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Letter to the Editor| Volume 74, ISSUE 6, P1491-1492, June 2021

Failure to control variceal bleeding: Definition matters

  • Author Footnotes
    † Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver).
    Anna Baiges
    Footnotes
    † Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver).
    Affiliations
    Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
    Search for articles by this author
  • Christophe Bureau
    Affiliations
    Toulouse Liver Unit, Hôpital Rangueil et CHU Toulouse et Paul Sabatier University, Toulouse3. 1 avenue Jean Poulhes, 31059 Toulouse cedex, France
    Search for articles by this author
  • Author Footnotes
    † Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver).
    Juan Carlos García-Pagán
    Correspondence
    Corresponding author. Address: Liver Unit, Hospital Clínic, Villarroel 170, Barcelona, Spain; Tel.: +34 93 2275400 (extension 3314).
    Footnotes
    † Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver).
    Affiliations
    Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
    Search for articles by this author
  • Author Footnotes
    † Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver).
Published:January 18, 2021DOI:https://doi.org/10.1016/j.jhep.2021.01.012
Failure to control variceal bleeding: Definition matters
Previous ArticleAcute liver failure
Next ArticleReply to: “Failure to control variceal bleeding: Definition matters”

      Linked Article

      • Determinants of mortality in patients with cirrhosis and uncontrolled variceal bleeding
        Journal of HepatologyVol. 74Issue 1
        • Preview
          Failure to control oesophago-gastric variceal bleeding (OGVB) and acute-on-chronic liver failure (ACLF) are both important prognostic factors in cirrhosis. The aims of this study were to determine whether ACLF and its severity define the risk of death in OGVB and whether insertion of rescue transjugular intrahepatic shunt (TIPS) improves survival in patients with failure to control OGVB and ACLF.
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      • Reply to: “Failure to control variceal bleeding: Definition matters”
        Journal of HepatologyVol. 74Issue 6
        • Preview
          We thank Baiges et al.1 for their keen interest and observations regarding our study.2 We completely agree that the definition of ‘failure to control bleeding’ is difficult to apply in individual clinical cases and in general its interpretation is dependent upon many factors including how sick the patients is, whether they have ongoing bleeding during an endoscopy session and the severity of bleeding. In our study,2 we defined ‘failure to control bleeding’ strictly as failure to achieve haemostasis despite 2 endoscopies or need for adjuncts such as Sengstaken-Blakemore tube (SBT) or a stent within 5 days of the first bleed in combination with vasoactive drugs.
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      To the Editor:
      Acute variceal bleeding (AVB) is recognized as a leading cause of mortality in patients with cirrhosis.
      • Reverter E.
      • Tandon P.
      • Augustin S.
      • Turon F.
      • Casu S.
      • Bastiampillai R.
      • et al.
      A MELD-based model to determine risk of mortality among patients with acute variceal bleeding.
      Gastroenterology. 2014; 146 (e3): 412-419https://doi.org/10.1053/j.gastro.2013.10.018
      Importantly, an episode of AVB comprises not only the risk of bleeding and re-bleeding but also the risk of triggering other complications, among which acute-on-chronic liver failure (ACLF) stands out.
      • Moreau R.
      • Jalan R.
      • Gines P.
      • Pavesi M.
      • Angeli P.
      • Cordoba J.
      • et al.
      Acute-on-Chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis.
      Gastroenterology. 2013; 144 (e9): 1426-1437https://doi.org/10.1053/j.gastro.2013.02.042
      , 
      • Jalan R.
      • Gines P.
      • Olson J.C.
      • Mookerjee R.P.
      • Moreau R.
      • Garcia-Tsao G.
      • et al.
      Acute-on chronic liver failure.
      J Hepatol. 2012; 57: 1336-1348https://doi.org/10.1016/j.jhep.2012.06.026
      , 
      • Garg H.
      • Kumar A.
      • Garg V.
      • Kumar M.
      • Kumar R.
      • Sharma B.C.
      • et al.
      Hepatic and systemic hemodynamic derangements predict early mortality and recovery in patients with acute-on-chronic liver failure.
      J Gastroenterol Hepatol. 2013; 28: 1361-1367https://doi.org/10.1111/jgh.12191
      , 
      • Trebicka J.
      Emergency TIPS in a Child-Pugh B patient: when does the window of opportunity open and close?.
      J Hepatol. 2017; 66: 442-450https://doi.org/10.1016/j.jhep.2016.10.025
