Serum M2BPGi level is a novel predictive biomarker for the responses to pegylated interferon‐α treatment in HBeAg‐positive chronic hepatitis B patients

Abstract

Serum Mac‐2‐binding protein glycosylation isomer (M2BPGi) level was found to be a useful prognostic marker for hepatitis B e antigen (HBeAg)‐positive chronic hepatitis B (CHB) patients treated with nucleoside/nucleotide analogs (NUCs) therapy, and the aim of our study is to evaluate the clinical implementation of M2BPGi level in the prediction of antiviral responses to pegylated‐interferon‐α (PEG‐IFN‐α) treatment in HBeAg‐positive CHB patients. Ninety‐six CHB patients who received PEG‐IFN‐α treatment for at least 48 weeks were recruited. The serum M2BPGi, alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), HBeAg, and HBV DNA levels at baseline, weeks 4, 12, and 24 after PEG‐IFN‐α treatment were determined and their associations with antiviral responses were evaluated and the virological response (VR) rate and serological response (SR) rate after 48 weeks of treatment were 65.6% and 35.4%, respectively. Baseline serum M2BPGi level was significantly different between VR and non‐VR (P = 0.002) or SR and non‐SR groups (P = 0.012). Multivariate analyses suggested that baseline serum M2BPGi level was independently associated with VR and SR of PEG‐IFN‐α treatment at week 48. The area under the ROC curve (AUC) of baseline M2BPGi was 0.682 in predicting VR, which was superior to HBsAg (AUC = 0.566) or HBV DNA (AUC = 0.567). The AUC of baseline M2BPGi in predicting SR was 0.655, which was also higher than that of HBsAg (AUC = 0.548) or HBV DNA (AUC = 0.583). These results suggested that baseline serum M2BPGi level was a novel predictor of VR and SR for PEG‐IFN‐α treatment in HBeAg‐positive CHB patients.

Reduction of hepatitis B surface antigen in sequential versus add-on pegylated interferon to nucleoside/nucleotide analogue therapy in HBe-antigen-negative chronic hepatitis B patients: A pilot study

“…Observing the time course of ALT during PEG-IFN therapy, we found that HBsAg reduction levels from the beginning of therapy to one year after PEG-IFN therapy were significantly correlated with the maximum ALT levels during PEG-IFN therapy (P=0.002) ( Figure 3A). In patients whose ALT levels were elevated by more than 50 U/L during PEG-IFN therapy, HBsAg levels were reduced by - [18]. However, we could not identify a useful predictive clinical factor for HBsAg reduction during PEG-IFN therapy in this study.…”

Usefulness of serum Mac-2 binding protein glycosylation isomer in patients undergoing hepatectomy: A case controlled study

“…As the serum M2BPGi level is supposed to be more sensitive in reflecting hepatic fibrosis or liver damage according to recent reports, we hypothesized the additional significance of this new marker in the present study. Some reports revealed that the changes of M2BPGi before and after anti-viral hepatitis treatments reflected its high sensitivity in the evaluation of treatment effects [18,22,35,36].…”

Induction of interleukin 6 impairs the anti‐HBV efficiency of IFN‐α in human hepatocytes through upregulation of SOCS3

“…Chronic hepatitis B virus (CHB) infection is correlated with high risk of developing liver fibrosis, cirrhosis, and hepatocellular carcinoma . Currently, interferon‐α (IFN‐α) is one of the most commonly used treatment for HBV infection . Antiviral responses to IFN‐α are mediated by many antiviral proteins induced through activation of the JAK‐STAT signaling pathway .…”

“…4,5 Currently, interferon-α (IFN-α) is one of the most commonly used treatment for HBV infection. 6,7 Antiviral responses to IFN-α are mediated by many antiviral proteins induced through activation of the JAK-STAT signaling pathway. 8 The activated STAT1/2 heterodimerize with interferon regulatory factor 9 (IRF-9) to form the interferon-stimulated gene factor 3 (ISGF-3) transcription factor complexes and then translocate into the nucleus, where they bind to the interferon-stimulated response element (ISRE) in the promoter of interferon-stimulated genes (ISGs), including myxovirus resistance A (MxA), oligoadenylate synthetase (OAS), and RNA-activated protein kinase (PKR), all of which restrict HBV replication in human hepatocytes.…”