Tittanegro Thais, China Louise, Forrest Ewan, Kallis Yiannis, Ryder Stephen D, Wright Gavin, Freemantle Nick, O'Brien Alastair
Institute of Liver and Digestive Health, University College London, United Kingdom.
Glasgow Royal Infirmary, Glasgow, United Kingdom.
EClinicalMedicine. 2022 Nov 14;55:101716. doi: 10.1016/j.eclinm.2022.101716. eCollection 2023 Jan.
Nonselective B-blockers (NSBBs) are believed to have pleiotropic effects beyond reducing portal pressure. However, studies also report potential harm in patients hospitalized with cirrhosis and ascites. We therefore investigated whether NSBB use at ATTIRE trial entry (Albumin to prevent infection in chronic liver failure, 2016-19) was associated with increased renal or cardiovascular dysfunction, compared the incidence of infection and plasma markers of systemic inflammation, and examined mortality at 28-days, 3 and 6-months.
In ATTIRE patients grouped by NSBB use at trial entry, we studied infection at baseline, hospital acquired infection and organ dysfunction during trial treatment period and mortality, with propensity score matching to account for differences in disease severity.
There were no differences in renal or cardiovascular dysfunction between patients treated with NSBBs or not, during days 3-15 of hospitalization, despite elevated serum creatinine in NSBB patients at hospitalisation. Use of NSBBs was associated with a significant reduction in infection at hospitalization ( = 0.006), lower white cell counts throughout hospital stay ( < 0.001) and reduced plasma procalcitonin ( = 0.009) and interlukin-8 levels ( = 0.04) at baseline, but markers of bacterial translocation and systemic inflammation were the same in treatment groups. There was no reduction in hospital acquired infections in patients taking NSBBs and no beneficial impact on mortality at 28-days, 3 and 6-months.
Our real-world data from a completed randomised trial show that use of NSBBs in decompensated cirrhosis patients is safe during hospitalisation. We also show a potential anti-inflammatory role for NSBBs which may be mediated by a downregulation of IL-8 induced leucocytosis, that was associated with reduced infection at baseline but not a survival benefit.
Wellcome Trust and Department of Health and Social Care.
非选择性β受体阻滞剂（NSBBs）被认为除了降低门静脉压力外还具有多效性作用。然而，研究也报告了其对肝硬化腹水住院患者的潜在危害。因此，我们调查了在“服装试验”（白蛋白预防慢性肝衰竭感染，2016 - 19年）入组时使用NSBBs是否与肾脏或心血管功能障碍增加相关，比较了感染发生率和全身炎症的血浆标志物，并检查了28天、3个月和6个月时的死亡率。
在“服装试验”中，根据入组时是否使用NSBBs对患者进行分组，我们研究了基线时的感染情况、试验治疗期间的医院获得性感染和器官功能障碍以及死亡率，并采用倾向评分匹配法来考虑疾病严重程度的差异。
在住院第3 - 15天，使用NSBBs的患者与未使用的患者在肾脏或心血管功能障碍方面没有差异，尽管使用NSBBs的患者住院时血清肌酐升高。使用NSBBs与住院期间感染显著减少（P = 0.006）、整个住院期间白细胞计数降低（P < 0.001）以及基线时血浆降钙素原降低（P = 0.009）和白细胞介素 - 8水平降低（P = 0.04）相关，但治疗组之间细菌移位和全身炎症的标志物相同。使用NSBBs的患者医院获得性感染没有减少，对28天、3个月和6个月时的死亡率也没有有益影响。
我们来自一项已完成的随机试验的真实世界数据表明，在失代偿期肝硬化患者住院期间使用NSBBs是安全的。我们还表明NSBBs具有潜在的抗炎作用，这可能是由IL - 8诱导的白细胞增多的下调介导的，这与基线时感染减少相关，但对生存没有益处。
惠康信托基金会以及卫生和社会保健部。
