Hepatology International

, Volume 13, Issue 6, pp 800–813 | Cite as

Treatment with carvedilol improves survival of patients with acute-on-chronic liver failure: a randomized controlled trial

  • Manoj KumarEmail author
  • Sumit Kainth
  • Ashok Choudhury
  • Rakhi Maiwall
  • Lalita G. Mitra
  • Vandana Saluja
  • Prashant Mohan Agarwal
  • Saggere Muralikrishna Shasthry
  • Ankur Jindal
  • Ankit Bhardwaj
  • Guresh Kumar
  • Shiv K. Sarin
Original Article


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. identifier number



Acute-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


Hepatic encephalopathy


Hepatitis E virus


Hepatic venous pressure gradient


International normalized ratio


Liver transplantation


Non-alcoholic steatohepatitis


Non-selective beta blocker


Wedged hepatic venous pressure


Author contributions

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.

Ethical standards

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

Informed consent was obtained from all individual participants included in the study.

Supplementary material

12072_2019_9986_MOESM1_ESM.doc (71 kb)
Supplementary material 1 (DOC 71 kb)
12072_2019_9986_MOESM2_ESM.tif (102 kb)
Supplementary material 2 (TIFF 101 kb)
12072_2019_9986_MOESM3_ESM.docx (14 kb)
Supplementary material 3 (DOCX 14 kb)


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Copyright information

© Asian Pacific Association for the Study of the Liver 2019

Authors and Affiliations

  • Manoj Kumar
    • 1
    Email author
  • Sumit Kainth
    • 1
  • Ashok Choudhury
    • 1
  • Rakhi Maiwall
    • 1
  • Lalita G. Mitra
    • 2
  • Vandana Saluja
    • 2
  • Prashant Mohan Agarwal
    • 2
  • Saggere Muralikrishna Shasthry
    • 1
  • Ankur Jindal
    • 1
  • Ankit Bhardwaj
    • 3
  • Guresh Kumar
    • 4
  • Shiv K. Sarin
    • 1
  1. 1.Department of HepatologyInstitute of Liver and Biliary SciencesNew DelhiIndia
  2. 2.Department of Critical Care MedicineInstitute of Liver and Biliary SciencesNew DelhiIndia
  3. 3.Department of Clinical ResearchInstitute of Liver and Biliary SciencesNew DelhiIndia
  4. 4.Department of BiostatisticsInstitute of Liver and Biliary SciencesNew DelhiIndia

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