From the Institute for Liver and Digestive Health (L.C., N.B.S., A.O.), the Comprehensive Clinical Trials Unit (N.F.), and the Division of Medicine, University College London (D.W.G.), Barts and the London School of Medicine and Dentistry, Queen Mary University of London (Y.K.), London, the Glasgow Royal Infirmary and the University of Glagow, Glasgow (E.F.), the National Institute for Health Research Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust and the University of Nottingham, Queens Medical Centre, Nottingham (S.D.R.), the Mid and South Essex NHS Foundation Trust and the Basildon and Thurrock University Hospitals NHS Foundation Trust, Basildon (G.W.), and the Bristol Royal Infirmary, Bristol (A.J.P.) - all in the United Kingdom.
N Engl J Med. 2021 Mar 4;384(9):808-817. doi: 10.1056/NEJMoa2022166.
Infection and increased systemic inflammation cause organ dysfunction and death in patients with decompensated cirrhosis. Preclinical studies provide support for an antiinflammatory role of albumin, but confirmatory large-scale clinical trials are lacking. Whether targeting a serum albumin level of 30 g per liter or greater in these patients with repeated daily infusions of 20% human albumin solution, as compared with standard care, would reduce the incidences of infection, kidney dysfunction, and death is unknown.
We conducted a randomized, multicenter, open-label, parallel-group trial involving hospitalized patients with decompensated cirrhosis who had a serum albumin level of less than 30 g per liter at enrollment. Patients were randomly assigned to receive either targeted 20% human albumin solution for up to 14 days or until discharge, whichever came first, or standard care. Treatment commenced within 3 days after admission. The composite primary end point was new infection, kidney dysfunction, or death between days 3 and 15 after the initiation of treatment.
A total of 777 patients underwent randomization, and alcohol was reported to be a cause of cirrhosis in most of these patients. A median total infusion of albumin of 200 g (interquartile range, 140 to 280) per patient was administered to the targeted albumin group (increasing the albumin level to ≥30 g per liter), as compared with a median of 20 g (interquartile range, 0 to 120) per patient administered to the standard-care group (adjusted mean difference, 143 g; 95% confidence interval [CI], 127 to 158.2). The percentage of patients with a primary end-point event did not differ significantly between the targeted albumin group (113 of 380 patients [29.7%]) and the standard-care group (120 of 397 patients [30.2%]) (adjusted odds ratio, 0.98; 95% CI, 0.71 to 1.33; P = 0.87). A time-to-event analysis in which data were censored at the time of discharge or at day 15 also showed no significant between-group difference (hazard ratio, 1.04; 95% CI, 0.81 to 1.35). More severe or life-threatening serious adverse events occurred in the albumin group than in the standard-care group.
In patients hospitalized with decompensated cirrhosis, albumin infusions to increase the albumin level to a target of 30 g per liter or more was not more beneficial than the current standard care in the United Kingdom. (Funded by the Health Innovation Challenge Fund; ATTIRE EudraCT number, 2014-002300-24; ISRCT number, N14174793.).
感染和全身性炎症增加会导致失代偿性肝硬化患者的器官功能障碍和死亡。临床前研究支持白蛋白具有抗炎作用，但缺乏确证性的大规模临床试验。在这些患者中，每日重复输注 20%人血白蛋白溶液，将血清白蛋白水平靶向 30 克/升或更高，与标准治疗相比，是否会降低感染、肾功能障碍和死亡的发生率尚不清楚。
我们进行了一项随机、多中心、开放标签、平行组试验，纳入了入院时血清白蛋白水平低于 30 克/升的失代偿性肝硬化住院患者。患者被随机分配接受目标 20%人血白蛋白溶液治疗，最长 14 天，或直至出院（以先发生者为准），或接受标准治疗。治疗在入院后 3 天内开始。主要复合终点是治疗开始后第 3 至 15 天的新发感染、肾功能障碍或死亡。
共有 777 名患者接受了随机分组，其中大多数患者报告的肝硬化病因是酒精。目标白蛋白组（将白蛋白水平提高到≥30 克/升）的中位总白蛋白输注量为每例患者 200 克（四分位距 140 至 280），而标准治疗组的中位数为每例患者 20 克（四分位距 0 至 120）（校正平均差异 143 克；95%置信区间 127 至 158.2）。主要终点事件的患者比例在目标白蛋白组（380 例患者中的 113 例[29.7%]）和标准治疗组（397 例患者中的 120 例[30.2%]）之间无显著差异（校正优势比 0.98；95%置信区间 0.71 至 1.33；P=0.87）。数据在出院或第 15 天时截尾的时间事件分析也显示两组间无显著差异（风险比 1.04；95%置信区间 0.81 至 1.35）。白蛋白组较标准治疗组更易发生严重或危及生命的严重不良事件。
在英国，与目前的标准治疗相比，输注白蛋白将白蛋白水平提高到 30 克/升或更高水平，对因失代偿性肝硬化住院的患者并没有更多益处。（由健康创新挑战赛基金资助；ATTIRE EudraCT 编号，2014-002300-24；ISRCTN 编号，N14174793。）
