英国伦敦大学学院肝脏和消化健康研究所Alastair O’Brien团队研究了肝硬化住院患者输注白蛋白的疗效。2021年3月4日，该研究发表在《新英格兰医学杂志》上。

感染和全身炎症增加导致失代偿期肝硬化患者的器官功能障碍和死亡。临床前研究为白蛋白的抗炎作用提供了支持，但尚缺乏验证性的大规模临床试验。与标准治疗相比，患者每天重复输注20%人白蛋白溶液，血清白蛋白水平是否可达到30g/L或更高，是否能降低感染、肾功能不全和死亡的发生率尚不清楚。

研究组进行了一项随机、多中心、开放标签、平行组试验，招募失代偿期肝硬化住院患者，这些患者在登记时的血清白蛋白水平低于30g/L。将其随机分配，分别接受靶向20%人白蛋白溶液长达14天或直到出院，或接受标准治疗。入院后3天内开始治疗。复合主要终点是开始治疗后第3天至第15天的新感染、肾功能不全或死亡。

共有777名患者接受了随机分组，据报道酒精是大多数患者肝硬化的原因。靶向白蛋白组（将白蛋白水平增加至≥30g/l）中每位患者中位输注白蛋白200g，而标准治疗组仅为20g，差异显著。靶向白蛋白组中有29.7%的患者发生主要终点事件，标准治疗组中有30.2%，无显著差异。在出院时或第15天对数据进行删失的时间-事件分析也显示组间差异无显著性。与标准治疗组相比，白蛋白组发生更多严重或危及生命的不良事件。

研究结果表明，对于失代偿期肝硬化住院患者，输注白蛋白将白蛋白水平提高到30g/L及以上并不比英国目前的标准治疗更有益。

附：英文原文

Title: A Randomized Trial of Albumin Infusions in Hospitalized Patients with Cirrhosis

Author: Louise China, Ph.D.,, Nick Freemantle, Ph.D.,, Ewan Forrest, M.D.,, Yiannis Kallis, Ph.D.,, Stephen D. Ryder, D.M.,, Gavin Wright, Ph.D.,, Andrew J. Portal, M.D.,, Natalia Becares Salles, Ph.D.,, Derek W. Gilroy, Ph.D.,, and Alastair O’Brien, Ph.D.

Issue&Volume: 2021-03-03

Abstract:

Background

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.

Methods

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.

Results

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.

Conclusions

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.

DOI: 10.1056/NEJMoa2022166

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2022166