A Study on Serum Protein Tracking in Patients with Low Levels of HBsAg Undergoing Treatment for Chronic Hepatitis B with a Combination of Tenofovir Disoproxil Fumarate and Pegylated Interferon

Abstract

Background: A negative hepatitis B surface antigen (HBsAg) level is indicative of a ‘clinical cure’. Sequential treatment with nucleotide analogues in combination with interferon rapidly reduces HBsAg levels in some of the most favored populations, although the exact mechanism remains unclear. Objectives: In this study, we aimed to investigate the differences in biomarkers before and after treatment and to identify highly sensitive and specific biomarkers to predict the efficacy of combination therapy with tenofovir disoproxil fumarate (TDF) and pegylated interferon-α (PEG-IFN-α). Methods: By using data-independent acquisition (DIA)-based liquid chromatography-mass spectrometry (LC-MS/MS) technique, we analyzed serum protein mass spectra from 25 patients with chronic hepatitis B (CHB) who experienced a rapid reduction in HBsAg levels after baseline samples prior to therapy, at week 12 of treatment, and at week 24 of treatment. For further analysis, proteins with a fold change of ≥ 2 or ≤ 0.5 and a P-value < 0.05 were considered significantly differentially expressed. Results: A total of 3,174 proteins were identified in our study, of which 54 were differentially expressed between the serum samples of combination therapy before treatment and those of combination therapy at week 12 of treatment, and 154 that were differentially expressed between the samples of combination therapy before treatment and those of combination therapy at week 24 of treatment. Conclusions: To the best of our knowledge, we are the first to reveal differences in molecular profiles in serum at different stages of combination therapy using DIA-based quantitative proteomic analyses, which may provide fundamental information for further detailed investigation of the molecular mechanisms underlying the rapid response to combination therapy.