Abstract
Chronic HBV (CHB) infected patients with intermediate necroinflammation and fibrosis are recommended to receive antiviral treatment. However, other than liver biopsy, there is a lack of sensitive and specific objective method to determine the necroinflammation and fibrosis stages in CHB patients. This study aims to identify unique serum metabolomic profile associated with histological progression in CHB patients and to develop novel metabolite biomarker panels for early CHB detection and stratification. A comprehensive metabolomic profiling method was established to compare serum samples collected from health donor (n = 67), patients with mild (G < 2 and S < 2, CHB1, n = 52) or intermediate (G ≥ 2 or S ≥ 2, CHB2, n = 36) necroinflammation and fibrosis. Multivariate models were developed to differentiate CHB1 and CHB2 from controls. A set of CHB-associated biomarkers was identified, including lysophosphatidylcholines, phosphatidylcholines, phosphatidylinositol, phosphatidylserine, and bile acid metabolism products. Stratification of CHB1 and CHB2 patients by a simple logistic index, the PIPSindex, based on phosphatidylinositol (PI) and phosphatidylserine (PS), was achieved with an AUC of 0.961, which outperformed all currently available markers. A panel of serum metabolites that differentiate health control, CHB1 and CHB2 patients has been identified. The proposed metabolomic biosignature has the potential to be used as indicator for antiviral treatment for CHB management.
Highlights
Patients with chronic hepatitis B (CHB) are at high risk of developing hepatic decompensation, liver cirrhosis, hepatocellular carcinoma (HCC) and end-stage liver disease (ESLD)[1,2]
The current guidelines proposed by American Association for the Study of Liver Diseases (AASLD), the European Association for the Study of the Liver (EASL) and the Asian-Pacific Association for the Study of the Liver (APASL) for antiviral treatment predominantly rely on monitoring alanine aminotransferase (ALT) level[7,8,9]
The majority of published serum biomarkers were proposed for detecting significant liver fibrosis in CHB patients[21], only a few serum biomarkers were proposed to assist in the detection
Summary
Patients with chronic hepatitis B (CHB) are at high risk of developing hepatic decompensation, liver cirrhosis, hepatocellular carcinoma (HCC) and end-stage liver disease (ESLD)[1,2]. Recent metabolomic studies based on ultra-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS) have helped to develop diagnostic or prognostic biomarkers for a variety of liver diseases[24,25,26,27]. We aimed to develop multivariate models using high coverage UPLC-HRMS metabolomics data to differentiate patients with mild or significant inflammation and fibrosis stages within CHB cohort with ALT level smaller than 2X ULN and healthy controls. Based on this model, we further aimed to develop serum metabolite markers for CHB stage stratification
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
