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Circulating metabolites are associated with persistent elevations of ALT in patients with chronic hepatitis B with complete viral suppression
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  • Jian Sun,
  • Dekai Zheng,
  • Changhao Cheng,
  • Yanhua Tang,
  • Zhixin Fang,
  • Xuelian Gao,
  • Yuchuan Chen,
  • * Qiuhong,
  • Kaifeng Wang,
  • Heqi Zhou,
  • Zhixian Lan
Jian Sun
Southern Medical University Nanfang Hospital Guangdong Provincial Key Laboratory of Viral Hepatitis Research

Corresponding Author:[email protected]

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Dekai Zheng
Southern Medical University Nanfang Hospital Guangdong Provincial Key Laboratory of Viral Hepatitis Research
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Changhao Cheng
Southern Medical University Nanfang Hospital Guangdong Provincial Key Laboratory of Viral Hepatitis Research
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Yanhua Tang
First Affiliated Hospital of University of South China
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Zhixin Fang
Southern Medical University Nanfang Hospital Guangdong Provincial Key Laboratory of Viral Hepatitis Research
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Xuelian Gao
Southern Medical University Nanfang Hospital Guangdong Provincial Key Laboratory of Viral Hepatitis Research
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Yuchuan Chen
Southern Medical University Nanfang Hospital Guangdong Provincial Key Laboratory of Viral Hepatitis Research
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* Qiuhong
Southern Medical University Nanfang Hospital Guangdong Provincial Key Laboratory of Viral Hepatitis Research
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Kaifeng Wang
Southern Medical University Nanfang Hospital Guangdong Provincial Key Laboratory of Viral Hepatitis Research
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Heqi Zhou
Southern Medical University Nanfang Hospital Guangdong Provincial Key Laboratory of Viral Hepatitis Research
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Zhixian Lan
Southern Medical University Nanfang Hospital Guangdong Provincial Key Laboratory of Viral Hepatitis Research
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Abstract

Background & Aims: Hepatitis B virus (HBV) can be completely suppressed after antiviral treatment; however, some patients with chronic hepatitis B (CHB) still exhibit elevated alanine aminotransferase (ALT) levels and sustained disease progression. The aim of this study was to provide novel insights into the mechanism and potential predictive biomarkers of persistently elevated ALT (PeALT) in patients with CHB after complete viral inhibition. Methods: CHB Patients with undetectable HBV DNA at least 12 months after antiviral treatment were enrolled from a prospective, observational cohort. Correlations between plasma metabolites and the risk of elevated ALT were examined using multivariate logistic regression. Results: Of the 1238 patients with CHB who achieved complete viral suppression, 40 (3.23%) had PeALT levels during follow-up (median follow-up: 2.42 years). Additionally, 40 patients with persistently normal ALT (PnALT) levels were matched 1:1 as controls. Ser-Phe-Ala (variable importance in projection [VIP] = 4.28), Lys-Ala-Leu-Glu (VIP = 4.49), 3-methylhippuric acid (VIP = 3.04), 3-methylxanthine (VIP = 2.62), and 7-methylxanthine (VIP = 3.35) were identified as critical differential metabolites between the two groups and independently associated with PeALT risk. Ser-Phe-Ala and Lys-Ala-Leu-Glu levels could be used to discriminate patients with PeALT from those with PnALT. Furthermore, N-acetyl-l-methionine (NALM) demonstrated the strongest negative correlation with ALT levels. NALM supplementation alleviated liver injury and hepatic necrosis induced by carbon tetrachloride in mice. Conclusions: Changes in circulating metabolites may contribute to PeALT levels in patients with CHB who have achieved complete viral suppression after antiviral treatment.
22 Feb 2024Submitted to Journal of Medical Virology
22 Feb 2024Assigned to Editor
22 Feb 2024Submission Checks Completed
22 Feb 2024Review(s) Completed, Editorial Evaluation Pending
08 Mar 2024Reviewer(s) Assigned
15 Apr 2024Editorial Decision: Revise Major