Plasma Fibronectin Levels Identified via Quantitative Proteomics Profiling Predicts Hepatitis B Surface Antigen Seroclearance in Chronic Hepatitis B

Seroclearance of hepatitis B surface antigen (HBsAg) is a potentially achievable target of chronic hepatitis B (CHB). Plasma proteins relevant to HBsAg seroclearance remain undetermined. We prospectively recruited treatment-naive CHB patients with spontaneous HBsAg seroclearance and matched HBsAg-po...

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Bibliographic Details
Published in:The Journal of infectious diseases 2019-08, Vol.220 (6), p.940-950
Main Authors: Liu, Fen, Seto, Wai-Kay, Wong, Danny Ka-Ho, Huang, Fung-Yu, Cheung, Ka-Shing, Mak, Lung-Yi, Sharma, Rakesh, Zhang, Saisai, Fung, James, Lai, Ching-Lung, Yuen, Man-Fung
Format: Article
Language:English
Subjects:
Adult
Aged
Antigens
Blood Proteins - isolation & purification
Female
Fibronectin
Fibronectins - blood
Hepatitis
Hepatitis B
Hepatitis B surface antigen
Hepatitis B Surface Antigens - immunology
Hepatitis B, Chronic - immunology
Hepatitis B, Chronic - metabolism
Humans
Interferon
Male
Middle Aged
Plasma
Plasma - chemistry
Plasma proteins
Proteins
Proteomics
Quantitation
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Summary:Seroclearance of hepatitis B surface antigen (HBsAg) is a potentially achievable target of chronic hepatitis B (CHB). Plasma proteins relevant to HBsAg seroclearance remain undetermined. We prospectively recruited treatment-naive CHB patients with spontaneous HBsAg seroclearance and matched HBsAg-positive controls. Plasma protein profiling was performed using isobaric tags for relative and absolute quantitation-based proteomics, with the expression of candidate proteins validated in a separate cohort. The predictive value of fibronectin was assessed at 3 years, 1 year (Year -1) before, and at the time (Year 0) of HBsAg seroclearance. Four hundred eighty-seven plasma proteins were identified via proteomics, with 97 proteins showing altered expression. In the verification cohort (n = 90), median plasma fibronectin levels in patients with HBsAg seroclearance was higher than in controls (P = .009). In the longitudinal cohort (n = 164), patients with HBsAg seroclearance, compared with controls, had a higher median fibronectin levels at Year -1 (413.26 vs 227.95 µg/mL) and Year 0 (349.45 vs 208.72 µg/mL) (both P < .001). In patients with an annual HBsAg log reduction >0.5, Year -1 fibronectin level achieved an area under the receiving operator characteristic of 0.884 in predicting HBsAg seroclearance. Using proteomics-based technology, plasma fibronectin may be associated with HBsAg seroclearance and a potential predictor of "functional cure".
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiz223