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

Hsu, Yao‐Chun; Jun, Tomi; Huang, Yen‐Tsung; Yeh, Ming‐Lun; Lee, Chia‐Long; Ogawa, S.; Cho, Shu-Hsien; Lin, Jaw‐Town; Yu, Ming‐Lung; Nguyen, Mindie H.; Tanaka, Yasuhito

doi:10.1111/apt.15006

Cited by 29 publications

(25 citation statements)

References 42 publications

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“…First, it is increasingly apparent that M2BPGi is not solely a marker of liver fibrosis. M2BPGi levels are elevated in the setting of nonspecific acute liver injury, and M2BPGi levels decline quickly with antiviral treatment for HBV and HCV, too quickly to be due to regression of fibrosis . Bekki et al demonstrated that hepatic stellate cells produce M2BPGi in vitro and that M2BPGi signaling between hepatic stellate cells and Kupffer cells may promote a fibrogenic program.…”

Section: Discussionmentioning

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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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%

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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“…For example, macrophage‐specific activation marker sCD163 was proved to predict significant portal hypertension accurately combined with ELF results . Biomarker such as serum Mac‐2‐binding protein glycosylation isomer (M2BPGi) could predict HCC in nucleos(t)ide analogues‐treated CHB patients . The probability of combing those markers with LSM to predict HCC in CHB patients need to be explored.…”

Section: Discussionmentioning

confidence: 99%

Improvement in enhanced liver fibrosis score and liver stiffness measurement reflects lower risk of hepatocellular carcinoma

Liang

Wong

Tse

et al. 2019

Aliment Pharmacol Ther

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Background:The Liver stiffness measurement hepatocellular carcinoma (LSM-HCC) score predicts HCC accurately in patients with chronic hepatitis B (CHB). Aim:To assess the ability of LSM-HCC combined with enhanced liver fibrosis (ELF) score to predict HCC in CHB patients who received anti-viral treatment. Methods: CHB patients who had transient elastography examinations in 2006-2013 with intermediate and high risk of HCC by LSM-HCC score (ie 11 or above) were assessed by repeat transient elastography at least 3 years later. ELF score was assessed by retrieving the stored serum samples 4 weeks within transient elastography examination. The primary endpoint was the cumulative incidence of HCC. Results: A total of 453 CHB patients (mean age 51.7 ± 10.3 years; male 74.4%) were recruited, 45 patients (9.9%) developed HCC during the mean follow-up of 56 months.Regarding LSM-HCC score, 71.4%, 24.3% and 4.3% of patients had LSM-HCC score improved, remained static and deteriorated respectively; whereas 36.9%, 57.8% and 5.3% of patients had ELF score improved, remained static and deteriorated respectively. The sensitivity (86.7%) and negative predictive value (NPV) (95.3%) of combined LSM-HCC and ELF score were higher than that of each score alone.Kaplan-Meier analysis showed that ELF score would help further differentiate the HCC risk in patients with intermediate risk by LSM-HCC score (P = 0.026), but not in patients with high risk by LSM-HCC score (P = 0.770). Conclusions:The two-step algorithm combining LSM-HCC score and ELF score could improve the accuracy of predicting HCC of CHB patients receiving anti-viral treatment.

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“…In patients with undetectable HBV DNA during NA therapy, a higher pre-treatment M2BPGi level is associated with an increased risk of HCC development [86,88]. Cheung et al compared 57 NA-treated patients, with undetectable HBV DNA and HCC development, with 57 controls.…”

Section: M2bpgi and Its Characteristicsmentioning

confidence: 99%

“…Moreover, in patients with cirrhosis, the baseline M2BPGi level was associated with HCC occurrence, while the M2BPGi levels at year 1 or 2 were not independently predictive. As a result, a risk score for HCC occurrence was developed using the baseline M2BPGi, age, and body mass index at 3, 5, and 10 years, respectively [86]. Shinkai et al also reported that serum M2BPGi levels ≥1.215 C.O.I.…”

Section: M2bpgi For Hcc Prediction In Chbmentioning

confidence: 99%

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

Cited by 29 publications

References 42 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

Improvement in enhanced liver fibrosis score and liver stiffness measurement reflects lower risk of hepatocellular carcinoma

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

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