clinical information and other findings, including HbA1c, are needed for clinical applications. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Liver biopsies have been partially replaced by noninvasive methods for assessing liver fibrosis. We explored the usefulness of four novel biomarkers, enhanced liver fibrosis (ELF), glycosylation isomer of Mac-2 binding protein (M2BPGi), galectin-3, and soluble suppression of tumorigenicity 2 (sST2), in association with liver fibrosis. Methods: ELF, M2BPGi, galectin-3, and sST2 were assayed in 173 patients with chronic liver diseases. The results were analyzed according to fibrosis grade (F0/1, F2, and F3/4) by transient elastography (TE). Results: ELF, M2BPGi, galectin-3, and sST2 values differed significantly according to TE grade; ELF and M2BPGi values were higher in F2 and F3/4 than in F0/1 (P≤0.001, all), sST2 values were higher in F3/4 than in F0/1 and F2 (P<0.05), and galectin-3 values were higher in F3/4 than in F0/1 (P=0.0036). ELF and M2BPGi showed good TE fibrosis detection performance (area under the curves [AUC], 0.841 and 0.833 for ≥F2; and 0.837 and 0.808 for ≥F3). The sensitivity and specificity for predicting TE grade F≥2 were 84.1% and 76.7% for ELF and 63.6% and 91.5% for M2BPGi. Conclusions: This is the first study to compare the liver fibrosis assessment of four novel biomarkers: ELF, M2BPGi, galectin-3, and sST2. The biomarkers varied significantly according to TE grade, and each biomarker showed a different trend. ELF and M2BPGi seem to have comparable good performance for detecting liver fibrosis. [ABSTRACT FROM AUTHOR]

Background: Wisteria floribunda agglutinin‐positive Mac‐2 binding protein (WFA+‐M2BP) is a novel serum marker of hepatic fibrosis in adults with chronic hepatitis C. However, it remains unclear whether serum WFA+‐M2BP levels are associated with the progression of liver histology in primary sclerosing cholangitis (PSC). Methods: Twenty‐eight children and adolescents with pediatric‐onset PSC (male : female patient ratio, 20:8; median age at diagnosis, 9 years) were enrolled in this study. The relation between serum WFA+‐M2BP levels and clinical characteristics was retrospectively evaluated. Moreover, receiver operating characteristic (ROC) analysis was used to determine whether serum WFA+‐M2BP levels could be a reliable marker to identify PSC patients with advanced liver histology. Results: According to the Ludwig classification of liver histological stage, 28 patients were classified into the four stages. The WFA+‐M2BP level, aspartate aminotransferase (AST) to platelet ratio index (APRI), and hyaluronic acid correlated significantly with liver histological stage. Moreover, WFA+‐M2BP showed a significant positive correlation (P < 0.05) with autoimmune hepatitis overlap, AST, alanine aminotransferase (ALT), γ‐glutamyltransferase, total bilirubin, immunoglobulin G, APRI, and hyaluronic acid. A ROC analysis was undertaken to distinguish the patients with advanced stage disease (stage 3–4) from those with early stage disease (stage 0–2). It showed that WFA+‐M2BP yielded the highest area under the ROC curve value (0.898) among four surrogate makers (APRI, 0.850; Fibrosis‐4 index, 0.806; and AST/ALT ratio, 0.802). Moreover, WFA+‐M2BP yielded the highest sensitivity, specificity, positive predictive value, and negative predictive value among the four markers. Conclusions: Serum WFA+‐M2BP levels are useful to identify patients with advanced liver histology in pediatric PSC. [ABSTRACT FROM AUTHOR]

Background and aim: Mac-2-binding protein glycosylation isomer (M2BPGi) is a novel serum diagnostic marker for liver fibrosis in various liver diseases. We aimed to evaluate its role in assessment of liver fibrosis in chronic hepatitis B infection (CHB) with reference to liver stiffness measurement (LSM) by transient elastography (Fibroscan). Design and Methods: A case control study. 50 CHB patients with LSM by transient elastography technology and retrievable serum samples and 20 normal volunteers as a control group were recruited. Results: 50 CHB patients (M: F = 30:20; mean age 43years 6 10.58) and 20 normal control volunteers (M: F= 12:8; mean age 37years 614.5) were recruited. The mean M2BPGi values for control group, F0-F1, F2, F3 and F4 progressively increased with more advanced stages of liver fibrosis: 0.282, 0.719, 1.322, 1.65 and 1.904 COI, respectively (p <0.001). M2BPGi levels correlated well with liver stiffness (r =0.911) and moderately with FIB-4 (r =0.682), and with APRI (r =0.536) (all p <0.001). Using cut-off values of 0.455, 1.02, 1.16, 1.66 and 1.71COI for control, F0-F1, F2, F3 and F4 groups, respectively, the AUROCs were 0.996, 0.996, 0.691, 0.794 and 1.00 for control, F0-F1, F2, F3 and F4 groups, respectively. There was a statistically significant but with weak positive correlation between M2BPGi serum level and INR (r = 0.333, p =0.018). And there was a statistically significant but with weak negative correlation between M2BPGi serum level and platelet count (r =-0.41, p =0.003) and HBV DNA (r =-0.373, p =0.008). There was a statistically significance between M2BPGi serum level and the history of varices (p =0.023) Conclusions: WFAþ-M2BP is an accurate serum indicator for assessing different stages of liver fibrosis. WFAþ-M2BP provides a simple and reliable alternative or complementary method to liver biopsy and FibroScan. [ABSTRACT FROM AUTHOR]

Background: To investigate serum Mac-2-binding protein glycosylation isomer (M2BPGi) levels in predicting hepatocellular carcinoma (HCC) and mortality at virological remission (VR, HBV DNA <20 IU/mL) following antiviral therapy in chronic hepatitis B (CHB) patients with cirrhosis.Methods: This retrospective cohort study included patients with CHB-related Child-Pugh A cirrhosis undergoing long-term antiviral therapy. Serum M2BPGi levels were quantified and multivariable Cox proportional hazards regression models were used to identify risk predictors for HCC and death.Results: A total of 126 and 145 patients were included in the derivation and validation cohorts, respectively. The mean age was 56, and the mean M2BPGi level was 1.86 cut-off index (COI) in the derivation cohort. After adjustment for confounders, a higher M2BPGi level at VR significantly predicted HCC (hazard ratio [HR]: 1.58, 95% confidence interval [CI]: 1.19-2.10, P=0.002) and death (HR: 2.17, 95% CI: 1.02-4.62, P=0.044). The M2BPGi ≥3 COI significantly increased the risk of HCC and death in the derivation and validation cohorts. Serial M2BPGi levels declined significantly (P=0.0001) in non-HCC patients only, and remained significantly lower than those who developed HCC afterwards (P=0.039).Conclusions: Serum M2BPGi levels at antiviral therapy-induced VR predict HCC development and death in patients with CHB-related Child-Pugh A cirrhosis. [ABSTRACT FROM AUTHOR]