      The term ACLF defines an abrupt worsening of hepatic and extrahepatic organ failure in patients with underlying liver disease. On the other side, transjugular intrahepatic portosystemic shunt (TIPS) is a highly effective tool to treat patients with portal hypertension and variceal bleeding, thus markedly reducing the risk of rebleeding, further liver decompensation and death. One of the main concerns regarding TIPS is its potential deleterious impact on patients with a markedly deteriorated liver function and ACLF, given that TIPS insertion could reduce hepatic perfusion and worsen liver function.
      In this setting, we read with great interest the study by Kumar et al. “Determinants of mortality in patients with cirrhosis and uncontrolled variceal bleeding”
      • Kumar R.
      • Kerbert A.J.C.
      • Sheikh M.F.
      • Roth N.
      • Calvao J.A.F.
      • Mesquita M.D.
      • et al.
      Determinants of mortality in patients with cirrhosis and uncontrolled variceal bleeding.
      J Hepatol. 2021; 74: 66-79https://doi.org/10.1016/j.jhep.2020.06.010
      that addresses the important issue of whether the insertion of a rescue TIPS in patients with failure to control AVB (with or without ACLF) improves survival. Kumar et al. evaluated data from 174 consecutive patients with failure to control AVB admitted to their intensive care unit; however, only 78 patients received TIPS and 104 were managed differently. The study published herein evaluated survival according to the presence or not of ACLF at the moment of TIPS placement, demonstrating that TIPS improved survival in patients with failure to control AVB and ACLF but not in those without ACLF.
      Despite the great implications of this study, its results should be interpreted carefully before extrapolating them to general practice. The study sends a confusing message as it seems to challenge the need for TIPS in patients with refractory bleeding. It is striking that, according to the authors’ results, TIPS insertion does not affect survival in patients without ACLF, thus calling into question the need to provide a definitive treatment with TIPS in patients with failure to control AVB. Most probably, the problem lies in the definition of “failure to control bleeding”. Refractory bleeding is usually defined as a variceal bleeding that does not respond to the combination of vasoactive drugs and endoscopic treatment. Nevertheless, the authors have expanded the notion to patients that still had endoscopic options, thus confusing the reader when stating that patients that did not undergo TIPS had a similar survival than those that did. Also, the authors do not detail the treatment applied in patients that did not undergo TIPS, which would undeniably have influenced survival. How was failure to control bleeding controlled without using TIPS?
      On another note, this study sets the perfect scenario to stablish the cut-off point and futility criteria for TIPS placement in patients with failure to control AVB. Although the authors show that the presence of grade 2-3 ACLF prior to the acute episode of variceal bleeding is an independent prognostic factor of mortality, unfortunately, they do not show whether there is a subgroup of patients with new-onset ACLF in whom TIPS may be futile. Also, it would have been interesting to see whether the different events triggering ACLF (infection, alcoholic hepatitis), or the presence of ACLF prior to bleeding, influence outcomes.
      Finally, it is worth mentioning that the authors do not detail the proportion of patients that would have fulfilled criteria for preemptive TIPS (pTIPS) before exhibiting failure to control AVB. Admittedly, and in spite of the overwhelming amount of data supporting the use of pTIPS, it is a fact that in the real-life setting the implementation of pTIPS is not as high as it should be.
      • Hernández-Gea V.
      • Procopet B.
      • Giráldez Á.
      • Amitrano L.
      • Villanueva C.
      • Thabut D.
      • et al.
      Preemptive-TIPS improves outcome in high-risk variceal bleeding: an observational study.
      Hepatology. 2018; (hep.30182)https://doi.org/10.1002/hep.30182
      ,
      • Nicoară-Farcău O.
      • Han G.
      • Rudler M.
      • Angrisani D.
      • Monescillo A.
      • Torres F.
      • et al.
      Effects of early placement of transjugular portosystemic shunts in patients with high-risk acute variceal bleeding: a meta-analysis of individual patient data.
      Gastroenterology. 2021; 160 (e10): 193-205https://doi.org/10.1053/j.gastro.2020.09.026
      Accordingly, the present study also shows the lack of implementation of pTIPS, which could justify the large number of patients reaching the point of requiring a rescue TIPS. Nevertheless, it would have been interesting to present these data (proportion of patients that would have fulfilled criteria for pTIPS) as a means of reinforcing the concept that, at least to some extent, the setting evaluated by the present study could have been avoided.

