Mac-2 binding protein glycan isomer (M2BPGi) is a new serum biomarker for assessing liver fibrosis: more than a biomarker of liver fibrosis

Shirabe, Ken; Bekki, Yuki; Gantumur, Dolgormaa; Araki, Kenichiro; Ishii, Norihiro; Kuno, Atsushi; Narimatsu, Hisashi; Mizokami, Masashi

doi:10.1007/s00535-017-1425-z

Cited by 148 publications

(164 citation statements)

References 71 publications

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“…In addition to the liver stiffness value measured by FibroScan and AST‐to‐platelet ratio, several studies focused on other noninvasive methods for evaluating liver fibrosis in the CHB population, such as the fibrosis index based on 4 factors (age, platelet count, ALT, and AST) and the Forn index (a formula based on the platelet count, γ‐glutamyl transferase, age, and cholesterol). Both of them can detect liver fibrosis successfully .…”

Section: Discussionmentioning

confidence: 99%

Dynamic Changes of the Aspartate Aminotransferase‐to‐Platelet Ratio and Transient Elastography in Predicting a Histologic Response in Patients With Chronic Hepatitis B After Entecavir Treatment

Sun

et al. 2018

J of Ultrasound Medicine

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Objectives To evaluate the dynamic changes of the aspartate aminotransferase (AST)‐to‐platelet ratio and transient elastography (FibroScan; Echosens, Paris, France) in predicting a histologic response in patients with chronic hepatitis B (CHB) after entecavir treatment. Methods A total of 148 patients with CHB were enrolled. Patient information was collected. All patients received liver biopsy and FibroScan before and after 96 weeks of entecavir treatment. Results Baseline liver biopsy results showed that there were 7 patients without liver fibrosis (fibrosis stage F0; 4.7%), 51 patients with mild liver fibrosis (F1; 34.5%), and 90 patients with advanced liver fibrosis (>F1; 60.9%). The liver stiffness value and AST‐to‐platelet ratio increased significantly as the METAVIR score of the patients increased from F0 to F4 (P < .001). After antiviral therapy for 96 weeks, the average liver stiffness value measured by FibroScan and the AST‐to‐platelet ratio showed a significant decrease. When we use a decreased liver stiffness value to predict a histologic response, the area under the receiver operating characteristic curve was 0.70 (95% confidence interval, 0.61–0.79; P < .001), and the sensitivity and specificity were 74.3% and 68.8%, respectively. The decrease of the AST‐to‐platelet ratio also could predict the histologic response of patients with CHB; the area under the receiver operating characteristic curve was 0.77 (95% confidence interval, 0.69–0.86; P < .001) with sensitivity of 76.2% and specificity of 70.2%. A multivariate analysis indicated that a high hepatitis B virus DNA viral load (odds ratio, 1.44; P = .04) and high METAVIR score (odds ratio, 1.38; P = .02) were independent risk factors for the histologic response. Conclusions Both the AST‐to‐platelet ratio and FibroScan value can effectively predict a histologic response in patients with CHB during entecavir treatment. Therefore, they can be used to monitor these patients during antiviral treatment to avoid multiple liver biopsies.

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Section: Discussionmentioning

confidence: 99%

Dynamic Changes of the Aspartate Aminotransferase‐to‐Platelet Ratio and Transient Elastography in Predicting a Histologic Response in Patients With Chronic Hepatitis B After Entecavir Treatment

Sun

et al. 2018

J of Ultrasound Medicine

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“…M2BP is a glycoprotein produced by hepatic stellate cells and is present in small amount in many tissues in human body, including the extracellular matrix in the liver. It is extensively glycosylated, that is, becomes M2BPGi, and interacts with galectin‐3 (Mac‐2) and other extracellular matrix molecules and functions as a messenger between hepatic stellate cells and Kupffer cells for promotion of fibrogenesis . Therefore, it has been studied as a surrogate marker of liver fibrosis in various liver diseases including viral hepatitis .…”

Section: Introductionmentioning

confidence: 99%

“…It is extensively glycosylated, that is, becomes M2BPGi, and interacts with galectin-3 (Mac-2) and other extracellular matrix molecules and functions as a messenger between hepatic stellate cells and Kupffer cells for promotion of fibrogenesis. 16 Therefore, it has been studied as a surrogate marker of liver fibrosis in various liver diseases including viral hepatitis. [17][18][19][20][21] A recent paper reported that a high serum M2BPGi at 48 weeks of antiviral therapy predicted HCC development in 234 CHB patients during 51 months of follow-up.…”

Section: Introductionmentioning

confidence: 99%

Serum Mac‐2‐binding protein glycosylation isomer and risk of hepatocellular carcinoma in entecavir‐treated chronic hepatitis B patients

