The role of albumin infusion in overt hepatic encephalopathy in liver cirrhosis

Bai Z, Bernardi M, Yoshida EM, Li H, Guo X, Méndez-Sánchez N, Li Y, Wang R, Deng J, Qi X 

Aging (Albany NY) 2019;11:8502–8525

• The role of albumin infusion in the prevention and treatment of overt hepatic encephalopathy (HE) in cirrhotic patients is subject to debate 
• The following study combines the results of a retrospective observational study with a systematic review of the existing literature on this topic 
• Discover the extent to which albumin infusion might prevent and/or reduce severity of HE in cirrhotic patients and reduce in-hospital deaths 

HE is a disorder of the brain that occurs as a result of hepatic insufficiency or portosystemic shunting (AASLD & EASL, 2014). With a reported incidence of 30–45% in patients with liver cirrhosis and 1-year and 3-year survival rates of <50% and <25% respectively, HE represents a serious risk to these individuals and places a significant burden on global healthcare services (Bai et al., 2019). 

At its broadest level of classification, HE can be divided into two distinct subcategories: overt and covert HE. Covert HE is characterised by neuropsychological and/or neurophysiological abnormalities in the absence of disorientation or asterixis (AASLD & EASL, 2014). By contrast, clinical signs are very apparent in cases of overt HE, allowing the severity of a patient’s condition to be assessed using the West-Haven criteria (Blei & Cordoba, 2001). Underlying liver disease can also be used to distinguish HE subtypes (AASLD & EASL, 2014). 

Currently available treatments for HE target several potential pathogeneses, which include hyperammonaemia, increased inhibitory function of gamma-aminobutyric acid (GABA), bacterial infection and inflammation (Poh & Chang, 2012). More recently, reports of improvements to systemic inflammatory responses following albumin infusion have emerged, leading to further studies in patients with overt HE (Artigas et al., 2016). However, to date, the findings of studies investigating albumin infusions in both prevention and treatment of overt HE have been highly inconsistent, resulting in international discrepancies in current recommendations for treating patients with HE and those at high risk of developing the condition (AASLD & EASL, 2014; Montagnese et al., 2019). 

This study combined the findings of a retrospective observational study and systematic review and meta-analysis of existing literature to further elucidate the role of albumin infusion in the prevention and treatment of HE in liver cirrhosis:

Main Findings

1. There was an association between albumin infusion and reduced incidence and improvement of overt HE. According to the meta-analysis carried out:

• The number needed to treat (NNT) for preventing the development of overt HE was 14 (95% CI = 8 to 46).
• The NNT for improving severity of overt HE was 5 (95% CI = 4 to 6)

2. There might be an association between albumin infusion and reduced in-hospital mortality in cirrhotic patients both with and without overt HE.

The retrospective observational component of this study was a limitation, with an inherent risk of selection bias and misclassification, as well as lacking a standard dosage of albumin. There was also a small number of studies in the meta-analysis, and heterogeneity of patient characteristics, duration and dosage of albumin, and use of other drugs for the management of overt HE between the studies. Other limitations were that it included only absolute numbers of patients who developed HE events, not cumulative incidence of HE or number of HE events, and results of the meta-analysis might have been influenced by the fact that this study only reported the occurrence of grade III or IV HE and follow-up for patients who had only received standard medical treatment was considerably shorter than for those who also received albumin.

Further research and prospective studies will be required to confirm the mechanism by which the benefits of albumin infusion in overt HE management arise.