Non-selective beta-blockers increase overall and liver mortality in alcoholic cirrhosis with MELD≥12 over 5 years of follow-up.

Abstract

Non-cardioselective beta-blocker (NSBB) effects on mortality in cirrhosis are controversial. We evaluated the impact of NSBBs on mortality according to liver severity and mortality cause. Two hundred and fifty-eight patients with alcoholic cirrhosis were included in a retroprospective cohort: 129 NSBB-treated and 129 controls. The NSBB group had the following significant baseline differences: higher MELD, more frequent previous gastrointestinal bleeding, large oesophageal varices (OV) and lower heart rate. Propranolol dose was 160mg/d in 81% of NSBB patients. (i) Liver function: during 5.3 ± 2.6 years of follow-up, MELD progression was higher in NSBB patients: 1 (-1-4) than in controls: 0 (-1-1) (P = .017). (ii) Overall survival: no significant differences were observed between NSBBs and controls (Kaplan-Meier curves: P=.291). In multivariate Cox analysis, baseline MELD interacted with NSBB (P=.011). Thus, the NSBB hazard ratio (HR) was 0.99 (0.50-1.98) in MELD<12 vs 3.17 (1.19-8.42) in MELD≥12. (iii) Liver survival: NSBB decreased liver survival (Kaplan-Meier: P=.031). In multivariate Cox analysis, baseline MELD interacted with NSBB (P<.001). The NSBB HR was 0.81 (0.30-2.19) in MELD<12 vs 6.23 (1.94-20.0) in MELD≥12. In competing risk multivariate analysis for liver mortality, the MELD-NSBB interaction was significant (P<.001): the NSBB HR was 1.02 (0.36-2.91) in MELD<12 vs 9.24 (3.18-26.9) in MELD≥12. 4) Non-liver survival: contrastingly, non-liver survival was increased by NSBBs, especially in MELD≥12 (competing Kaplan-Meier: P=.044). These results were confirmed in propensity risk score (PRS)-matched patients. In alcoholic cirrhosis with rather high propranolol doses, overall and liver survival are significantly aggravated when MELD is ≥12.