Div. of Gastroenterology & Hepatology, Dept. of Internal Medicine III, Medical University of Vienna, Austria.
J Hepatol. 2013 May;58(5):911-21. doi: 10.1016/j.jhep.2012.12.011. Epub 2012 Dec 20.
BACKGROUND & AIMS: We evaluated the gastrointestinal permeability and bacterial translocation in cirrhotic patients with portal hypertension (PHT) prior to and after non-selective betablocker (NSBB) treatment.
Hepatic venous pressure gradient (HVPG) was measured prior to and under NSBB treatment. Gastroduodenal and intestinal permeability was assessed by the sucrose-lactulose-mannitol (SLM) test. Anti-gliadin and anti-endomysial antibodies were measured. Levels of LPS-binding protein (LBP) and interleukin-6 (IL-6) were quantified by ELISA, and NOD2 and toll-like receptor 2 (TLR2) polymorphisms were genotyped.
Fifty cirrhotics were included (72% male, 18% ascites, 60% alcoholic etiology). Abnormal gastroduodenal and intestinal permeability was found in 72% and 59% of patients, respectively. Patients with severe portal hypertension (HVPG ≥20 mm Hg; 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 bacterial translocation (LBP p=0.002; IL-6 p=0.025) than patients with HVPG <20 mm Hg. A substantial portion of patients showed elevated levels of anti-gliadin antibodies (IgA: 60%, IgG: 34%) whereas no anti-endomysial antibodies were detected. A significant correlation of portal pressure (i.e., HVPG) with all markers of gastroduodenal/intestinal permeability and with LBP and IL-6 levels was observed. NOD2 and TLR2 risk variants were associated with abnormal intestinal permeability and elevated markers of bacterial translocation. At follow-up HVPG measurements under NSBB, we found an amelioration of gastroduodenal/intestinal permeability and a decrease of bacterial translocation (LBP - 16% p=0.018; IL-6 - 41% p<0.0001) levels, which was not limited to hemodynamic responders. Abnormal SLM test results and higher LBP/IL-6 levels were associated with a higher risk of variceal bleeding during follow-up but not with mortality.
Abnormal gastroduodenal/intestinal permeability, anti-gliadin antibodies, and bacterial translocation 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 partially independent of their hemodynamic effects on portal pressure, which may contribute to a reduced risk of variceal bleeding.
我们评估了门脉高压症（PHT）患者在非选择性β受体阻滞剂（NSBB）治疗前后的胃肠通透性和细菌易位。
在 NSBB 治疗前后测量肝静脉压力梯度（HVPG）。通过蔗糖-乳果糖-甘露醇（SLM）试验评估胃十二指肠和肠道通透性。测量抗麦胶蛋白和抗内肌层抗体。通过 ELISA 定量 LPS 结合蛋白（LBP）和白细胞介素 6（IL-6）的水平，并对 NOD2 和 Toll 样受体 2（TLR2）多态性进行基因分型。
共纳入 50 例肝硬化患者（72%为男性，18%为腹水，60%为酒精性病因）。分别有 72%和 59%的患者存在胃十二指肠和肠道通透性异常。HVPG≥20mmHg 的严重门静脉高压症患者（n=35）具有更高的胃十二指肠/肠道通透性标志物（尿蔗糖水平 p=0.049；蔗糖/甘露醇比值 p=0.007；肠道通透性指数 p=0.002）和细菌易位（LBP p=0.002；IL-6 p=0.025），而 HVPG<20mmHg 的患者则没有。大量患者表现出抗麦胶蛋白抗体升高（IgA：60%，IgG：34%），但未检测到抗内肌层抗体。门脉压（即 HVPG）与胃十二指肠/肠道通透性以及 LBP 和 IL-6 水平的所有标志物均呈显著相关。NOD2 和 TLR2 风险变异与肠道通透性异常和细菌易位标志物升高有关。在 NSBB 下的后续 HVPG 测量中，我们发现胃十二指肠/肠道通透性和细菌易位（LBP-16%，p=0.018；IL-6-41%，p<0.0001）水平有所改善，且这种改善不局限于血流动力学反应者。异常的 SLM 试验结果和较高的 LBP/IL-6 水平与随访期间静脉曲张出血风险增加相关，但与死亡率无关。
胃十二指肠/肠道通透性异常、抗麦胶蛋白抗体和细菌易位是肝硬化患者的常见发现，与门静脉高压程度相关。NSBB 治疗可改善胃十二指肠/肠道通透性并减少细菌易位，部分独立于其对门静脉压力的血流动力学效应，这可能有助于降低静脉曲张出血的风险。
