血管收縮素轉換酶抑制劑與血管收縮素受體阻斷劑可否在肝硬化患者使用？

Clinical Use of Angiotensin Converting Enzyme and Angiotensin Receptor Blocker in Patients with Liver Cirrhosis

許偉帆(Wei-Fan Hsu) ； 鍾承軒(Chen-Shuan Chung) ； 彭渝森(Yu-Sen Peng) ； 梁程超(Cheng-Chao Liang)

《內科學誌》 25卷2期 (2014/04) Pp. 94-100

https://doi.org/10.6314/JIMT.2014.25(2).06

摘要

肝硬化導致的肝臟門靜脈高壓是肝硬化主要的併發症，而且門脈高壓與肝硬化患者預後息息相關。乙型接受體阻斷劑（β-blockers, BB）透過降低心臟輸出量與內臟血流量達到降低門脈高壓的目的，但是約15%的患者使用BB會出現不能耐受的副作用，同時不到40%的患者可以達到治療目標（肝靜脈壓力梯度小於12 mmHg或從基礎值下降20%），因此有許多學者尋找替代的治療。隨著基礎研究的發展，有學者認為腎素－血管收縮素－醛固酮系統是個可能的治療標的。雖然不同的臨床研究結果顯示血管收縮素轉換酶抑制劑（angiotensin converting enzyme inhibitor, ACEi）與血管收縮素受體阻斷劑（angiotensin receptor blocker, ARB）可能會降低門脈高壓卻也可能帶來體循環低血壓、腎功能異常的副作用。2001年Gonzalez-Abraldes與Schepke等人的隨機分配臨床研究顯示ARB不能降低或是只有中度地降低門脈高壓，卻有明顯的體循環低血壓與腎功能異常的副作用，一個可能改善肝硬化門脈高壓的希望卻轉變成惡化肝硬化患者腎功能與血壓的夢魘。2012年美國肝臟研究協會的臨床指引提到在肝硬化腹水的患者使用ACEi與ARB可能導致傷害，同時2010年歐洲肝臟研究協會的臨床指引指出不應該在有（肝硬化）腹水的患者使用這兩類藥物。臨床醫師在肝硬化患者使用ACEi與ARB時須特別注意患者的血壓與腎功能的變化。

關鍵字

血管收縮素轉換酶抑制劑（Angiotensin converting enzyme inhibitor） ； 血管收縮素受體阻斷劑（Angiotensin receptor blocker） ； 肝硬化（Liver cirrhosis） ； 門脈高壓（Portal hypertension）

並列摘要

Portal hypertension is a major complication of liver cirrhosis and is associated with increased mortality. Beta-blocker can reduce portal pressure by lowering cardic output and splanchnic blood flow. However, about 15% of patients are unable to tolerate beta-blocker and less than 40% of patients can achieve an optiaml response (hepatic venous pressure gradient less than 12 mmHg or more than 20% decreased from baseline). Therefore, many researchers try to find an alternative treatment. Renin-angiotension -aldosterone may be an alternative therapuetic target in patients with liver cirrhosis. Although different clinical trials showed angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) may decrease portal pressure, these two kinds of medications may worse systemic blood pressure and renal function. In 2001, randomized controlled trials from Gonzalez-Abraldes et al. and Schepke et al. showed ARBs has no or moderately decrease in portal pressure with adverse effects of arterial hypotension and renal impairment. As Dr. Sanayl comments in the article ＂Angiotensin Receptor Blockade and Portal Hypertension: Paradise Gained and Paradise Lost.＂ suggested ARBs should not be used in routine clinical practice in patients with liver cirrhosis. Guildlines of American Association for the Study of Liver Disease mentioned that ＂use of ACEi and ARB in patients with liver cirrhosis and ascites may be harmfaul.＂ Guildlines of European Association for the Study of the Live pointed ＂they (ACEi and ARB) should generally not be used in patients with ascites.＂ Doctors should use ACEi and ARB carefully in patients with liver cirrhosis and monitor blood pressure and renal function, especially in patient with liver cirrhosis and ascites or advanced cirrhosis.