title: Screening for serum biomarkers in patients with chronic hepatitis B with hepatitis B surface antigen seroclearance, following pegylated interferon alpha therapy.
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.
authors.affiliation: Qingdao Hospital for Infectious Diseases, Qingdao, Shandong 266033, P.R. China.
authors.forename: Zheling
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Qingdao Hospital for Infectious Diseases, Qingdao, Shandong 266033, P.R. China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Li
authors.affiliation: Qingdao Hospital for Infectious Diseases, Qingdao, Shandong 266033, P.R. China.
authors.forename: Changhe
authors.initials: C
authors.lastname: Shi
authors.affiliation: Qingdao Hospital for Infectious Diseases, Qingdao, Shandong 266033, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Qingdao Hospital for Infectious Diseases, Qingdao, Shandong 266033, P.R. China.
authors.forename: Ru
authors.initials: R
authors.lastname: Chen
authors.affiliation: Qingdao Hospital for Infectious Diseases, Qingdao, Shandong 266033, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Qingdao Hospital for Infectious Diseases, Qingdao, Shandong 266033, P.R. China.
authors.forename: Qingshun
authors.initials: Q
authors.lastname: Hou
authors.affiliation: Qingdao Hospital for Infectious Diseases, Qingdao, Shandong 266033, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ke
authors.affiliation: Qingdao Hospital for Infectious Diseases, Qingdao, Shandong 266033, P.R. China.
authors.forename: Tianli
authors.initials: T
authors.lastname: Fan
authors.affiliation: Qingdao Hospital for Infectious Diseases, Qingdao, Shandong 266033, P.R. China.
authors.forename: Zirong
authors.initials: Z
authors.lastname: Wen
authors.affiliation: Qingdao Hospital for Infectious Diseases, Qingdao, Shandong 266033, P.R. China.
authors.forename: Xinjie
authors.initials: X
authors.lastname: Hao
authors.affiliation: Qingdao Hospital for Infectious Diseases, Qingdao, Shandong 266033, P.R. China.
authors.forename: Naifang
authors.initials: N
authors.lastname: Qu
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood*; D061505:Cell Surface Display Techniques; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000097:blood* / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D019151:Peptide Library; D010455:Peptides / Q000097:blood; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D006514:Hepatitis B Surface Antigens; D016898:Interferon-alpha; D019151:Peptide Library; D010455:Peptides; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a