Hepatocellular Carcinoma and Hepatitis B Surface Protein

Overview

Journal World J Gastroenterol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2016 Feb 16

PMID 26877602

Citations 30

Authors

Yong-Wei Li

Feng-Cai Yang

Hui-Qiong Lu

Jiong-Shan Zhang

Affiliations

Soon will be listed here.

Abstract

The tumorigenesis of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) has been widely studied. HBV envelope proteins are important for the structure and life cycle of HBV, and these proteins are useful for judging the natural disease course and guiding treatment. Truncated and mutated preS/S are produced by integrated viral sequences that are defective for replication. The preS/S mutants are considered "precursor lesions" of HCC. Different preS/S mutants induce various mechanisms of tumorigenesis, such as transactivation of transcription factors and an immune inflammatory response, thereby contributing to HCC. The preS2 mutants and type II "Ground Glass" hepatocytes represent novel biomarkers of HBV-associated HCC. The preS mutants may induce the unfolded protein response and endoplasmic reticulum stress-dependent and stress-independent pathways. Treatments to inhibit hepatitis B surface antigen (HBsAg) and damage secondary to HBsAg or the preS/S mutants include antivirals and antioxidants, such as silymarin, resveratrol, and glycyrrhizin acid. Methods for the prevention and treatment of HCC should be comprehensive.

Citing Articles

Risk factors for hepatocellular carcinoma: an umbrella review of systematic review and meta-analysis.

Wang J, Qiu K, Zhou S, Gan Y, Jiang K, Wang D Ann Med. 2025; 57(1):2455539.

PMID: 39834076 PMC: 11753015. DOI: 10.1080/07853890.2025.2455539.

Factors Positively Correlated with Hepatitis B Surface Antigen Seroconversion in Chronic Hepatitis B.

Buechter M, Gunther A, Manka P, Gerken G, Kahraman A J Pers Med. 2024; 14(4).

PMID: 38673017 PMC: 11051014. DOI: 10.3390/jpm14040390.

Long-Term Outcomes after Switching to Tenofovir Alafenamide in Patients with Chronic Hepatitis B.

Nishikawa T, Matsui M, Onishi S, Ushiro K, Asai A, Kim S Int J Mol Sci. 2024; 25(4).

PMID: 38396921 PMC: 10888772. DOI: 10.3390/ijms25042245.

The role of Traditional Chinese medicine in anti-HBV: background, progress, and challenges.

Ge F, Yang Y, Bai Z, Si L, Wang X, Yu J Chin Med. 2023; 18(1):159.

PMID: 38042824 PMC: 10693092. DOI: 10.1186/s13020-023-00861-2.

The role of hepatitis B virus genome variations in HBV-related HCC: effects on host signaling pathways.

Shoraka S, Hosseinian S, Hasibi A, Ghaemi A, Mohebbi S Front Microbiol. 2023; 14:1213145.

PMID: 37588887 PMC: 10426804. DOI: 10.3389/fmicb.2023.1213145.

References

Li J, Liu Y, Wang Z, Liu K, Wang Y, Liu J . Subversion of cellular autophagy machinery by hepatitis B virus for viral envelopment. J Virol. 2011; 85(13):6319-33. PMC: 3126540. DOI: 10.1128/JVI.02627-10. View

Martinot-Peignoux M, Carvalho-Filho R, Lapalus M, Netto-Cardoso A, Lada O, Batrla R . Hepatitis B surface antigen serum level is associated with fibrosis severity in treatment-naïve, e antigen-positive patients. J Hepatol. 2013; 58(6):1089-95. DOI: 10.1016/j.jhep.2013.01.028. View

Leistner C, Gruen-Bernhard S, Glebe D . Role of glycosaminoglycans for binding and infection of hepatitis B virus. Cell Microbiol. 2007; 10(1):122-33. DOI: 10.1111/j.1462-5822.2007.01023.x. View

Reijnders J, Rijckborst V, Sonneveld M, Scherbeijn S, Boucher C, Hansen B . Kinetics of hepatitis B surface antigen differ between treatment with peginterferon and entecavir. J Hepatol. 2010; 54(3):449-54. DOI: 10.1016/j.jhep.2010.07.046. View

Pollicino T, Cacciola I, Saffioti F, Raimondo G . Hepatitis B virus PreS/S gene variants: pathobiology and clinical implications. J Hepatol. 2014; 61(2):408-17. DOI: 10.1016/j.jhep.2014.04.041. View

