Lashen Sameh A, Shamseya Mohammed M, Madkour Marwa A, Abdel Salam Radwa M, Mostafa Sanaa S
Division of Hepatology and Gastroenterology, Faculty of Medicine, Alexandria University, Alexandria 21521, Egypt.
Department of Experimental and Clinical Internal Medicine, Medical Research Institute, Alexandria 21561, Egypt.
World J Hepatol. 2022 Feb 27;14(2):429-441. doi: 10.4254/wjh.v14.i2.429.
Portal hypertension, a common complication associated with liver cirrhosis, can result in variceal bleeding, which greatly impacts patient survival. Recently, β-arrestin-2 has been shown to predict the acute hemodynamic response to nonselective β-blocker therapy for cirrhotic portal hypertension. However, more data is needed on the long-term effects of and changes in β-arrestin-2 following nonselective β-blocker therapy.
To investigate the expression and role of β-Arrestin-2 in predicting the long-term response to nonselective β-blockers in cirrhotic portal hypertensive patients.
We prospectively enrolled 91 treatment-naïve patients with cirrhotic portal hypertension. Baseline clinical and laboratory data were obtained. Gastroscopy was performed for grading and treating varices and obtaining gastric antral biopsies. We measured the serum and antral expression of β-arrestin-2 and obtained Doppler measurement of the portal vein congestion index. Treatment with nonselective β-blockers was then started. The patients were followed up for 18 mo, after which they have undergone a repeat antral biopsy and re-evaluation of the portal vein congestion index.
A higher serum level and antral expression of β-arrestin-2 was associated with longer bleeding-free intervals, greater reduction in the portal vein congestion index, and improved grade of varices. Among patients with a low β-arrestin-2 expression, 17.6% were nonselective β-blocker responders, whereas, among those with high expression, 95.1% were responders ( < 0.001). A serum β-arrestin-2 value ≥ 2.23 ng/mL was associated with a lower likelihood of variceal bleeding (90% sensitivity and 71% specificity). β-arrestin-2 expression significantly decreased after nonselective β-blocker therapy.
β-arrestin-2 expression in cirrhotic portal hypertension predicts the clinical response to long-term nonselective β-blocker treatment. Serum β-arrestin-2 is a potential noninvasive biomarker for selecting the candidate patients for nonselective β-blockers.
门静脉高压是肝硬化常见的并发症,可导致静脉曲张破裂出血,严重影响患者生存。最近研究表明,β-抑制蛋白2可预测肝硬化门静脉高压患者对非选择性β受体阻滞剂治疗的急性血流动力学反应。然而,关于非选择性β受体阻滞剂治疗后β-抑制蛋白2的长期影响和变化,仍需要更多数据。
研究β-抑制蛋白2在预测肝硬化门静脉高压患者对非选择性β受体阻滞剂长期反应中的表达及作用。
前瞻性纳入91例未经治疗的肝硬化门静脉高压患者。收集基线临床和实验室数据。进行胃镜检查以对静脉曲张进行分级和治疗,并获取胃窦活检样本。检测血清和胃窦组织中β-抑制蛋白2的表达,并通过多普勒测量门静脉充血指数。随后开始使用非选择性β受体阻滞剂进行治疗。对患者进行18个月的随访,之后再次进行胃窦活检并重新评估门静脉充血指数。
血清β-抑制蛋白2水平升高及胃窦组织中β-抑制蛋白2表达增加与无出血间隔时间延长、门静脉充血指数降低幅度更大以及静脉曲张分级改善相关。在β-抑制蛋白2低表达的患者中,17.6%为非选择性β受体阻滞剂反应者,而在高表达患者中,95.1%为反应者(P<0.001)。血清β-抑制蛋白2值≥2.23 ng/mL与静脉曲张出血可能性较低相关(敏感性为90%,特异性为71%)。非选择性β受体阻滞剂治疗后β-抑制蛋白2表达显著降低。
肝硬化门静脉高压患者中β-抑制蛋白2的表达可预测长期非选择性β受体阻滞剂治疗的临床反应。血清β-抑制蛋白2是选择非选择性β受体阻滞剂候选患者的潜在无创生物标志物。