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在2013年欧洲肝病学会(European Association for the Study of the Liver,EASL)主办的国际肝病大会(the International Liver Congress,ILC)上,奥地利维也纳医科大学报告了一项新的临床研究数据,研究发现,非选择性β受体阻滞剂(NSBB)能有效改善肝硬化患者的胃/肠通透性,减少细菌移位,有助于降低食管静脉曲张破裂出血的风险。
研究人员纳入50例肝硬化患者,在NSBB治疗前和治疗当中进行以下测量:
1、肝静脉压力梯度(HVPG)评估门静脉压力
2、蔗糖乳果糖甘露醇(SLM)测试胃和肠道通透性
3、脂多糖结合蛋白(LBP)和白细胞介素-6的水平(IL-6)的定量检测。随访期间记录出血率和死亡率。
研究结果如下:病人的特点:72%男性,18%有腹水,60%为酒精性病因。NSBB治疗之前,分别在72%和59%的患者中发现胃和肠道通透性异常。相对与HVPG<20mmHg患者,重度门静脉高压症患者(HVPG≥20mmHg;n=35)胃/肠通透性(尿蔗糖水平,P=0.049;蔗糖或甘露醇比值,P=0.007;肠道通透性指数,p=0.002),以及细菌移位(LBP,P=0.002;IL-6,P=0.025)标志物增加。NSBB治疗不仅导致HVPG显着减少,而且改善了胃/肠通透性,减少了细菌移位(LBP−16%,P = 0.018;IL-6−41%,P<0.0001)。
胃和肠道通透性异常在肝硬化患者很常见,与门脉高压的程度相关。该研究为肝硬化患者应用非选择性β受体阻滞剂治疗提供一个新的理论基础。
论文摘要:
Improvement of intestinal permeability and reducing bacterial translocation by betablocker treatment is associated with a lower risk of variceal bleeding
Introduction: Evaluation of gastrointestinal permeability and bacterial translocation in cirrhotic patients with portal hypertension (PHT) prior and after nonselective betablocker (NSBB) treatment.
Methods: 50 cirrhotic patients underwent the following measurements prior and under NSBB treatment:
i. portal pressure was assessed by the hepatic venous pressure gradient (HVPG),
ii. gastroduodenal and intestinal permeability was evaluated by the sucrose-lactulose-mannitol (SLM) test, and
iii. levels of LPS-binding protein (LBP) and interleukin-6 (IL-6) were quantified by ELISA. Bleeding rates and mortality were recorded during follow-up by clinical visits.
Results: Patient characteristics: 72% male, 18% ascites, 60% alcoholic etiology). Prior to NSBB treatment, abnormal gastroduodenal and intestinal permeability were found in 72% and 59% of patients, respectively. Patients with severe portal hypertension (HVPG ≥20mmHg;n= 35) had increased markers of gastroduodenal/intestinal permeability (urine sucrose levels p = 0.049; sucrose/mannitol ratios p = 0.007; intestinal permeability indices p = 0.002), and of bacterial translocation (LBP p = 0.002; IL-6 p = 0.025) than patients with HVPG <20mmHg. NSBB treatment
did not only result in a significant reduction in HVPG, but also in improvement of gastroduodenal/intestinal permeability and a decrease of bacterial translocation (LBP −16% p = 0.018; IL-6−41% p < 0.0001) levels These improvements were not limited to hemodynamic responders. Patients with abnormal results by the SLM test indicating abnormal gastroduodenal (p = 0.066) or intestinal permeability (p = 0.084) had a clear trend towards a higher incidence of variceal bleeding. Accordingly, patients with high LBP (p = 0.180) and/or IL-6 (p = 0.038) levels were also at increased risk of variceal bleeding during follow-up. However, these findings did not translate into an increased mortality in patients with abnormal gastroduodenal (p = 0.870) or intestinal permeability (p = 0.994), nor in patients with high levels of LBP (p = 0.571) and
IL-6 (p = 0.594).
Conclusions: Abnormal gastroduodenal and intestinal permeability are common findings in cirrhotic patients and are correlated with the degree of portal hypertension. NSBB treatment ameliorates gastroduodenal/intestinal permeability and reduces bacterial translocation, which may contribute to the reduced risk of variceal bleeding observed under NSBB treatment. |
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