Wang Roy X, Serper Marina, Taddei Tamar H, Kaplan David E, Mahmud Nadim
Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Department of Medicine, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA.
Am J Gastroenterol. 2025 May 1;120(5):1057-1065. doi: 10.14309/ajg.0000000000002976. Epub 2024 Jul 25.
Angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB) may have hepatic benefits in patients with primarily chronic liver disease. ACE-I/ARB have not been evaluated in broad cohorts inclusive of those with decompensated cirrhosis. We analyzed the real-world association between ACE-I/ARB exposure and cirrhosis-related outcomes in a national cohort.
We performed a retrospective, active comparator new user study of patients with cirrhosis in the Veterans Health Administration. We identified new initiators of ACE-I/ARB or calcium channel blockers (comparator). Inverse probability treatment weighting balanced key confounders and Cox regression evaluated the association between ACE-I/ARB and outcomes of mortality, cirrhosis decompensation, and hepatocellular carcinoma (HCC). In exploratory analysis, cause-specific competing risk models evaluated liver-related vs cardiovascular (CV)-related vs nonliver/non-CV-related mortality.
There were 904 ACE-I/ARB and 352 calcium channel blocker new initiators. In inverse probability treatment weighting Cox regression, ACE-I/ARB exposure was associated with reduced mortality (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.61-0.81, P < 0.001). In patients with compensated cirrhosis, ACE-I/ARB were not associated with hepatic decompensation or HCC. Cause-specific hazard models showed ACE-I/ARB exposure was associated with reduction in nonliver/non-CV-related mortality (cause-specific HR 0.49, 95% CI 0.38-0.62, P < 0.001) but not liver-related or CV-related mortality. In Child-Turcotte-Pugh A patients, ACE-I/ARB were associated with decreased CV-related mortality (cause-specific HR 0.41, 95% CI 0.26-0.65, P < 0.001).
ACE-I/ARB exposure was associated with reduced mortality, potentially through CV and other (renal, malignancy-related) mechanisms. In patients with compensated disease, ACE-I/ARB were not associated with hepatic decompensation or HCC. Future research should identify subsets of patients who benefit from ACE-I/ARB exposure.
血管紧张素转换酶抑制剂（ACE-I）和血管紧张素受体阻滞剂（ARB）可能对主要患有慢性肝病的患者有肝脏益处。ACE-I/ARB尚未在包括失代偿期肝硬化患者在内的广泛队列中进行评估。我们分析了全国队列中ACE-I/ARB暴露与肝硬化相关结局之间的真实世界关联。
我们对退伍军人健康管理局中肝硬化患者进行了一项回顾性、活性对照新使用者研究。我们确定了ACE-I/ARB或钙通道阻滞剂（对照）的新使用者。逆概率处理加权平衡了关键混杂因素，Cox回归评估了ACE-I/ARB与死亡率、肝硬化失代偿和肝细胞癌（HCC）结局之间的关联。在探索性分析中，特定病因竞争风险模型评估了肝脏相关、心血管（CV）相关和非肝脏/非CV相关死亡率。
有904名ACE-I/ARB新使用者和352名钙通道阻滞剂新使用者。在逆概率处理加权Cox回归中，ACE-I/ARB暴露与死亡率降低相关（风险比[HR]0.70，95%置信区间[CI]0.61-0.81，P<0.001）。在代偿期肝硬化患者中，ACE-I/ARB与肝失代偿或HCC无关。特定病因风险模型显示，ACE-I/ARB暴露与非肝脏/非CV相关死亡率降低相关（特定病因HR 0.49，95%CI 0.38-0.62，P<0.001），但与肝脏相关或CV相关死亡率无关。在Child-Turcotte-Pugh A级患者中，ACE-I/ARB与CV相关死亡率降低相关（特定病因HR 0.41，95%CI 0.26-0.65，P<0.001）。
ACE-I/ARB暴露与死亡率降低相关，可能通过心血管和其他（肾脏、恶性肿瘤相关）机制。在病情代偿的患者中，ACE-I/ARB与肝失代偿或HCC无关。未来的研究应确定从ACE-I/ARB暴露中获益的患者亚组。
