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

Abstract

At present, non-selective beta-blockers (NSBBs) are recommended for the management of clinically significant portal hypertension and primary or secondary prophylaxis of variceal bleeding in cirrhosis [1, 2]. However, as mentioned in the editorial by Alferink and de Knegt [3], the right time to discontinue NSBBs remains inconclusive. The window hypothesis, which has been for the first time proposed by Krag et al. suggests that the beneficial effects of NSBBs may be lost in end-stage cirrhosis [4]. Since then, numerous studies have confirmed their deleterious effects in some specified populations (Table 1), which may negatively correlate with the Model of End-Stage Liver Disease (MELD) score [5]. In a previous meta-analysis by our group, the use of NSBBs significantly increased the risk of renal dysfunction in patients with a MELD score of > 15 [6]. Calès et al. also found that the use of NSBBs worsened the survival in patients with a MELD score of > 12 [7]. Similarly, our current study further suggested that NSBBs should increase the risk of further decompensation in decompensated patients with a MELD score of > 9 [8].

As pointed out in the editorial by Alferink and de Knegt mentioned above [3], there was a significant interaction between the MELD score and the use of NSBBs in our current study. Accordingly, we compared the incidence of further decompensation stratified by MELD score deciles between the NSBBs group and the non-NSBBs group. We found that a MELD score of 9 should be a specific turning point to identify a bidirectional impact of NSBBs on the risk of further decompensation in cirrhosis. Specifically, NSBBs may be harmful in patients whose MELD score is above nine, and vice versa.

As outlined in the editorial [3], there were some limitations in our current study. First, the retrospective study design may cause bias in patient selection and recall. Thus, propensity score matching analyses were performed to minimise known and unknown confounders. Second, only Chinese patients were included, thus, our findings may not be generalisable. Third, our patients needed a relatively low dosage of propranolol, probably due to their differences in body constitution and ethnics from other regions, which is consistent with the dosage of propranolol used in many previous studies from China [9, 10]. Lastly, all patients included in our study had been treated with propranolol. Therefore, it was impossible to identify whether carvedilol could also cause such a bidirectional effect on the patients' outcomes.

Regardless, our findings further support the window hypothesis of NSBBs in cirrhosis. However, we require more solid evidence to determine which is the right time to discontinue NSBBs.

Ting Wang: conceptualization, writing – original draft, investigation, visualization. Deli Zou: conceptualization, investigation, visualization. Xingshun Qi: conceptualization, investigation, supervision, writing – review and editing.

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.18334.