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.

Chronic hepatitis B surface antigen seroclearance‐related immune factors

“…Recently, in studies on new treatments that include a combination of nucleotide drugs and IFNs, we showed that patients with HBeAg‐positive CHB and a partial viral response to NUC therapy can achieve undetectable HBsAg and HBeAg seroconversion after switching to PegIFN‐2α treatment . Genetic variation in STAT and IFNC1can predict the response to IFN‐α therapy. It was reported that STAT4 rs7574865 is a reliable predictor of the response to IFN‐α therapy .…”

“…A number of studies have indicated that using a fixed course of polyethylene glycol-modified IFN can improve the immune function, the sustained response rate (HBeAg seroconversion in some patients appears even as HBsAg seroconversion) and the long-term prognosis of patients with CHB. [67][68][69] A recent study has described a new type of IFN, namely, PegIFN-lambda-1a (Lambda), a type III IFN that has antiviral activity against HBV and hepatitis C virus in vitro. Treatment with Lambda has been shown to exert stronger early effects on HBV-DNA and quantitative HBsAg.…”

“…73 A study by Wang et al found that the inserted peptide sequence ETCRASCINESA (named IFNC1) is a potential serum biomarker that could be used to predict the treatment outcomes of PegIFN-α therapy and has high predictive validity for HBsAg seroclearance. 67 However, IFN has many constraints, including obvious adverse reactions and the need for injection. Furthermore, IFN is not suitable for patients with compromised liver function.…”