Professor El-Omar has chosen Professors Belli, Duvoux, Adam, Fondevila and Polak, on behalf of the ELITA (European Liver and Intestine Association) and the European Liver Transplant Registry (ELTR) Board, to do the next #GUTBlog.

The #GUTBlog focusses on the latest paper “COVID-19 in liver transplant candidates: pretransplant and post-transplant outcomes – an ELITA/ELTR multicentre cohort study” which was published in paper copy in GUT in October 2021.

 

The Professors write:

“Concerns have been recently raised about the impact of COVID-19, the disease caused by SARS-CoV2, in subjects affected by cirrhosis, a term which describes a liver that has become firm and nodular as a response to different insults such as viral infections, disproportionate accumulation of fat or excessive alcohol intake. In Europe, almost 15,000 liver transplant (LT) candidates have been waiting for a new liver during the present COVID-19 pandemic, mainly for complications of cirrhosis such as accumulation of fluids in the abdominal cavity (ascites), impairment of mental functions (encephalopathy) and jaundice, or for hepatocellular carcinoma, the primary liver malignant tumour that typically develops in the setting of cirrhosis. As researchers and board members of the European Liver Transplant Association, ELITA, our goal that we perceived as our current primary mission, was to explore what would be the impact of COVID-19 on this fragile population, both in terms of mortality while on the waiting list and for those who recovered from COVID-19, in terms of outcome after transplantation.

To answer these questions, a comprehensive joint international initiative was put in place in early April 2020, during the dramatic COVID-19 first wave of the pandemic by ELITA, the European Liver Transplant Registry, ELTR, and the European Society for Organ Transplantation, ESOT. Using the ELTR network, our first step was to launch an online survey, which allowed us to identify 136 cases of COVID 19 from more than 2,220 LT candidates in 33 LT centres.  Then, as a second step, the same centres accepted to kindly provide us with more granular data which was collected in a dedicated common registry.

Several findings surprised us and deserve special attention. Firstly,the frequency of viral infection responsible for COVID-19 was 6%, which is double that observed in the general population of similar age; therefore, LT candidates seem highly susceptible to SARS-CoV-2 infection, unclear reasons yet remaining, and this finding underlines the crucial importance of the reinforced preventive measures of exposure to SARS-CoV-2 in these subjects. Secondly, the overall mortality risk at 2 months was 33% and sharply increased to 80% in patients with complications of cirrhosis and presenting with COVID-19 related shortness of breath. We were particularly struck by this observation, which clearly indicates that in LT candidates, COVID-19 is not only more frequent than in the general population, but also much more severe. This reminds us that patients listed for decompensated cirrhosis are particularly vulnerable and should be recognised among those at high risk of severe forms of COVID-19. Thirdly, respiratory failure was obviously a contraindication for proceeding with liver transplantation and accounted for the great majority of deaths, 89% suggesting that COVID-19 also threatened access to LT. Lastly, patients who recovered from COVID-19 acquired while on the waiting list, were transplanted after a median of 78 days with outcome after liver transplantation being extremely favourable, having a short-term survival of 96% and zero cases of COVID-19 recurrence to date.

On the whole, these results strongly indicate that huge efforts should be made to protect LT candidates from SARS-CoV-2, particularly those being listed for complications of cirrhosis. Unfortunately, data regarding response to COVID-19 vaccine in these subjects is scarce. The largest study from the Veteran Association (1), reports that the risks of COVID -19 infection and death are reduced by 50.3% and 100%, after the first dose of vaccine in patients having cirrhosis with complications. However, only 114 patients had cirrhosis with very advanced complications, a frequent condition in patients on the waiting list, for whom the protection given by the vaccine may be much lower.  In another study (2), response to vaccine was considered suboptimal in 25% of the cases, but only 10 patients had very advanced cirrhosis, suggesting that suboptimal response could be even more frequent among liver transplantation candidates. On this ground, ELITA is keen to propose implementing 3-dose vaccination protocols among LT candidates with advanced cirrhosis.

Opportunely, new therapeutic options such as monoclonal antibodies casirivimab/imdevimab which are able to prevent viral cell entry, have recently proved very effective when utilised in the early phase of the disease or even as a prophylactic in selected fragile populations (3), and are able to prevent the progression to more advanced stages in the majority of cases. According to ELITA, the use of these new drugs should be largely and quickly considered for this highly vulnerable population who waits for a life-saving procedure, the hope of which can be definitely threatened by SARS-CoV-2. The impact of these measures should be rapidly evaluated prospectively, the results of our study serving as a reference for the incidence and severity of COVID 19 in LT candidates.”

ELITA warmly thanks the participating ELTR centres for making the generation of this innovative data possible.

Professor LS Belli, Hepatologist, Niguarda Hospital, Milan

Professor C Duvoux, Hepatologist, Mondor Hospital, Paris

Professor R Adam, Transplant Surgeon and ELTR custodian, Paul-Brousse Hospital, Paris

Professor C Fondevila, Transplant Surgeon, La Paz Hospital, Madrid

Professor W Polak, Transplant Surgeon, Erasmus Medical Center, Rotterdam

on behalf of the ELITA Board

References:

1. Binu VJ,  Deng Y, Scheinberg A, et al.  Association of BNT162b2 mRNA and mRNA-1273 Vaccines With COVID-19 Infection and Hospitalization Among Patients With Cirrhosis. JAMA Internal Medicine 2021
2. Thuluvath PJ, Robarts P, Chauhan M et al. Analysis of antibody responses after COVID-19 vaccination in liver transplant recipients and those with chronic liver diseases. J Hepatol 2021;https://doi.org/10.1016/j.jhep.2021.08.008
3. Sidebottom DB and Gill D.Ronapreve for prophylaxis and treatment of Covid-19. BMJ2021; 374: n2136

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