Department of Medical and Surgical Sciences, University of Bologna, Italy; Bologna University Hospital Authority St. Orsola-Malpighi Polyclinic, Italy.
Department of Clinical Medicine, "Sapienza" University of Rome, Italy.
J Hepatol. 2021 Feb;74(2):340-349. doi: 10.1016/j.jhep.2020.08.021. Epub 2020 Aug 24.
BACKGROUND & AIMS: The ANSWER study reported that long-term albumin administration in patients with cirrhosis and uncomplicated ascites improves survival. During treatment, serum albumin increased within a month and remained stable thereafter. In this post hoc analysis, we aimed to determine whether on-treatment serum albumin levels could guide therapy.
Logistic regression was used to assess the association between baseline serum albumin and mortality, as well as to determine on-treatment factors associated with mortality and to predict the achievement of a given on-treatment serum albumin level. Survival was assessed by Kaplan-Meier estimates and second-order polynomial regression. Patients whose on-treatment serum albumin remained below normal were compared with a subset of patients from the control arm matched by principal score.
Baseline serum albumin was closely associated with 18-month mortality in untreated patients; albumin treatment almost effaced this relationship. On-treatment serum albumin and MELD-Na at month 1 were the sole independent variables associated with mortality. Second-order polynomial regression revealed that survival improved in parallel with increased 1-month on-treatment serum albumin. Kaplan-Meier estimations showed that any value of 1-month on-treatment serum albumin (0.1 g/dl intervals) in the range 2.5-4.5 g/dl discriminated patient survival. In the normal range of serum albumin, the best discriminant value was 4.0 g/dl. Compared to untreated patients, survival even improved in patients whose on-treatment serum albumin remained below normal.
Baseline serum albumin per se should not guide the decision to start albumin therapy. Conversely, 1-month on-treatment serum albumin levels are strongly associated with outcomes and could guide the use of albumin - 4.0 g/dl being the target threshold. However, even patients whose serum albumin remains below normal benefit from long-term albumin administration.
The ANSWER study has shown that long-term albumin administration improves survival and prevents the occurrence of major complications in patients with cirrhosis and ascites. This study shows that the achievement of these beneficial effects is related to a significant increase in serum albumin concentration. Even though the best results follow the achievement of a serum albumin concentration of 4 g/dl, a survival benefit is also achieved in patients who fail to normalise serum albumin.
ANSWER 研究报告称，长期给予肝硬化伴单纯性腹水患者白蛋白可改善生存率。治疗期间，血清白蛋白在一个月内增加，并在此后保持稳定。在本事后分析中，我们旨在确定治疗中的血清白蛋白水平是否可以指导治疗。
使用逻辑回归评估基线血清白蛋白与死亡率之间的关系，以及确定与死亡率相关的治疗中因素，并预测达到特定治疗中血清白蛋白水平。通过 Kaplan-Meier 估计和二阶多项式回归评估生存情况。将治疗中血清白蛋白持续低于正常水平的患者与通过主要评分匹配的对照组中的亚组患者进行比较。
基线血清白蛋白与未经治疗患者的 18 个月死亡率密切相关；白蛋白治疗几乎消除了这种关系。治疗中血清白蛋白和 1 个月时的 MELD-Na 是与死亡率相关的唯一独立变量。二阶多项式回归显示，随着 1 个月时治疗中血清白蛋白的增加，生存情况得到改善。Kaplan-Meier 估计显示，治疗中 1 个月血清白蛋白的任何值（0.1 g/dl 间隔）在 2.5-4.5 g/dl 范围内可区分患者的生存情况。在正常的血清白蛋白范围内，最佳区分值为 4.0 g/dl。与未经治疗的患者相比，即使治疗中血清白蛋白仍低于正常水平的患者的生存情况也得到了改善。
基线血清白蛋白本身不应指导开始白蛋白治疗的决定。相反，1 个月时的治疗中血清白蛋白水平与结局密切相关，并可指导白蛋白的使用-4.0 g/dl 是目标阈值。然而，即使是血清白蛋白仍低于正常水平的患者也从长期白蛋白治疗中获益。
ANSWER 研究表明，长期给予白蛋白可改善肝硬化伴腹水患者的生存率并预防主要并发症的发生。本研究表明，这些有益效果的实现与血清白蛋白浓度的显著增加有关。尽管达到 4 g/dl 的血清白蛋白浓度可获得最佳结果，但未能使血清白蛋白正常化的患者也可获得生存获益。