      Financial support

      JC García-Pagán received grants from Gore. Anna Baiges is recipient of a “Juan Rodes” fellowship grant from the Instituto de Salud Carlos III.

      Authors’ contributions

      A. Baiges, C. Bureau and JC. García-Pagán contributed to the letter concept and design as well as draft of the manuscript.

      Conflict of interest

      The authors declare no conflict of interest.
      Please refer to the accompanying ICMJE disclosure forms for further details.

      Supplementary data

      The following is the supplementary data to this article:

      References

        • Reverter E.
        • Tandon P.
        • Augustin S.
        • Turon F.
        • Casu S.
        • Bastiampillai R.
        • et al.
        A MELD-based model to determine risk of mortality among patients with acute variceal bleeding.
        Gastroenterology. 2014; 146 (e3): 412-419https://doi.org/10.1053/j.gastro.2013.10.018
        View in Article
        • Moreau R.
        • Jalan R.
        • Gines P.
        • Pavesi M.
        • Angeli P.
        • Cordoba J.
        • et al.
        Acute-on-Chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis.
        Gastroenterology. 2013; 144 (e9): 1426-1437https://doi.org/10.1053/j.gastro.2013.02.042
        View in Article
        • Jalan R.
        • Gines P.
        • Olson J.C.
        • Mookerjee R.P.
        • Moreau R.
        • Garcia-Tsao G.
        • et al.
        Acute-on chronic liver failure.
        J Hepatol. 2012; 57: 1336-1348https://doi.org/10.1016/j.jhep.2012.06.026
        View in Article
        • Garg H.
        • Kumar A.
        • Garg V.
        • Kumar M.
        • Kumar R.
        • Sharma B.C.
        • et al.
        Hepatic and systemic hemodynamic derangements predict early mortality and recovery in patients with acute-on-chronic liver failure.
        J Gastroenterol Hepatol. 2013; 28: 1361-1367https://doi.org/10.1111/jgh.12191
        View in Article
        • Trebicka J.
        Emergency TIPS in a Child-Pugh B patient: when does the window of opportunity open and close?.
        J Hepatol. 2017; 66: 442-450https://doi.org/10.1016/j.jhep.2016.10.025
        View in Article
        • Kumar R.
        • Kerbert A.J.C.
        • Sheikh M.F.
        • Roth N.
        • Calvao J.A.F.
        • Mesquita M.D.
        • et al.
        Determinants of mortality in patients with cirrhosis and uncontrolled variceal bleeding.
        J Hepatol. 2021; 74: 66-79https://doi.org/10.1016/j.jhep.2020.06.010
        View in Article
        • Hernández-Gea V.
        • Procopet B.
        • Giráldez Á.
        • Amitrano L.
        • Villanueva C.
        • Thabut D.
        • et al.
        Preemptive-TIPS improves outcome in high-risk variceal bleeding: an observational study.
        Hepatology. 2018; (hep.30182)https://doi.org/10.1002/hep.30182
        View in Article
        • Nicoară-Farcău O.
        • Han G.
        • Rudler M.
        • Angrisani D.
        • Monescillo A.
        • Torres F.
        • et al.
        Effects of early placement of transjugular portosystemic shunts in patients with high-risk acute variceal bleeding: a meta-analysis of individual patient data.
        Gastroenterology. 2021; 160 (e10): 193-205https://doi.org/10.1053/j.gastro.2020.09.026
        View in Article

      Article info

      Publication history

      Published online: January 18, 2021
      Accepted: January 11, 2021
      Received: January 5, 2021

      Identification

      DOI: https://doi.org/10.1016/j.jhep.2021.01.012

      Copyright

      © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

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