title: Serum metabolomic signatures discriminate early liver inflammation and fibrosis stages in patients with chronic hepatitis B.
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.
authors: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003 Hangzhou, People's Republic of China.|Department of Infectious Diseases, Zhejiang Provincial People's Hospital, 310014 Hangzhou, People's Republic of China.
authors: Haijun
authors: H
authors: Huang
authors: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003 Hangzhou, People's Republic of China.
authors: Zeyu
authors: Z
authors: Sun
authors: Department of Infectious Diseases, Zhejiang Provincial People's Hospital, 310014 Hangzhou, People's Republic of China.
authors: Hongying
authors: H
authors: Pan
authors: Department of Infectious Diseases, Zhejiang Provincial People's Hospital, 310014 Hangzhou, People's Republic of China.
authors: Meijuan
authors: M
authors: Chen
authors: Department of Infectious Diseases, Zhejiang Provincial People's Hospital, 310014 Hangzhou, People's Republic of China.
authors: Yongxi
authors: Y
authors: Tong
authors: Department of Infectious Diseases, Zhejiang Provincial People's Hospital, 310014 Hangzhou, People's Republic of China.
authors: Jiajie
authors: J
authors: Zhang
authors: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003 Hangzhou, People's Republic of China.
authors: Deying
authors: D
authors: Chen
authors: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003 Hangzhou, People's Republic of China.
authors: Xiaoling
authors: X
authors: Su
authors: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003 Hangzhou, People's Republic of China.
authors: Lanjuan
authors: L
authors: Li
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D019694:Hepatitis B, Chronic / Q000097:blood / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000473:pathology*; D008244:Lysophosphatidylcholines / Q000097:blood; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D010713:Phosphatidylcholines / Q000097:blood; D010716:Phosphatidylinositols / Q000097:blood; D010718:Phosphatidylserines / Q000097:blood; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D008244:Lysophosphatidylcholines; D010713:Phosphatidylcholines; D010716:Phosphatidylinositols; D010718:Phosphatidylserines