慢性乙型肝炎进展的代谢指纹图谱：代谢组的变化和新的诊

StephenW

Metabolic fingerprint of progression of chronic hepatitis B: changes in the metabolome and novel diagnostic possibilities
Hien Thi Thu Nguyen  1 , Reinhard Wimmer  2 , Vang Quy Le  3 , Henrik Bygum Krarup  4   5   6
Affiliations
Affiliations

    1
    Department of Molecular Diagnostics, Aalborg University Hospital, Reberbansgade 15, 9000, Aalborg, Denmark.
    2
    Department of Chemistry and Bioscience, Aalborg University, Aalborg, Denmark.
    3
    CLAAUDIA, Aalborg University, Aalborg, Denmark.
    4
    Department of Molecular Diagnostics, Aalborg University Hospital, Reberbansgade 15, 9000, Aalborg, Denmark. [email protected].
    5
    Department of Medical Gastroenterology, Aalborg University Hospital, Aalborg, Denmark. [email protected].
    6
    Clinical Institute, Aalborg University, Aalborg, Denmark. [email protected].

    PMID: 33495863 DOI: 10.1007/s11306-020-01767-y

Abstract

Introduction: Chronic hepatitis B (CHB) affects 257 million individuals worldwide with an annual estimated mortality rate of 880,000 individuals. Accurate diagnosis of the stage of disease is difficult, and there is considerable uncertainty concerning the optimal point in time, when treatment should be started.

Objectives: By analyzing and comparing the metabolomes of patients at different stages of CHB and comparing them to healthy individuals, we want to determine the metabolic signature of disease progression and develop a more accurate metabolome-based method for diagnosis of disease progression ultimately giving a better basis for treatment decisions.

Methods: In this study, we used the combination of transient elastography and serum metabolomics of 307 serum samples from a group of 90 patients with CHB before and under treatment (with a follow-up time up to 10 years) at different progression stages over the clinical phases and 43 healthy controls..

Results: Our data show that the metabolomics approach can successfully discover CHB changing from the immune tolerance to the immune clearance phase and show distinctive metabolomes from different medical treatment stages. Perturbations in ammonia detoxification, glutamine and glutamate metabolism, methionine metabolism, dysregulation of branched-chain amino acids, and the tricarboxylic acid (TCA) cycle are the main factors involved in the progression of the disease. Fluctuations increasing in aspartate, glutamate, glutamine, methionine and 13 other metabolites are fingerprints of progression.

Conclusions: The metabolomics approach may expand the diagnostic armamentarium for patients with CHB. This method can provide a more detailed decision basis for starting medical treatment.

Keywords: Biomarker; Chronic hepatitis B; FibroScan; Liver fibrosis; Metabolomics; NMR.

StephenW

慢性乙型肝炎进展的代谢指纹图谱：代谢组的变化和新的诊断可能性
Hien Thi Thu Nguyen 1，Reinhard Wimmer 2，Vang Quy Le 3，Henrik Bygum Krarup 4 5 6
隶属关系
隶属关系

    1个
    奥尔堡大学医院分子诊断学系，丹麦奥尔堡9000 Reberbansgade 15。
    2
    丹麦奥尔堡奥尔堡大学化学与生物科学系。
    3
    丹麦奥尔堡奥尔堡大学CLAAUDIA。
    4
    奥尔堡大学医院分子诊断学系，丹麦奥尔堡9000 Reberbansgade 15。 [email protected]。
    5
    丹麦奥尔堡奥尔堡大学医院消化内科。 [email protected]。
    6
    丹麦奥尔堡奥尔堡大学临床研究所。 [email protected]。

    PMID：33495863 DOI：10.1007 / s11306-020-01767-y

抽象

简介：慢性乙型肝炎（CHB）影响全球2.57亿人，年估计死亡率为880,000人。准确诊断疾病的阶段非常困难，并且有关何时应该开始治疗的最佳时间点存在很大的不确定性。

目的：通过分析和比较CHB不同阶段患者的代谢组并将其与健康个体进行比较，我们希望确定疾病进展的代谢特征，并开发出更准确的基于代谢组学的方法来诊断疾病进展，从而最终提供更好的治疗决策的依据。

方法：在这项研究中，我们采用瞬态弹性成像和血清代谢组学方法，对90例CHB患者在治疗前后（随访时间长达10年）在不同进展阶段的307份血清样本进行了组合。临床阶段和43个健康对照。

结果：我们的数据表明，代谢组学方法可以成功发现CHB从免疫耐受到免疫清除阶段的变化，并显示来自不同治疗阶段的独特代谢组。氨解毒，谷氨酰胺和谷氨酸代谢，蛋氨酸代谢，支链氨基酸失调和三羧酸（TCA）循环紊乱是疾病进展的主要因素。天冬氨酸，谷氨酸，谷氨酰胺，蛋氨酸和其他13种代谢产物的波动增加是进展的指纹。

结论：代谢组学方法可能会扩展CHB患者的诊断装备。该方法可以为开始治疗提供更详细的决策依据。

关键词：生物标志物；慢性乙型肝炎；纤维扫描肝纤维化；代谢组学核磁共振。