肝细胞衍生的外泌体可能作为急性肝衰竭患者肝再生和预后评估的生物标志物。
Hepatocyte-derived exosome may be as a biomarker of liver regeneration and prognostic valuation in patients with acute-on-chronic liver failure.
机构信息
Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China.
Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer, Beijing, 100069, China.
出版信息
Hepatol Int. 2021 Aug;15(4):957-969. doi: 10.1007/s12072-021-10217-3. Epub 2021 Jul 7.
BACKGROUND
The assessment of liver regeneration is particularly critical for patients with acute-on-chronic liver failure (ACLF). Exosome has both the advantages of specificity of liver biopsy and noninvasion of peripheral blood, which may be the potential biomarker of liver disease.
METHODS
The patients with chronic hepatitis B (CHB) and ACLF were enrolled from outpatients and inpatients in Beijing Youan Hospital, Capital Medical University. The exosomes in plasma were extracted by ultracentrifuge using Optima XPN-100 Ultracentrifuge. Exosomes were dyed with fluorescent direct-labeled antibody and the expression profile was assayed using ImageStream® X MKII Imaging Flow Cytometer.
RESULTS
The percentage of exosomes with ALB and CD63 was significant higher in ACLF than that in CHB. The percentage of exosomes with ALB and CD63 and VEGF increased in CHB, but decreased in ACLF. The exosomes with ALB, CD63, and VEGF were significant more in survival group than that in dead group in patients with ACLF. The sensitivity and specificity of exosomes with CD63, ALB, and VEGF were significantly higher than the other markers of liver regeneration and prognostic valuation in patients with ACLF including AFP. The hepatocyte-derived exosomes expression profile had no difference in different stages and different AFP levels of patients with ACLF.
CONCLUSION
The exosomes profile with ALB and VEGF may be a more accurate and specific biomarker of liver regeneration and prognostic valuation than AFP in patients with ACLF. In addition, the exosomes profile with CD63 and ALB may be an early-warning marker in patients with ACLF.
背景
肝再生的评估对慢加急性肝衰竭（ACLF）患者尤为关键。外泌体兼具肝活检的特异性和外周血非侵入性的优点，可能是肝病的潜在生物标志物。
方法
本研究纳入了首都医科大学附属北京佑安医院的门诊和住院慢性乙型肝炎（CHB）和 ACLF 患者。使用 Optima XPN-100 超速离心机从血浆中提取外泌体。使用荧光直接标记抗体对外泌体进行染色，并使用 ImageStream® X MKII 成像流式细胞仪检测其表达谱。
结果
ALB 和 CD63 阳性的外泌体在 ACLF 患者中的百分比明显高于 CHB 患者。ALB 和 CD63 阳性以及 VEGF 阳性的外泌体在 CHB 患者中增加，但在 ACLF 患者中减少。在 ACLF 患者中，存活组的 ALB、CD63 和 VEGF 阳性外泌体明显多于死亡组。在 ACLF 患者中，与其他肝再生和预后评估标志物（包括 AFP）相比，CD63、ALB 和 VEGF 阳性外泌体的敏感性和特异性显著更高。ALB 和 VEGF 阳性的外泌体表达谱在不同阶段和不同 AFP 水平的 ACLF 患者中没有差异。
结论
与 AFP 相比，ALB 和 VEGF 阳性的外泌体特征可能是 ACLF 患者肝再生和预后评估更准确、更特异的生物标志物。此外，CD63 和 ALB 阳性的外泌体可能是 ACLF 患者的早期预警标志物。
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