J Hepatol:NSBB治疗降低肝硬化患者肠粘膜通透性

2013-05-06 陈郁婷 互联网

肝硬化患者由于身体防御机制的异常,因而比普通人更容易发生细菌感染。然而,目前肝硬化并发细菌感染(如自发性细菌性腹膜炎)患者的预后效果并不理想,因此,探索导致肠粘膜通透性异常以及与细菌移位相关的机制或许能够促进新治疗策略的开发。针对上述情况,来自奥地利维也纳医科大学内科医学第三部门肠胃肝脏科的Thomas Reiberger博士等人进行一项研究,研究结果在线发表在2012年12月20日的《肝脏病学杂

肝硬化患者由于身体防御机制的异常,因而比普通人更容易发生细菌感染。然而,目前肝硬化并发细菌感染(如自发性细菌性腹膜炎)患者的预后效果并不理想,因此,探索导致肠粘膜通透性异常以及与细菌移位相关的机制或许能够促进新治疗策略的开发。针对上述情况,来自奥地利维也纳医科大学内科医学第三部门肠胃肝脏科的Thomas Reiberger博士等人进行一项研究,研究结果在线发表在2012年12月20日的《肝脏病学杂志》(Journal of Hepatology)上。作者发现,非选择性beta受体阻滞剂(NSBB)治疗能改善肝硬化患者胃十二指肠/肠粘膜通透性以及减少细菌移位。

该研究的目的是评估肝硬化合并门静脉高压症(PHT)患者使用NSBB治疗前后的胃肠道渗透率和细菌移位的变化,一共纳入了50例肝硬化患者进行研究。研究人员测量了NSBB治疗前和治疗时的肝静脉压力梯度(HVPG)。使用蔗糖-果糖-甘露醇(SLM)法测定胃十二指肠和肠粘膜的通透性。并检测了抗麦胶蛋白(anti-gliadin)抗体和抗肌内膜(anti-endomysial)抗体的水平。使用ELISA法定量测定了细菌脂多糖(LPS)结合蛋白(LBP)和白介素-6(IL-6)的水平,同时对NOD2和toll样受体(LTR2)的多态性进行基因分型。

研究结果如下,纳入的50例患者中,72%为男性,18%腹水感染,60%病因为酗酒。胃十二指肠和肠粘膜通透性异常的患者分别占总数的72%和59%。与HVPG小于20mmHg的患者相比,严重门静脉高压症患者(HVPG大于或等于20mmHg,n=35)胃十二指肠炎/肠粘膜通透性标记增加(尿液蔗糖水平p=0.049,蔗糖/甘露糖比值p=0.007,肠粘膜通透性指数p=0.002),细菌移位也增加(LBP p=0.002,IL-6 p=0.025)。绝大部分患者抗麦胶蛋白抗体水平升高(IgA:60%,IgG:34%),然而没有检测到抗肌内膜抗体。门静脉压(即HVPG)与胃十二指肠炎/肠粘膜通透性的所有标记,以及与LBP和IL-6的水平显着相关。NOD2和LTR2基因风险变异与肠粘膜通透性的异常和细菌移位标记的增高存在相关关系。根据NSBB治疗期间HVPG的随访数据,研究人员发现胃十二指肠炎/肠粘膜通透性得到改善,细菌移位水平降低(LBP -16% p=0.018,IL-6 -41% p<0.0001)而且不仅仅局限于血液动力学响应。在随访期间,发现SLM结果异常以及高LBP/IL-6水平与静脉曲张出血风险的增加相关,但与死亡率无关。

肝硬化患者常出现胃十二指肠炎/肠粘膜通透性、抗麦胶蛋白抗体水平以及细菌移位的异常,而且这三者与门静脉高压症的程度相关。肠粘膜通透性及细菌移位的增加,是导致肝硬化合并门静脉高压症患者严重感染的复发以及发生其他并发症重要机制。本研究发现,使用NSBB治疗能改善胃十二指肠炎/肠粘膜通透性、减少细菌移位,此效应部分独立于它们(NSBB)对于门静脉压的血液动力学效应,上述作用可能有助于降低静脉曲张出血的风险。

肝硬化相关的拓展阅读:

Non-selective betablocker therapy decreases intestinal permeability and serum levels of LBP and IL-6 in patients with cirrhosis.
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.
METHODS
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.
RESULTS
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 ⩾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 bacterial translocation (LBP p=0.002; IL-6 p=0.025) than patients with HVPG <20mmHg. 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.
CONCLUSIONS
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.

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    2014-04-05 zhmscau
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    2013-07-16 hb2008ye
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    2013-05-08 gwc384
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    2013-05-08 HNYYM