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.
Highlights
Liver fibrosis is a pathology common to various liver injuries, characterized by excessive deposition of extracellular matrix, and is an inevitable process in the development of chronic hepatitis to cirrhosis and liver cancer [1]
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
We found that autoantibodies against aminoacylase-1 (ACY1), histidine triad nucleotide-binding protein 1 (HINT1), peroxiredoxin 3 (PRDX3), heat shock protein 70 (HSPA6), apoptosis-inducing factor (AIF), regucalcin (RGN), centromere protein F (CENPF) and ENO1 had diagnostic value for distinguishing patients with cirrhosis from chronic hepatitis using serological proteome and protein microarray analyses, with area under the curve (AUC) values greater than or close to 0.7 [10, 11]
Summary
Liver fibrosis is a pathology common to various liver injuries, characterized by excessive deposition of extracellular matrix, and is an inevitable process in the development of chronic hepatitis to cirrhosis and liver cancer [1]. Circulating biomarkers have good prospects for research because they are accessible and noninvasive [2]; the limitations of current biomarker models include an indeterminate range, and the ability to only detect binomial outcomes such as the presence or absence of cirrhosis. Interpretation of these models in the clinical setting requires careful attention to comorbidities, as well as knowledge about the population prevalence of fibrosis (pre-test probability) [6]
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