Serum Levels of M2BPGi as Short-Term Predictors of Hepatocellular Carcinoma in Untreated Chronic Hepatitis B Patients

Liu, Jessica; Hu, Hui Han; Lee, Hsuan-Shu; Korenaga, Masaaki; Jen, C.-L.; Batrla-Utermann, Richard; Lu, Sheng; Wang, Li Yu; Mizokami, Masashi; Chen, Chien Jen; Yang, Hwai I.

doi:10.1038/s41598-017-14747-5

Cited by 28 publications

(25 citation statements)

References 38 publications

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“…It is possible that alternative lectins could improve the test’s performance in non‐Japanese HCV populations. For HBV, M2BPGi has been successfully used in Korean and Chinese populations in addition to Japanese populations, demonstrating that the test is robust to some changes in patient population …”

Section: Discussionmentioning

confidence: 99%

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Mac‐2 Binding Protein Glycosylation Isomer as a Hepatocellular Carcinoma Marker in Patients With Chronic Hepatitis B or C Infection

Jun¹,

Hsu

Ogawa³

et al. 2019

Hepatol Commun

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Mac‐2 binding protein glycosylation isomer (M2BPGi) is a novel glycoprotein biomarker that correlates with liver fibrosis. It has been investigated in East Asian populations as a hepatocellular carcinoma (HCC) biomarker. We assessed M2BPGi as an HCC biomarker in an ethnically diverse cohort of patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. We enrolled 947 treatment‐naive patients mono‐infected with HBV or HCV without HCC at baseline. Biomarker levels were measured from baseline sera and correlated with longitudinal clinical data. The primary outcome was HCC occurrence during long‐term follow‐up. Median M2BPGi was significantly higher among patients with cirrhosis (2.67 versus 0.80; P < 0.001) and patients who developed HCC (3.22 versus 1.16; P < 0.001). The area under the receiver operating characteristic (AUROC) for M2BPGi and alpha‐fetoprotein (AFP) was similar overall (0.77 versus 0.72; P = 0.15), but M2BPGi outperformed AFP among patients with HBV (0.84 versus 0.75; P = 0.02). M2BPGi performed poorly among patients with HCV (AUROC, 0.51). M2BPGi was an independent predictor of HCC among patients with HBV but not among patients with HCV. M2BPGi performed better in patient subgroups with a lower prevalence of cirrhosis. Conclusion: In our HBV cohort, M2BPGi was more effective than AFP in predicting HCC and was an independent predictor of HCC. However, M2BPGi had limited predictive value in our HCV cohort, likely due to a high cirrhosis burden in this cohort. Further studies are needed to evaluate M2BPGi as an HCC biomarker in broader patient populations with more diverse disease etiology, non‐Asian ethnicity, and more advanced fibrosis.

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Section: Discussionmentioning

confidence: 99%

“…In addition to HCV, the Mac‐2 binding protein glycosylation isomer (M2BPGi) has been studied as a marker for fibrosis in chronic hepatitis B virus (HBV) infection, nonalcoholic fatty liver disease (NAFLD), and primary biliary cirrhosis, among others . It has also been evaluated as a biomarker for HCC in HBV, HCV, and NAFLD, with favorable results …”

mentioning

confidence: 99%

Mac‐2 Binding Protein Glycosylation Isomer as a Hepatocellular Carcinoma Marker in Patients With Chronic Hepatitis B or C Infection

Jun¹,

Hsu

Ogawa³

et al. 2019

Hepatol Commun

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“…Besides its association with fibrosis, M2BPGi has also been studied as a marker of future HCC development in untreated CHB patients . Data on M2BPGi as a predictor for HCC for NA‐treated patients are much more limited by small sample size, lack of stratified analysis by cirrhosis which is a major confounder, and insufficient account for the time‐dependent nature of the association of M2BPGi levels and HCC development.…”

Section: Discussionmentioning

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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“…In patients without cirrhosis (n = 1,087), M2BPGi levels ≥1.8 were associated with a higher risk of HCC development (p < 0.001 by log-rank test), whereas M2BPGi levels ≥1.8 tended to be associated with a higher risk of HCC development in patients with cirrhosis (n = 236) (p = 0.073 by log-rank test) [83]. In another report, Liu et al described that M2BPGi was a strong and independent short-term predictor of HCC in CHB patients [84].…”

Section: M2bpgi For Hcc Prediction In Chbmentioning

confidence: 97%

Novel Biomarkers of Hepatitis B and Hepatocellular Carcinoma: Clinical Significance of HBcrAg and M2BPGi

Baudi

Tanaka

2020

IJMS

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The hepatitis B virus (HBV) cannot be removed completely from infected hepatocytes, owing to the presence of intrahepatic covalently closed circular DNA (cccDNA). As chronic hepatitis B (CHB) can progress to cirrhosis and hepatocellular carcinoma (HCC), predicting HCC development in high-risk patients with high viral replicative activity or advanced fibrosis is important. Novel serological biomarkers reflect intrahepatic viral replicative activity or the progression of liver fibrosis, indicating non-invasive alternatives to liver biopsy: (1) Hepatitis B core-related antigen (HBcrAg) correlates with serum HBV DNA and intrahepatic cccDNA. In CHB patients, a decrease in HBcrAg is associated with favorable outcomes. HBcrAg can predict HCC occurrence or recurrence. (2) Measurement of the Mac-2 binding protein glycosylation isomer (M2BPGi) has been introduced for the evaluation of liver fibrosis. An increase in M2BPGi in CHB patients is related to the progression of liver fibrosis and high potential (risk) of HCC development. Here, we describe the clinical applications of HBcrAg and M2BPGi in CHB patients. Additionally, because new potential therapeutic agents that eliminate intrahepatic cccDNA are being developed, monitoring of HBcrAg or M2BPGi might be suitable for evaluating therapeutic effects and the clinical outcomes. In conclusion, these would be appropriate surrogate markers for predicting disease progression.

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Serum Levels of M2BPGi as Short-Term Predictors of Hepatocellular Carcinoma in Untreated Chronic Hepatitis B Patients

Cited by 28 publications

References 38 publications

Mac‐2 Binding Protein Glycosylation Isomer as a Hepatocellular Carcinoma Marker in Patients With Chronic Hepatitis B or C Infection

Mac‐2 Binding Protein Glycosylation Isomer as a Hepatocellular Carcinoma Marker in Patients With Chronic Hepatitis B or C Infection

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

Novel Biomarkers of Hepatitis B and Hepatocellular Carcinoma: Clinical Significance of HBcrAg and M2BPGi

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