Editorial: Navigating the Beta-Blocker Dilemma in Advanced Liver Cirrhosis—When Is the Right Time to Discontinue?

Abstract

Non-selective beta-blockers (NSBBs) are highly effective in preventing variceal bleeding. They are therefore widely used in patients with liver cirrhosis and portal hypertension [1]. Since the landmark study by Lebrec et al. many studies have investigated NSBB use in cirrhosis, including the controversial paper by Serste et al. which suggested increased mortality in decompensated cirrhosis due to NSBB use [2]. Despite its methodological limitations, this study sparked extensive research on NSBBs in decompensated cirrhosis. Krag et al. thereafter introduced the ‘window hypothesis’, proposing that NSBBs might harm patients with advanced liver cirrhosis by reducing cardiac output in those already at risk of low organ perfusion [3]. However, NSBBs not only reduce portal pressure, they may also possess anti-inflammatory effects [4]. Therefore, NSBB use is advocated in all patients with clinically significant portal hypertension, not just in those with oesophageal varices [5]. Nonetheless, the safety of NSBBs in patients with decompensated cirrhosis, particularly those with acute kidney injury (AKI)/hepatorenal syndrome (HRS), and refractory ascites, remains controversial.

The study by Wang et al. explores NSBB safety in a hospitalised Asian population with already decompensated cirrhosis and finds that NSBBs did not affect further decompensation nor overall survival [6]. However, a significant interaction between admission MELD-score and NSBB use justified a stratified analysis by MELD-score (low [≤ 9] vs. high MELD-scores [> 9]). NSBB use was associated with a lower risk of further decompensation in the low MELD group but a higher risk of further decompensation in the high MELD group. This stratified analysis did not show an association with overall survival. Advantages of this study are the population size (N = 332) with a sufficient number of events and median follow-up of almost 4 years. It highlights a very relevant and timely topic. However, the limitations of this study must also be considered. As this was an all-Asian population using low-dose propranolol, the generalisability of this study is limited. Also, many studies have shown an advantage of carvedilol over traditional NSBBs, which is now also advocated by the BAVENO VII consensus [5, 7, 8]. Furthermore, the retrospective study design may have introduced bias. Finally, clearer justification for the MELD-9 cut-off, perhaps using visual splines, would have been helpful.

Building upon this current study there seems to be a non-linear association between NSBB benefit and liver disease severity. Efforts have been made to define this specific turning point in which NSBB may be detrimental rather than beneficial. In the current BAVENO VII consensus this point is defined by a persistent systolic blood pressure of < 90 mmHg or the presence of AKI/HRS [5]. It is difficult to draw definitive conclusions on this issue based on previous studies due to heterogeneity in NSBB type and dosage, aetiology-skewed or selected study populations, in definition of portal hypertension and/or in design (often retrospective and non-randomised). Also, further studies on the safety of stopping and restarting NSBBs are needed, while there is limited evidence on this topic [9]. In conclusion, the study by Wang et al. highlights an important and timely issue, raising new and relevant questions for future research.

Louise J. M. Alferink: writing – original draft, writing – review and editing. Robert J. de Knegt: conceptualization, writing – review and editing, supervision.

The authors declare no conflicts of interest.

This article is linked to Wang et al papers. To view these articles, visit https://doi.org/10.1111/apt.18261 and https://doi.org/10.1111/apt.18371.