Plasma angiopoietin 2 as a novel prognostic biomarker in alcohol-related cirrhosis and hepatitis

Q2 Medicine Liver Research Pub Date : 2022-03-01 DOI:10.1016/j.livres.2022.01.003

Victoria Tatiana Kronsten , Josepmaria Argemi , Ada Sera Kurt , Godhev Mannakat Vijay , Jennifer Marie Ryan , Ramón Bataller , Debbie Lindsay Shawcross

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Abstract

Background and aim

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.

Methods

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 ANG1, ANG2, TIE1 (codes for Tie1 receptor) and TEK (codes for Tie2 receptor) gene expression from a separate cohort study of 79 patients was also performed.

Results

Plasma levels of ANG1 were lower (P = 0.010) and ANG2 were higher (P < 0.0001) in patients with ALD/SAH compared to HC. The ANG2: ANG1 ratio was higher in those with ALD/SAH compared to HC (P < 0.0001). ANG2 levels were the highest in patients who developed sepsis (P = 0.030) and those dying within 90 days (P = 0.020). ANG2 levels correlated positively with model for end-stage liver disease (MELD) score (r = 0.30, P = 0.020), Child-Pugh score (r = 0.38, P = 0.003), international normalized ratio (r = 0.41, P = 0.001) and white blood cell count (r = 0.28, P = 0.040) and inversely correlated with albumin (r = −0.26, P = 0.040).

ANG1 gene expression from liver biopsies was higher in SAH than that in HC (P < 0.0001), and greater in severe disease (P < 0.0001). ANG2 gene expression trended towards being lower in SAH than that in HC (P = 0.070) though was upregulated in severe disease (P = 0.0003).

Conclusions

Plasma ANG2 is raised in SAH and ALD and could be useful as a prognostic biomarker in this patient population.

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血浆血管生成素2作为酒精相关性肝硬化和肝炎新的预后生物标志物

背景和目的重度酒精性肝炎(SAH)是酒精相关肝病(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，这两者都与ALD的发病机制有关。本研究检测了SAH和ALD患者血浆和肝脏中血管生成素1 (ANG1)和血管生成素2 (ANG2)的基因表达，并探讨了它们作为预后生物标志物的作用。方法采用酶联免疫吸附试验(ELISA)检测30例SAH (Maddrey’s判别功能≥32)患者、32例ALD肝硬化患者和15例健康对照(HC)患者血浆中ANG1和ANG2的水平。还对79例患者的单独队列研究中的ANG1、ANG2、TIE1 (TIE1受体编码)和TEK (Tie2受体编码)基因表达进行了RNA测序。结果两组患者血浆ANG1水平较低(P = 0.010)， ANG2水平较高(P <0.0001)，与HC相比，ALD/SAH患者。ALD/SAH患者的ANG2: ANG1比值高于HC (P <0.0001)。脓毒症患者ANG2水平最高(P = 0.030)， 90天内死亡患者ANG2水平最高(P = 0.020)。ANG2水平与终末期肝病模型(MELD)评分(r = 0.30, P = 0.020)、Child-Pugh评分(r = 0.38, P = 0.003)、国际标准化比值(r = 0.41, P = 0.001)、白细胞计数(r = 0.28, P = 0.040)呈正相关，与白蛋白(r = - 0.26, P = 0.040)负相关。肝活检中ANG1基因在SAH中的表达高于HC (P <0.0001)，重症患者更大(P <0.0001)。ANG2基因在SAH中的表达倾向于低于HC (P = 0.070)，但在严重疾病中表达上调(P = 0.0003)。结论血浆ANG2在SAH和ALD患者中升高，可作为该患者的预后生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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