Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free Hospital, London, United Kingdom.
European Foundation for the Study of Chronic Liver Failure (EF-CLIF) and EASL-CLIF Consortium.
J Hepatol. 2016 Mar;64(3):574-82. doi: 10.1016/j.jhep.2015.10.018. Epub 2015 Oct 28.
BACKGROUND & AIMS: Non-selective beta blockers (NSBBs) have been shown to have deleterious outcomes in patients with refractory ascites, alcoholic hepatitis and spontaneous bacterial peritonitis leading many physicians to stop the drug in these cases. Acute-on-chronic liver failure (ACLF) is characterized by systemic inflammation and high mortality. As NSBBs may have beneficial effects on gut motility and permeability and, systemic inflammation, the aims of this prospective, observational study were to determine whether ongoing use of NSBBs reduced 28-day mortality in ACLF patients.
The study was performed in 349 patients with ACLF included in the CANONIC study, which is a prospective observational investigation in hospitalized cirrhotic patients with acute deterioration. The data about the use of NSBBs, its type and dosage was specifically recorded. Patient characteristics at enrollment significantly associated with treatment and mortality were taken into account as potential confounders to adjust for treatment effect. A logistic regression model was fitted.
164 (47%) ACLF patients received NSBBs whereas 185 patients did not. Although the CLIF-C ACLF scores were similar at presentation, more patients in the NSBB treated group had lower grades of ACLF (p=0.047) at presentation and significantly more patients improved. Forty patients (24.4%) died in NSBB treated group compared with 63 patients (34.1%) (p=0.048) [estimated risk-reduction 0.596 (95%CI: 0.361-0.985; p=0.0436)]. This improvement in survival was associated with a significantly lower white cell count (NSBB: 8.5 (5.8); no NSBB: 10.8 (6.6); p=0.002). No long-term improvement in survival was observed.
This study shows for the first time that ongoing treatment with NSBBs in cirrhosis is safe and reduces the mortality if they develop ACLF. Careful thought should be given before stopping NSBBs in cirrhotic patients.
非选择性β受体阻滞剂(NSBBs)已被证明在难治性腹水、酒精性肝炎和自发性细菌性腹膜炎患者中具有不良结局,这导致许多医生在这些情况下停止使用该药物。慢加急性肝衰竭(ACLF)的特征是全身炎症和高死亡率。由于 NSBBs 可能对肠道动力和通透性以及全身炎症具有有益影响,本前瞻性观察性研究旨在确定在 ACLF 患者中持续使用 NSBB 是否降低 28 天死亡率。
该研究在 349 例 ACLF 患者中进行,这些患者均纳入 CANONIC 研究,这是一项对住院肝硬化患者急性恶化的前瞻性观察性研究。专门记录了 NSBB 的使用、类型和剂量的数据。将与治疗和死亡率显著相关的患者特征作为潜在混杂因素纳入,以调整治疗效果。拟合了逻辑回归模型。
164 例(47%)ACLF 患者接受了 NSBBs 治疗,而 185 例患者未接受 NSBBs 治疗。尽管 CLIF-C ACLF 评分在发病时相似,但 NSBB 治疗组的患者在发病时具有较低的 ACLF 分级(p=0.047),且显著更多的患者得到改善。在 NSBB 治疗组中,有 40 例(24.4%)患者死亡,而在未接受 NSBB 治疗组中,有 63 例(34.1%)患者死亡(p=0.048)[估计风险降低 0.596(95%CI:0.361-0.985;p=0.0436)]。这种生存改善与白细胞计数的显著降低相关(NSBB:8.5(5.8);无 NSBB:10.8(6.6);p=0.002)。未观察到长期生存改善。
本研究首次表明,在肝硬化患者中持续使用 NSBBs 是安全的,如果发生 ACLF,可降低死亡率。在停止肝硬化患者使用 NSBBs 之前,应慎重考虑。