Gunther S, Fischer L, Pult I, Sterneck M, Will H . Naturally occurring variants of hepatitis B virus. Adv Virus Res. 1999; 52:25-137. DOI: 10.1016/s0065-3527(08)60298-5. View

Su I, Wang L, Hsieh W, Wu H, Teng C, Tsai H . The emerging role of hepatitis B virus pre-S2 deletion mutant proteins in HBV tumorigenesis. J Biomed Sci. 2014; 21:98. PMC: 4200140. DOI: 10.1186/s12929-014-0098-7. View

Hadziyannis S, Gerber M, Vissoulis C, Popper H . Cytoplasmic hepatitis B antigen in "ground-glass" hepatocytes of carriers. Arch Pathol. 1973; 96(5):327-30. View

Yaginuma K, Kobayashi M, Yoshida E, Koike K . Hepatitis B virus integration in hepatocellular carcinoma DNA: duplication of cellular flanking sequences at the integration site. Proc Natl Acad Sci U S A. 1985; 82(13):4458-62. PMC: 391120. DOI: 10.1073/pnas.82.13.4458. View

10.

Woltman A, Op den Brouw M, Biesta P, Shi C, Janssen H . Hepatitis B virus lacks immune activating capacity, but actively inhibits plasmacytoid dendritic cell function. PLoS One. 2011; 6(1):e15324. PMC: 3016396. DOI: 10.1371/journal.pone.0015324. View

11.

Zhu Y, Jin Y, Cai X, Bai X, Chen M, Chen T . Hepatitis B virus core protein variations differ in tumor and adjacent nontumor tissues from patients with hepatocellular carcinoma. Intervirology. 2011; 55(1):29-35. DOI: 10.1159/000322832. View

12.

Hildt E, Saher G, Bruss V, Hofschneider P . The hepatitis B virus large surface protein (LHBs) is a transcriptional activator. Virology. 1996; 225(1):235-9. DOI: 10.1006/viro.1996.0594. View

13.

Malhotra J, Miao H, Zhang K, Wolfson A, Pennathur S, Pipe S . Antioxidants reduce endoplasmic reticulum stress and improve protein secretion. Proc Natl Acad Sci U S A. 2008; 105(47):18525-30. PMC: 2587584. DOI: 10.1073/pnas.0809677105. View

14.

Wang H, Chang W, Chang W, Wu H, Huang W, Lei H . Hepatitis B virus pre-S2 mutant upregulates cyclin A expression and induces nodular proliferation of hepatocytes. Hepatology. 2005; 41(4):761-70. DOI: 10.1002/hep.20615. View

15.

Glebe D, Urban S, Knoop E, Cag N, Krass P, Grun S . Mapping of the hepatitis B virus attachment site by use of infection-inhibiting preS1 lipopeptides and tupaia hepatocytes. Gastroenterology. 2005; 129(1):234-45. DOI: 10.1053/j.gastro.2005.03.090. View

16.

Chisari F, Filippi P, Buras J, McLachlan A, Popper H, Pinkert C . Structural and pathological effects of synthesis of hepatitis B virus large envelope polypeptide in transgenic mice. Proc Natl Acad Sci U S A. 1987; 84(19):6909-13. PMC: 299194. DOI: 10.1073/pnas.84.19.6909. View

17.

Liu J, Yang H, Lee M, Lu S, Jen C, Wang L . Incidence and determinants of spontaneous hepatitis B surface antigen seroclearance: a community-based follow-up study. Gastroenterology. 2010; 139(2):474-82. DOI: 10.1053/j.gastro.2010.04.048. View

18.

Deguchi M, Yamashita N, Kagita M, Asari S, Iwatani Y, Tsuchida T . Quantitation of hepatitis B surface antigen by an automated chemiluminescent microparticle immunoassay. J Virol Methods. 2003; 115(2):217-22. DOI: 10.1016/j.jviromet.2003.10.002. View

19.

Wang L, Huang W, Lai M, Su I . Aberrant cyclin A expression and centrosome overduplication induced by hepatitis B virus pre-S2 mutants and its implication in hepatocarcinogenesis. Carcinogenesis. 2011; 33(2):466-72. DOI: 10.1093/carcin/bgr296. View

20.

Jaroszewicz J, Ho H, Markova A, Deterding K, Wursthorn K, Schulz S . Hepatitis B surface antigen (HBsAg) decrease and serum interferon-inducible protein-10 levels as predictive markers for HBsAg loss during treatment with nucleoside/nucleotide analogues. Antivir Ther. 2011; 16(6):915-24. DOI: 10.3851/IMP1866. View