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

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2020 Feb 7

PMID 32023902

Citations 18

Authors

Ian Baudi

Takako Inoue

Yasuhito Tanaka

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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Macrophage-2-Binding Protein Glycosylation Isomer (M2BPGi) and AGAP Score as Markers of Noninvasive Test for Liver Fibrosis versus FibroScan in Chronic Hepatitis B Patients: A Retrospective Observational Study.

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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.

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References

Ikeda M, Fujiyama S, Tanaka M, Sata M, Ide T, Yatsuhashi H . Risk factors for development of hepatocellular carcinoma in patients with chronic hepatitis C after sustained response to interferon. J Gastroenterol. 2005; 40(2):148-56. DOI: 10.1007/s00535-004-1519-2. View

Liu Y, Liang X . Progression and status of antiviral monitoring in patients with chronic hepatitis B: From HBsAg to HBV RNA. World J Hepatol. 2018; 10(9):603-611. PMC: 6177569. DOI: 10.4254/wjh.v10.i9.603. View

Hadziyannis E, Laras A . Viral Biomarkers in Chronic HBeAg Negative HBV Infection. Genes (Basel). 2018; 9(10). PMC: 6210948. DOI: 10.3390/genes9100469. View

Liu F, Wang X, Chen L, Hu P, Ren H, Hu H . Systematic review with meta-analysis: development of hepatocellular carcinoma in chronic hepatitis B patients with hepatitis B surface antigen seroclearance. Aliment Pharmacol Ther. 2016; 43(12):1253-61. DOI: 10.1111/apt.13634. View

Yamada N, Sanada Y, Tashiro M, Hirata Y, Okada N, Ihara Y . Serum Mac-2 binding protein glycosylation isomer predicts grade F4 liver fibrosis in patients with biliary atresia. J Gastroenterol. 2016; 52(2):245-252. DOI: 10.1007/s00535-016-1235-8. View

Lopatin U . Drugs in the Pipeline for HBV. Clin Liver Dis. 2019; 23(3):535-555. DOI: 10.1016/j.cld.2019.04.006. View

Yang H, Kao J . Looking into the crystal ball: biomarkers for outcomes of HBV infection. Hepatol Int. 2016; 10(1):99-101. DOI: 10.1007/s12072-015-9698-x. View

Bravo A, Sheth S, Chopra S . Liver biopsy. N Engl J Med. 2001; 344(7):495-500. DOI: 10.1056/NEJM200102153440706. View

Inoue T, Tanaka Y . Hepatitis B virus and its sexually transmitted infection - an update. Microb Cell. 2017; 3(9):420-437. PMC: 5354569. DOI: 10.15698/mic2016.09.527. View

10.

Shinkai N, Nojima M, Iio E, Matsunami K, Toyoda H, Murakami S . High levels of serum Mac-2-binding protein glycosylation isomer (M2BPGi) predict the development of hepatocellular carcinoma in hepatitis B patients treated with nucleot(s)ide analogues. J Gastroenterol. 2017; 53(7):883-889. DOI: 10.1007/s00535-017-1424-0. View

11.

Shinkai N, Kusumoto S, Murakami S, Ogawa S, Ri M, Matsui T . Novel monitoring of hepatitis B reactivation based on ultra-high sensitive hepatitis B surface antigen assay. Liver Int. 2016; 37(8):1138-1147. DOI: 10.1111/liv.13349. View

12.

Iloeje U, Yang H, Su J, Jen C, You S, Chen C . Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006; 130(3):678-86. DOI: 10.1053/j.gastro.2005.11.016. View

13.

Gane E . Future anti-HBV strategies. Liver Int. 2017; 37 Suppl 1:40-44. DOI: 10.1111/liv.13304. View

14.

Glebe D, Bremer C . The molecular virology of hepatitis B virus. Semin Liver Dis. 2013; 33(2):103-12. DOI: 10.1055/s-0033-1345717. View

15.

Seto W, Wong D, Fung J, Huang F, Liu K, Lai C . Linearized hepatitis B surface antigen and hepatitis B core-related antigen in the natural history of chronic hepatitis B. Clin Microbiol Infect. 2014; 20(11):1173-80. DOI: 10.1111/1469-0691.12739. View

16.

Zou X, Zhu M, Yu D, Li W, Zhang D, Lu F . Serum WFA -M2BP levels for evaluation of early stages of liver fibrosis in patients with chronic hepatitis B virus infection. Liver Int. 2016; 37(1):35-44. DOI: 10.1111/liv.13188. View

17.

Kim S, Heo J, Kim B, Park J, Kim D, Han K . Wisteria floribunda agglutinin-positive human Mac-2 binding protein predicts the risk of HBV-related liver cancer development. Liver Int. 2016; 37(6):879-887. DOI: 10.1111/liv.13341. View

18.

Honda M, Shirasaki T, Terashima T, Kawaguchi K, Nakamura M, Oishi N . Hepatitis B Virus (HBV) Core-Related Antigen During Nucleos(t)ide Analog Therapy Is Related to Intra-hepatic HBV Replication and Development of Hepatocellular Carcinoma. J Infect Dis. 2015; 213(7):1096-106. DOI: 10.1093/infdis/jiv572. View

19.

Chuaypen N, Posuwan N, Chittmittraprap S, Hirankarn N, Treeprasertsuk S, Tanaka Y . Predictive role of serum HBsAg and HBcrAg kinetics in patients with HBeAg-negative chronic hepatitis B receiving pegylated interferon-based therapy. Clin Microbiol Infect. 2017; 24(3):306.e7-306.e13. DOI: 10.1016/j.cmi.2017.07.016. View

20.

Jun T, Hsu Y, Ogawa S, Huang Y, Yeh M, Tseng C . Mac-2 Binding Protein Glycosylation Isomer as a Hepatocellular Carcinoma Marker in Patients With Chronic Hepatitis B or C Infection. Hepatol Commun. 2019; 3(4):493-503. PMC: 6442699. DOI: 10.1002/hep4.1321. View