Failure to Control Variceal Bleeding: Definition Matters.

We thank Baiges et al.[1]Baiges A. Bureau C. Garcia-Pagan J.C. Failure to control variceal bleeding: definition matters.J Hepatol. 2021; 74: 1491-1492Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar for their keen interest and observations regarding our study.[2]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: 66-79Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar 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]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: 66-79Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar 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. Baiges et al. raise several important questions.1.What is the role of transjugular intrahepatic portosystemic shunt (TIPS) in patients without acute-on-chronic liver failure (ACLF) with ‘failure to control bleeding’? We believe that our paper is underpowered to make any new conclusions about the role of rescue TIPS in patients with failure to control bleeding but without ACLF. As is the current clinical practice, these patients should be offered TIPS.2.How was ‘failure to control of bleeding’ controlled without TIPS? As a large proportion of our patients were referred from other centres, we found that many still had endoscopic options. Out of 174 patients in our study, further therapeutic endoscopy was successful in achieving satisfactory haemostasis in 82 (47.1%).3.Whether there is a sub-group in whom TIPS is futile? As reported in the paper[2]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: 66-79Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar and correctly observed by the Baiges[1]Baiges A. Bureau C. Garcia-Pagan J.C. Failure to control variceal bleeding: definition matters.J Hepatol. 2021; 74: 1491-1492Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar et al., none of the patients who had grade 2-3 ACLF “prior to the acute episode of variceal bleeding” survived, irrespective of their TIPS status. Of the patients who developed ACLF following an episode of variceal bleeding, all the survivors had a CLIF-C ACLF score of 62 or below. This confirms the previous futility cut-off in patients with ACLF for whom liver transplantation is not an option. Patients with a CLIF-C ACLF score of >64 after 48 hours of intensive care unit care are at high risk of death and those with a score of >70 almost invariably die irrespective of the aetiology or precipitant.[3]Engelmann C. Thomsen K. Zakeri N. Sheikh M. Agarwal B. Jalan R. et al.Validation of CLIF-C ACLF score to define a threshold for futility of intensive care support for patients with acute-on-chronic liver failure.Crit Care. 2018; 22: 254Crossref PubMed Scopus (54) Google Scholar Although these criteria provide a strong guide, futility of ongoing care needs to be decided on a case-by-case basis.4.Would preemptive TIPS (pTIPS) have prevented the need for rescue TIPS? The population studied was a highly selected patient group, most of whom were referred from other centres. It is extremely difficult to analyse this complex patient population in a retrospective study and come to any meaningful conclusion about whether pTIPS would have prevented the need for rescue TIPS. Despite high quality published data,[4]Garcia-Pagan J.C. Caca K. Bureau C. Laleman W. Appenrodt B. Luca A. et al.Early use of TIPS in patients with cirrhosis and variceal bleeding.N Engl J Med. 2010; 362: 2370-2379Crossref PubMed Scopus (801) Google Scholar,[5]Trebicka J. Gu W. Ibanez-Samaniego L. Hernandez-Gea V. Pitarch C. Garcia E. et al.Rebleeding and mortality risk are increased by ACLF but reduced by pre-emptive TIPS.J Hepatol. 2020; 73: 1082-1091Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar the role of pTIPS is still a matter of debate in the UK, which has been further fuelled by the recent negative trial from the Hayes group.[6]Dunne P.D.J. Sinha R. Stanley A.J. Lalchan N. Ireland H. Shams A. et al.Randomised clinical trial: standard of care versus early-transjugular intrahepatic porto-systemic shunt (TIPS) in patients with cirrhosis and oesophageal variceal bleeding.Aliment Pharmacol Ther. 2020; 52: 98-106Crossref PubMed Scopus (27) Google Scholar A large UK trial of pTIPS is in the process of being set up to definitively address this issue. The authors received no financial support to produce this manuscript. RK drafted the letter, RJ did the critical review Rajiv Jalan has research collaborations with Yaqrit and Takeda. Rajiv Jalan is the inventor of OPA, which has been patented by UCL and licensed to Mallinckrodt Pharma. He is also the founder of Yaqrit Ltd, a spin out company from University College London. He is also a Founder of Thoeris Ltd. Please refer to the accompanying ICMJE disclosure forms for further details. The following is the supplementary data to this article: Download .pdf (.26 MB) Help with pdf files Failure to control variceal bleeding: Definition mattersJournal of HepatologyVol. 74Issue 6PreviewAcute variceal bleeding (AVB) is recognized as a leading cause of mortality in patients with cirrhosis.1 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.2–5 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. Full-Text PDF Determinants of mortality in patients with cirrhosis and uncontrolled variceal bleedingJournal of HepatologyVol. 74Issue 1PreviewFailure 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. Full-Text PDF