Identification and Validation of Novel Serum Autoantibodies Biomarkers for Staging Liver Fibrosis in Patients With Chronic Hepatitis B

Abstract

Aim: Liver fibrosis monitoring is essential in patients with chronic hepatitis B (CHB). However, less robust, noninvasive diagnostic methods for staging liver fibrosis, other than liver biopsy, are available. Our previous study demonstrated a panel of cellular proteins recognized by autoantibodies that may have potential value in discrimination of CHB and liver cirrhosis. We aim to assess the diagnostic value of these serum autoantibodies for staging liver fibrosis.Methods: Candidate autoantigens were screened and assessed by microarray analysis in 96 healthy controls and 227 CHB patients with pre-treatment biopsy-proven METAVIR fibrosis score, comprising 69, 115, and 43 cases with S0-1, S2-3, and S4 stages, respectively. Autoantibodies with potential diagnostic value for staging liver fibrosis were verified by enzyme-linked immunosorbent assays (ELISA). Receiver operating characteristic curve was conducted to evaluate autoantibody performance.Results: Microarray analysis identified autoantigens CENPF, ACY1, HSPA6, and ENO1 with potential diagnostic value for liver fibrosis staging, among which CENPF and ACY1 were validated using ELISA. CENPF and ACY1 autoantibodies had area under the curve values of 0.746 and 0.685, 58.14 and 74.42% sensitivity, and 88.41 and 60.87% specificity, respectively, for discriminating liver fibrosis stages S4 and S0-1. The prevalence of CENPF and ACY1 autoantibodies was not correlated with age, sex or level of inflammation.Conclusions: Autoimmune responses may be elicited during progression of liver fibrosis, and serum autoantibodies may be a valuable biomarker for staging liver fibrosis deserving of further study.