Department of Molecular Diagnostics, Aalborg University Hospital, Reberbansgade 15, 9000, Aalborg, Denmark.
Department of Chemistry and Bioscience, Aalborg University, Aalborg, Denmark.
Metabolomics. 2021 Jan 25;17(2):16. doi: 10.1007/s11306-020-01767-y.
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.
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.
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..
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.
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.
慢性乙型肝炎（CHB）影响全球 2.57 亿人，年估计死亡率为 88 万人。疾病阶段的准确诊断较为困难，何时开始治疗的最佳时机存在相当大的不确定性。
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，并开发一种更准确的基于代谢组的疾病进展诊断方法，最终为治疗决策提供更好的依据。
在这项研究中，我们使用瞬时弹性成像和血清代谢组学的组合，对 90 名 CHB 患者的 307 份血清样本进行分析，这些患者在不同进展阶段的临床阶段之前和治疗期间（随访时间长达 10 年），并与 43 名健康对照者进行比较。
我们的数据表明，代谢组学方法可以成功地发现从免疫耐受到免疫清除阶段的 CHB 变化，并显示出与不同治疗阶段的不同代谢组学特征。氨解毒、谷氨酰胺和谷氨酸代谢、蛋氨酸代谢、支链氨基酸失调以及三羧酸（TCA）循环的失调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 种代谢物的波动增加是进展的特征指纹。
代谢组学方法可能会扩展 CHB 患者的诊断工具。这种方法可以为开始治疗提供更详细的决策依据。
