Kumar Rahul, Lin Su, Mehta Gautam, Mesquita Monica D, Calvao Joana A F, Sheikh M Faisal, Agarwal Banwari, Mookerjee R P, Jalan Rajiv
Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, London, UK.
Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore.
Aliment Pharmacol Ther. 2024 Oct;60(7):907-920. doi: 10.1111/apt.18188. Epub 2024 Aug 1.
Apart from direct portal pressure reduction, non-selective beta-blockers (NSBB) modulate inflammatory response, which could be beneficial in patients with acute decompensation (AD). We therefore aimed to evaluate the effect of NSBB on 28-day mortality and markers of systemic inflammation in a propensity score-matched (PSM) cohort of AD patients requiring intensive care unit (ICU) admission.
Patients were recruited from registry of AD patients requiring ICU admission. Out of total 445 patients, 108 patients on NSBB before admission (NSBB use group) were PSM for age, gender, pre-admission Child-Turcotte-Pugh score and history of previous decompensation to 108 patients not on NSBB (non-NSBB use group) which served as the control group. ICU parameters, markers of systemic inflammation and 28-day mortality were compared by standard statistical tests.
After PSM, no difference was observed in aetiology of cirrhosis, or precipitating event for AD between the groups. Pre-admission creatinine, bilirubin, international normalised ratio and haemoglobin were similar between the groups, whereas pre-admission white cell count (WCC) and neutrophil to lymphocyte ratio (NLR) was lower in NSBB-group. On admission to ICU, NSBB group had lower heart rate (p = 0.006), platelets (p = 0.012), WCC (p = 0.006), NLR (p = 0.039) and C-reactive protein (p = 0.007). Significantly more community acquired bacterial infections (p = 0.006), renal failure (p = 0.033) and higher grades of acute-on-chronic liver failure (ACLF; p = 0.012) were observed in non-NSBB group. Significantly lower 28-day (p = 0.001) and 90-day (p = 0.002) mortality was seen in NSBB group. Univariate and multivariable analysis for 28-day mortality showed that while ACLF at presentation and community acquired bacterial infection were independent negative predictors, prior NSBB use was positive predictors of survival.
Prior use of NSBB is associated with improved 28- and 90-day mortality in critically ill cirrhosis patients with AD which is mediated probably by blunting of the inflammatory response.
除直接降低门静脉压力外，非选择性β受体阻滞剂（NSBB）可调节炎症反应，这可能对急性失代偿（AD）患者有益。因此，我们旨在评估NSBB对需要入住重症监护病房（ICU）的AD患者倾向评分匹配（PSM）队列中28天死亡率和全身炎症标志物的影响。
从需要入住ICU的AD患者登记处招募患者。在总共445例患者中，将入院前使用NSBB的108例患者（NSBB使用组）按年龄、性别、入院前Child-Turcotte-Pugh评分和既往失代偿史与108例未使用NSBB的患者（非NSBB使用组）进行PSM匹配，后者作为对照组。通过标准统计检验比较ICU参数、全身炎症标志物和28天死亡率。
PSM后，两组间肝硬化病因或AD的诱发事件无差异。两组间入院前肌酐、胆红素、国际标准化比值和血红蛋白相似，而NSBB组入院前白细胞计数（WCC）和中性粒细胞与淋巴细胞比值（NLR）较低。入住ICU时，NSBB组心率较低（p = 0.006）、血小板较低（p = 0.012）、WCC较低（p = 0.006）、NLR较低（p = 0.039）和C反应蛋白较低（p = 0.007）。非NSBB组社区获得性细菌感染（p = 0.006）、肾衰竭（p = 0.033）和更高等级的慢加急性肝衰竭（ACLF；p = 0.012）明显更多。NSBB组28天（p = 0.001）和90天（p = 0.002）死亡率明显更低。对28天死亡率的单因素和多因素分析表明，虽然入院时的ACLF和社区获得性细菌感染是独立的负性预测因素，但既往使用NSBB是生存的正性预测因素。
既往使用NSBB与AD的重症肝硬化患者28天和90天死亡率改善相关，这可能是通过减轻炎症反应介导的。
