Serum Proteomic Changes as Candidate Biomarkers of Intermediate Liver Fibrosis in Chronic Hepatitis B Infection

Chronic hepatitis B (CHB) is a major global health burden. Liver fibrosis, an insidious process, is the main histopathological change in CHB that might lead to the end-stage liver disease if left untreated. The intermediate liver fibrosis (S2) is the optimal time to start antiviral therapy. The aim of the present study was to examine the proteomic changes in patients with CHB at different fibrotic stages, with a view to identify future serum biomarkers for S2. Ninety CHB patients were grouped into mild (S0-1), intermediate (S2), and severe liver fibrosis (S3-4) (61 men and 29 women; age 25-63 years). Isobaric tagging for relative and absolute quantitation was applied to screen proteins differentially expressed among the patient groups. Another 46 patients with CHB (age 25-59 years; 31 men and 15 women), and 16 healthy controls (age 26-61 years; 11 men and 5 women) were enrolled in a validation group. Enzyme-linked immunosorbent assay was used to verify the diagnostic value of the candidate biomarkers. We found 139 proteins that were differentially expressed between various fibrotic stage-paired comparisons. Five protein candidates were selected as potential biomarkers of S2 for further verification. Notably, ficolin-2 (FCN2) and carboxypeptidase B2 (CPB2) showed differential expression between patients and healthy controls. In conclusion, serum proteomic changes reported here offer new molecular leads for future research on biomarker candidates to identify liver fibrotic stages in CHB. In particular, FCN2 and CPB2 warrant further research on their possible mechanistic involvement in CHB pathogenesis.