Mak

et al. 2019

J of Gastro and Hepatol

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Background and Aim Hepatocellular carcinoma (HCC) can still develop in chronic hepatitis B (CHB) patients receiving antiviral treatment. Serum Mac‐2‐binding protein glycosylation isomer (M2BPGi) is a novel marker for liver fibrosis. We investigated its role on incidence of HCC in entecavir (ETV)‐treated CHB patients. Methods We identified HCC cases diagnosed at ≥ 1 year of ETV treatment. CHB patients without HCC (matched for age, gender, baseline hepatitis B virus‐DNA, and duration of ETV treatment) were identified in approximately 1:2 ratio (HCC: non‐HCC) for comparison. Serum samples were retrieved at baseline (initiation of ETV), 3, and 5 years of ETV for serum M2BPGi measurement (expressed in cut‐off index [COI]). Results One hundred HCC cases were matched with 185 CHB patients without HCC (median age 56.7 years, 78.9% male, baseline hepatitis B virus‐DNA 5.6 logIU/mL, and median follow‐up 7.1 years). Median time from ETV initiation to incident HCC was 3.9 years. Serum M2BPGi levels were significantly higher in HCC cases compared with controls at baseline and year 3 (1.25 vs 0.98 [P = 0.004], 0.89 vs 0.74 [P = 0.018] COI, respectively). Multivariate analysis showed that baseline M2BPGi was the only independent factor associated with incident HCC (odds ratio 1.241, 95% confidence interval 1.039–1.482, P = 0.017). Using a cut‐off value of 1.15 COI, the sensitivity, specificity, positive predictive value, and negative predictive value of baseline serum M2BPGi in cirrhotic patients to predict incident HCC were 90%, 53.8%, 69.6%, and 82.1%, respectively. Conclusions Baseline and 3‐year serum M2BPGi may be useful to identify high risk patients on antiviral treatment for subsequent HCC development.

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“…M2BP is widely expressed in various human tissues, but a liver‐specific glycosylation isomer (M2BPGi) can be determined and quantified using the Wisteria floribunda agglutinin immunoassay that is already commercially available in Japan . In the recent years, M2BPGi has emerged as a novel biomarker that correlates well with hepatic fibrosis in patients with chronic liver diseases . Recent literature also suggests that M2BPGi may correlate with hepatocellular carcinoma (HCC) development in patients with chronic viral hepatitis, but most have been conducted in patients with chronic hepatitis C (CHC) or untreated chronic hepatitis B (CHB) without serial measurements …”

Section: Introductionmentioning

confidence: 99%

“…2 In the recent years, M2BPGi has emerged as a novel biomarker that correlates well with hepatic fibrosis in patients with chronic liver diseases. 3 Recent literature also suggests that M2BPGi may correlate with hepatocellular carcinoma (HCC) development in patients with chronic viral hepatitis, but most have been conducted in patients with chronic hepatitis C (CHC) or untreated chronic hepatitis B (CHB) without serial measurements. [4][5][6][7][8] Indeed, the serum concentration of M2BPGi is not static and may change in a relatively short period of time, especially in the setting of anti-viral therapies.…”

Section: Introductionmentioning

confidence: 99%

Serum M2BPGi level and risk of hepatocellular carcinoma after oral anti‐viral therapy in patients with chronic hepatitis B

Hsu

Jun

Huang

et al. 2018

Aliment Pharmacol Ther

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Summary Background Mac‐2 binding protein glycosylation isomer (M2BPGi) is an emerging biomarker for risk prediction of liver disease, but data remain sparse for patients with chronic hepatitis B (CHB) who are treated with nucleos(t)ide analogues (NA). Aim To clarify serial changes in M2BPGi and its association with subsequent hepatocellular carcinoma (HCC) development in NA‐treated CHB patients. Methods We enrolled 384 previously untreated CHB patients who received NAs. Among them, 195 had baseline cirrhosis (n = 142:48:5 for Child A:B:C). Sera were collected at NA initiation, and after 1 and 2 years. Serum M2BPGi levels were measured and expressed as cut‐off index (COI) at different time points. The association between M2BPGi and HCC was evaluated by the Cox proportional hazard model. Results The median M2BPGi levels significantly decreased from 1.68 COI at baseline, to 1.0 at year 1, and 0.88 at year 2. During median follow‐up of 72.7 months, HCC occurred in 37 patients, 36 of whom had cirrhosis. In patients with cirrhosis, baseline M2BPGi level was associated with HCC risk (adjusted hazard ratio, 1.07 per COI; 95% CI, 1.01‐1.14) on the multivariable Cox analysis, whereas levels at year 1 or 2 were not independently predictive. A risk score for HCC was developed using baseline M2BPGi, age and body mass index with c statistics of 0.77, 0.79 and 0.87 at 3, 5 and 10 years, respectively. Conclusions Serum M2BPGi level significantly decreases after NA treatment in CHB patients. Baseline level can be factored into the risk prediction of HCC in NA‐treated patients with cirrhosis.

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Mac-2 binding protein glycan isomer (M2BPGi) is a new serum biomarker for assessing liver fibrosis: more than a biomarker of liver fibrosis

Cited by 148 publications

References 71 publications

Dynamic Changes of the Aspartate Aminotransferase‐to‐Platelet Ratio and Transient Elastography in Predicting a Histologic Response in Patients With Chronic Hepatitis B After Entecavir Treatment

Dynamic Changes of the Aspartate Aminotransferase‐to‐Platelet Ratio and Transient Elastography in Predicting a Histologic Response in Patients With Chronic Hepatitis B After Entecavir Treatment

Serum Mac‐2‐binding protein glycosylation isomer and risk of hepatocellular carcinoma in entecavir‐treated chronic hepatitis B patients

Serum M2BPGi level and risk of hepatocellular carcinoma after oral anti‐viral therapy in patients with chronic hepatitis B

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