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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

Abstract

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.

Methods

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).

Results

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.

Conclusions

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

NCT02583698.

Keywords

Acute-on-chronic liver failure Beta blockers Carvedilol 

Abbreviations

AARC

APASL ACLF Research Consortium

ACLF

Acute-on-chronic liver failure

AKI

Acute kidney injury

APASL

Asian Pacific Association for the Study of the Liver

CLIF-C

Chronic Liver Failure Consortium

DILI

Drug-induced liver injury

FHVP

Free hepatic venous pressure

HBV

Hepatitis B virus

HE

Hepatic encephalopathy

HEV

Hepatitis E virus

HVPG

Hepatic venous pressure gradient

INR

International normalized ratio

LT

Liver transplantation

NASH

Non-alcoholic steatohepatitis

NSBB

Non-selective beta blocker

WHVP

Wedged hepatic venous pressure

Notes

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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