门静脉高压症是慢性肝病患者进展至肝硬化阶段的常见并发症，患者往往存在消化道静脉曲张破裂出血风险，所以控制好门静脉压力，预防出血非常关键。

 

第29届亚太肝病学会年会（APASL2020）召开期间，美国耶鲁大学Guadalupe Garcia Tsao教授应大会邀请，介绍了门静脉高压症治疗的最前沿进展，包括目前在研、指南尚未纳入的策略。

 

Guadalupe Garcia-Tsao教授所在团队是全球门静脉高压临床实践和学术研究的发源地之一，是全球门静脉高压领域发展的代表之一。《国际肝病》前方记者有幸采访到Garcia-Tsao教授，访谈内容记录如下，供读者参考。

 

Guadalupe Garcia-Tsao

 

美国耶鲁大学

 

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1β-受体阻滞剂：治疗门静脉高压症的最重要药物

 

β-受体阻滞剂可能是目前用于治疗门静脉高压症的最重要药物。最近的研究表明，代偿期肝硬化患者应用β-受体阻滞剂治疗，确实可以预防失代偿和静脉曲张出血的发生，而且可以预防最常见并发症——腹水的发生。

 

对于高风险的静脉曲张患者，β-受体阻滞剂已被证明可以降低首次静脉曲张出血的发生率，并且由于β-受体阻滞剂是通过降低门静脉压力，作用于门静脉高压症的病理生理学，因此，和作为局部治疗的曲张静脉套扎相比，β-受体阻滞剂是更为合理的治疗方法。

 

对于已经发生出血的患者，一旦出血缓解，并且在曲张静脉急性出血期间没有应用经颈静脉肝内门体分流术（TIPS）治疗，β-受体阻滞剂是联合治疗以预防再次出血的关键组分。

 

β-受体阻滞剂治疗门静脉高压症的适应证为：无或有静脉曲张以及曾经发生过静脉曲张出血的代偿期或失代偿期肝硬化患者。

 

β-受体阻滞剂治疗的禁忌证为：患者服用β-受体阻滞剂时发生低血压、哮喘患者（β-受体阻滞剂会加重病情），或者患者的心率较慢（应用β-受体阻滞剂时，会导致晕厥或其他心血管症状）。

 

原文呈现：

 

<Hepatology Digest>: What are the main indications and contraindications of non-selective beta-blockers in patients with cirrhosis?

 

Dr Garcia-Tsao: Beta-blockers are perhaps the most important medication that we have for portal hypertension at this time. In the patient who has compensated cirrhosis, it has recently been shown that beta-blockers can actually prevent decompensation and variceal hemorrhage, as well as ascites, the most common complicating event. Where there are high-risk varices, beta-blockers have been shown to decrease the rate of first variceal hemorrhage, and because they act on the pathophysiology of portal hypertension by reducing portal pressure, they are a much more rational therapy than ligating those varices as a local therapy, for example. In the setting of a patient who has bled, once bleeding has resolved and TIPs was not used during the acute variceal hemorrhage, beta-blockers are the key component of combination therapy to prevent repeat bleeding episodes. The indications are: any patient with cirrhosis, compensated or decompensated; with or without varices; and patients who have bled from varices. The contraindications are where a patient gets hypotensive on the beta-blocker. Also where a patient has asthma (exacerbated by beta-blockers), and patients already with a low heart rate (resulting in syncope or other cardiovascular symptoms in the presence of beta-blockers).

 

他汀类药物：失代偿肝硬化患者需慎用

 

他汀类药物与β-受体阻滞剂通常作用于不同的层面：β-受体阻滞剂是通过减少血流发挥作用，而他汀类药物是通过降低肝内阻力发挥作用，因此，由于二者作用于不同的层面，应用他汀类药物+β-受体阻滞剂联合治疗，具有累积效应。

 

代偿期患者应用他汀类药物的安全性良好，不会导致肝毒性。实际上，对于非酒精性脂肪性肝炎（NASH）患者，通过应用他汀类药物控制高脂血症，可以改善转氨酶水平。

 

然而，对于黄疸或失代偿患者，每日应用40 mg或更高剂量的辛伐他汀治疗，与横纹肌溶解显著相关，这种情况并非真正的肝毒性，而是骨骼肌的损伤，这些患者会因为横纹肌溶解而引起肾功能衰竭。因此，对这些患者必须加以谨慎。

 

所以，需要等待临床试验的结果，以确定哪些肝硬化患者适合应用他汀类药物治疗。

 

原文呈现：

 

<Hepatology Digest>: In your presentation, you raised the topic of statins in portal hypertension, and suggested they should be used with caution. Can you talk about that?

 

Dr Garcia-Tsao: In general, statins act on a separate plane to beta-blockers. Beta-blockers act by decreasing flow. Statins act by decreasing intrahepatic recesses. Therefore the use of statins plus beta-blockers has a cumulative effect because they act at different levels. Statins in the compensated patient are safe; they do not produce hepatotoxicity. In fact, in patients with NASH, by controlling hyperlipidemia, they improve aminotransferase levels. However, in jaundiced or decompensated patients, doses of 40mg or more of simvastatin have been associated with significant rhabdomyolysis. It is not really hepatotoxicity, but causing damage to muscle. So these patients can get into trouble with kidney failure from the rhabdomyolysis. We have to be cautious in these patients, and we need to wait for the outcomes of trials to see which groups of patients with cirrhosis are going to be candidates for statins.