Kronsten Victoria Tatiana, Argemi Josepmaria, Kurt Ada Sera, Mannakat Vijay Godhev, Ryan Jennifer Marie, Bataller Ramón, Shawcross Debbie Lindsay
Institute of Liver Studies, Department of Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, UK.
Division of Gastroenterology, Hepatology and Nutrition, Pittsburgh Liver Research Center, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Liver Res. 2022 Feb 3;6(1):21-29. doi: 10.1016/j.livres.2022.01.003. eCollection 2022 Mar.
Severe alcoholic hepatitis (SAH), the most florid form of alcohol-related liver disease (ALD), has a mortality rate of 16% at 28 days. The angiopoietin-Tie 2 system regulates angiogenesis and inflammation, both of which are implicated in the pathogenesis of ALD. This study examined plasma and hepatic gene expression of angiopoietin 1 (ANG1) and angiopoietin 2 (ANG2) in patients with SAH and ALD and investigated their roles as prognostic biomarkers.
A case-control study was performed measuring plasma levels of ANG1 and ANG2 by enzyme-linked immunosorbent assay (ELISA) from 30 patients with SAH (Maddrey's discriminant function ≥32), 32 patients with ALD cirrhosis and 15 healthy controls (HC). RNA sequencing for , , (codes for Tie1 receptor) and (codes for Tie2 receptor) gene expression from a separate cohort study of 79 patients was also performed.
Plasma levels of ANG1 were lower ( = 0.010) and ANG2 were higher ( < 0.0001) in patients with ALD/SAH compared to HC. The ANG2: ANG1 ratio was higher in those with ALD/SAH compared to HC ( < 0.0001). ANG2 levels were the highest in patients who developed sepsis ( = 0.030) and those dying within 90 days ( = 0.020). ANG2 levels correlated positively with model for end-stage liver disease (MELD) score (r = 0.30, = 0.020), Child-Pugh score (r = 0.38, = 0.003), international normalized ratio (r = 0.41, = 0.001) and white blood cell count (r = 0.28, = 0.040) and inversely correlated with albumin (r = -0.26, = 0.040). gene expression from liver biopsies was higher in SAH than that in HC ( < 0.0001), and greater in severe disease ( < 0.0001). gene expression trended towards being lower in SAH than that in HC ( = 0.070) though was upregulated in severe disease ( = 0.0003).
Plasma ANG2 is raised in SAH and ALD and could be useful as a prognostic biomarker in this patient population.
严重酒精性肝炎（SAH）是酒精性肝病（ALD）最严重的形式，28天死亡率为16%。血管生成素-Tie 2系统调节血管生成和炎症，二者均与ALD的发病机制有关。本研究检测了SAH和ALD患者血浆及肝脏中血管生成素1（ANG1）和血管生成素2（ANG2）的基因表达，并探讨它们作为预后生物标志物的作用。
进行了一项病例对照研究，通过酶联免疫吸附测定（ELISA）测量30例SAH患者（Maddrey判别函数≥32）、32例ALD肝硬化患者和15名健康对照（HC）的血浆ANG1和ANG2水平。还对另一项79例患者的队列研究进行了 、 （Tie1受体编码基因）和 （Tie2受体编码基因）基因表达的RNA测序。
与HC相比，ALD/SAH患者的血浆ANG1水平较低（ = 0.010），ANG2水平较高（ < 0.0001）。与HC相比，ALD/SAH患者的ANG2:ANG1比值更高（ < 0.0001）。发生脓毒症的患者（ = 0.030）和90天内死亡的患者（ = 0.020）的ANG2水平最高。ANG2水平与终末期肝病模型（MELD）评分呈正相关（r = 0.30， = 0.020）、Child-Pugh评分呈正相关（r = 0.38， = 0.003）、国际标准化比值呈正相关（r = 0.41， = 0.001）和白细胞计数呈正相关（r = 0.28， = 0.040），与白蛋白呈负相关（r = -0.26， = 0.040）。SAH患者肝活检的 基因表达高于HC（ < 0.0001），在严重疾病中更高（ < 0.0001）。SAH患者肝活检的 基因表达虽低于HC（ = 0.070），但在严重疾病中上调（ = 0.0003）。
SAH和ALD患者血浆ANG2升高，可作为该患者群体的预后生物标志物。
