Lin Caorui, Huang Ying, Luo Linjie, Fang Fengling, Zhang Jiawei, Xun Zhen, Fu Ya, Shang Hongyan, Liu Can, Ou Qishui
Department of Laboratory Medicine, Gene Diagnosis Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Front Immunol. 2022 Jul 1;13:927761. doi: 10.3389/fimmu.2022.927761. eCollection 2022.
The need to be diagnosed with liver biopsy makes the clinical progression of chronic HBV infection diagnosis a challenge. Existing HBV serum biochemical assays are used throughout clinical but have limited effects. Studies have shown that mitochondrial function is tightly coupled to HBV infection. Here, we verified the diagnostic value of serum Adenosine Triphosphate (ATP) as a potential marker for differential HBV infection progress by detecting the level of ATP in the serum from a wide spectrum of HBV-infected populations, and confirmed the role of ATP in the deterioration of HBV infection-related diseases through HBV-infected cells and mouse models. The results showed that there were significantly lower serum ATP levels in HBeAg-positive CHB patients compared with healthy controls. And during the progression of CHB to liver cirrhosis and hepatocellular carcinoma, the ATP level was increased but not higher than healthy controls. The area under the curve (AUC) of serum ATP was 0.9063 to distinguish HBeAg-positive CHB from healthy, and another AUC was 0.8328 in the CHB against the HCC group. Preliminary exploration of the mechanism indicated that the decline of serum ATP was due to impaired mitochondria in CHB patients. Our data provide evidence that serum ATP distinguishes the various progress of HBV infection-related diseases and expands diagnostic biomarkers for HBeAg-positive CHB patients with healthy controls.
需要通过肝活检进行诊断使得慢性乙型肝炎病毒（HBV）感染的临床进展诊断成为一项挑战。现有的HBV血清生化检测在临床中广泛使用，但效果有限。研究表明，线粒体功能与HBV感染紧密相关。在此，我们通过检测广泛的HBV感染人群血清中的三磷酸腺苷（ATP）水平，验证了血清ATP作为区分HBV感染不同进展的潜在标志物的诊断价值，并通过HBV感染的细胞和小鼠模型证实了ATP在HBV感染相关疾病恶化中的作用。结果显示，与健康对照相比，HBeAg阳性慢性乙型肝炎（CHB）患者的血清ATP水平显著降低。并且在CHB进展为肝硬化和肝细胞癌的过程中，ATP水平升高但不高于健康对照。血清ATP的曲线下面积（AUC）为0.9063，用于区分HBeAg阳性CHB与健康对照，在CHB与肝癌组之间的另一个AUC为0.8328。对机制的初步探索表明，CHB患者血清ATP的下降是由于线粒体受损。我们的数据提供了证据，表明血清ATP可区分HBV感染相关疾病的不同进展，并为HBeAg阳性CHB患者与健康对照扩展了诊断生物标志物。
