Treatment with carvedilol improves survival of patients with acute-on-chronic liver failure: a randomized controlled trial
Background and aims
In addition to the portal pressure reducing effect, non-selective beta blockers (NSBBs) have possible immunomodulatory and effect in reducing bacterial translocation. Recently, it has been shown that patients who are already on NSBBs should be continued on them (if feasible), if acute-on-chronic liver failure (ACLF) develops. It, however, remains unknown if patients with ACLF and no or small esophageal varices at presentation will benefit from the use of NSBBs. We studied the efficacy and safety of carvedilol in patients with ACLF in reducing mortality, variceal bleeding and non-bleeding complications.
136 patients with ACLF (with no or small esophageal varices and HVPG ≥ 12 mmHg) were randomized to either carvedilol (n = 66) or placebo arms (n = 70).
Within 28 days, 7 (10.6%) of 66 patients in the carvedilol group and 17 (24.3%) of 70 in the placebo group died (p= 0.044). Fewer patients in the carvedilol compared to placebo group developed acute kidney injury (AKI) (13.6% vs 35.7%, p = 0.003 and spontaneous bacterial peritonitis (SBP) (6.1% vs 21.4%, p= 0.013). Significantly, more patients in the placebo group had increase in APASL ACLF Research Consortium-ACLF grade (22.9% vs 6.1%, p= 0.007). There was no significant difference in the 90-day transplant-free survival rate and development of AKI, SBP, non-SBP infections (including pneumonia) and variceal bleed within 90 days, between the two groups.
In ACLF patients with either no or small esophageal varices and HVPG ≥ 12 mmHg, carvedilol leads to improved survival and fewer AKI and SBP events up to 28 days.
ClinicalTrials.gov identifier number
KeywordsAcute-on-chronic liver failure Beta blockers Carvedilol
APASL ACLF Research Consortium
Acute-on-chronic liver failure
Acute kidney injury
Asian Pacific Association for the Study of the Liver
Chronic Liver Failure Consortium
Drug-induced liver injury
Free hepatic venous pressure
Hepatitis B virus
Hepatitis E virus
Hepatic venous pressure gradient
International normalized ratio
Non-selective beta blocker
Wedged hepatic venous pressure
We thank SK, MK and SKS for developing the protocol; SK, MKS, SKS and AB for enrolling participants in the study; RM, AC, LGM, VS, PA, SSM, AJ and SKS for reviewing and providing inputs to the protocol and manuscript; and GK for helping with statistical analysis.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
The study has been approved by the institutional ethics committee of the Institute of Liver and Biliary Sciences (Letter no. F.25/5/80/ILBS/AC/2015/711) and has been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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