Screening for serum biomarkers in patients with chronic hepatitis B with hepatitis B surface antigen seroclearance, following pegylated interferon alpha therapy

Wang,Zheling; Li,Xiaofei; Shi,Changhe; Zhang,Min; Chen,Ru; Wu,Wei; Hou,Qingshun; Ke,Wei; Fan,Tianli; Wen,Zirong; Hao,Xinjie; Qu,Naifang

doi:10.3892/mmr.2014.2670

January-2015 Volume 11 Issue 1

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

January-2015 Volume 11 Issue 1

Full Size Image

Article

Screening for serum biomarkers in patients with chronic hepatitis B with hepatitis B surface antigen seroclearance, following pegylated interferon alpha therapy

Authors:
- Zheling Wang
- Xiaofei Li
- Changhe Shi
- Min Zhang
- Ru Chen
- Wei Wu
- Qingshun Hou
- Wei Ke
- Tianli Fan
- Zirong Wen
- Xinjie Hao
- Naifang Qu
View Affiliations / Copyright

Affiliations: Qingdao Hospital for Infectious Diseases, Qingdao, Shandong 266033, P.R. China
Pages: 427-433
|
Published online on: October 16, 2014

https://doi.org/10.3892/mmr.2014.2670
Expand metrics +

Abstract

Chronic hepatitis B (CHB) is one of the most common infectious disease worldwide and a leading cause of death. Hepatitis B surface antigen (HBsAg) has previously been proven to be a steady biomarker that may be used to predict clinical outcomes. The amount of circulating HBsAg has been reported to reflect the number of infected hepatocytes. An advantage of pegylated interferon alpha (peg‑IFN‑α) is that as a finite course of therapy, it can potentially lead to sustained disease remission in subsequent decades. HBsAg seroclearance can reportedly be achieved in some hepatitis B patients treated with peg‑IFN‑α; this is a major advantage of IFN‑α, as compared with nucleoside analogue treatment. In the present study, a random phage display peptide library was used to screen for potential serum peptide biomarkers in predicting which patients with CHB would exhibit HBsAg seroclearance, following 48 weeks of peg‑IFN‑α therapy. A total of 30 patients with CHB who achieved HBsAg seroclearance following peg‑IFN‑α therapy and an additional 30 age‑, gender‑, hepatitis B e antigen (HBeAg) status‑ and hepatitis B virus genotype‑matched patients with CHB without HBsAg seroclearance following peg‑IFN‑α therapy, were enrolled as a discovery cohort. In the discovery/screening phase, 17/20 of the randomly selected phage clones, exhibited a specific reaction with purified sera immunoglobulin G from the HBsAg clearance group, and 13/17 positive phage clones came from the same phage clone, with the inserted peptide sequence ETCRASCINESA (named IFNC1). In the validation phase, phage‑ELISA results showed that the positive reaction rate of the IFNC1 peptide phage clone was 92.0% with the HBsAg seroclearance group (n=50), which was significantly higher, as compared with the randomly selected HBsAg non‑clearance group (12.0%, n=50) and the healthy control group (8.0%, n=50). In conclusion, the newly identified mimic peptide IFNC1 showed a high predictive validity HBsAg seroclearance in patients with CHB, following peg‑IFN‑α therapy. Therefore IFNC1 may be a potential serum biomarker, which could be used to predict the treatment outcomes of peg‑IFN‑α therapy.

View Figures

View References

1	Liaw YF and Chu CM: Hepatitis B virus infection. Lancet. 373:582–592. 2009. View Article : Google Scholar : PubMed/NCBI
2	Dusheiko G: Treatment of HBeAg positive chronic hepatitis B: interferon or nucleoside analogues. Liver Int. 33:137–150. 2013. View Article : Google Scholar : PubMed/NCBI
3	Blumberg BS, Alter HJ and Visnich S: A “new” antigen in leukemia sera. JAMA. 191:541–546. 1965.
4	Martinot-Peignoux M, Lapalus M, Asselah T and Marcellin P: HBsAg quantification: useful for monitoring natural history and treatment outcome. Liver Int. 34:97–107. 2014. View Article : Google Scholar : PubMed/NCBI
5	Smith GP: Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science. 228:1315–1317. 1985. View Article : Google Scholar : PubMed/NCBI
6	Samoylova TI, Morrison NE, Globa LP and Cox NR: Peptide phage display: opportunities for development of personalized anti-cancer strategies. Anticancer Agents Med Chem. 6:9–17. 2006.PubMed/NCBI
7	Sergeeva A, Kolonin MG, Molldrem JJ, Pasqualini R and Arap W: Display technologies: application for the discovery of drug and gene delivery agents. Adv Drug Deliv Rev. 58:1622–1654. 2006. View Article : Google Scholar : PubMed/NCBI
8	Liaw YF, Leung N, Kao JH, et al: Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update. Hepatol Int. 2:263–283. 2008. View Article : Google Scholar
9	Zhang Z, Xu L and Wang Z: Screening serum biomarkers for early primary hepatocellular carcinoma using a phage display technique. J Clin Lab Anal. 25:402–408. 2011. View Article : Google Scholar : PubMed/NCBI
10	Wang M, Yi XY, Li XP, Zhou DM, Larry M and Zeng XF: Phage displaying peptides mimic schistosoma antigenic epitopes selected by rat natural antibodies and protective immunity induced by their immunization in mice. World J Gastroenterol. 11:2960–2966. 2005. View Article : Google Scholar
11	Wang Y, Zhao C, Zhang L, et al: Predictive value of interferon-gamma inducible protein 10kD for hepatitis B e antigen clearance and hepatitis B surface antigen decline during pegylated interferon alpha therapy in chronic hepatitis B patients. Antiviral Res. 103:51–59. 2014. View Article : Google Scholar
12	Tanwar S and Dusheiko G: Is there any value to hepatitis B virus genotype analysis? Curr Gastroenterol Rep. 14:37–46. 2012. View Article : Google Scholar : PubMed/NCBI
13	Goffinet M, Chinestra P, Lajoie-Mazenc I, Medale-Giamarchi C, Favre G and Faye JC: Identification of a GTP-bound Rho specific scFv molecular sensor by phage display selection. BMC Biotechnol. 8:342008. View Article : Google Scholar : PubMed/NCBI
14	Nizak C, Monier S, del Nery E, Moutel S, Goud B and Perez F: Recombinant antibodies to the small GTPase Rab6 as conformation sensors. Science. 300:984–987. 2003. View Article : Google Scholar : PubMed/NCBI
15	Hadziyannis SJ: Treatment paradigms on hepatitis B e antigen-negative chronic hepatitis B patients. Expert Opin Investig Drugs. 16:777–786. 2007. View Article : Google Scholar : PubMed/NCBI
16	Merican I, Guan R, Amarapuka D, et al: Chronic hepatitis B virus infection in Asian countries. J Gastroenterol Hepatol. 15:1356–1361. 2000. View Article : Google Scholar : PubMed/NCBI
17	Sievert W, Altraif I, Razavi HA, et al: A systematic review of hepatitis C virus epidemiology in Asia, Australia and Egypt. Liver Int. 31(Suppl 2): 61–80. 2011. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Screening for serum biomarkers in patients with chronic hepatitis B with hepatitis B surface antigen seroclearance, following pegylated interferon alpha therapy

This article is mentioned in:

Abstract

Figure 1

Related Articles