Liver transplantation for patients with acute-on-chronic liver failure (ACLF) in Europe: Results of the ELITA/EF-CLIF collaborative study (ECLIS)

Belli, L. S.; Duvoux, C.; Artzner, T.; Bernal, W.; Conti, S.; Cortesi, P. A.; Sacleux, S. -C.; Pageaux, G. -P.; Radenne, S.; Trebicka, J.; Fernandez, J.; Perricone, G.; Piano, S.; Nadalin, S.; Morelli, M. C.; Martini, S.; Polak, W. G.; Zieniewicz, K.; Toso, C.; Berenguer, M.; Iegri, C.; Invernizzi, F.; Volpes, R.; Karam, V.; Adam, R.; Faitot, F.; Rabinovich, L.; Saliba, F.; Meunier, L.; Lesurtel, M.; Uschner, F. E.; Fondevila, C.; Michard, B.; Coilly, A.; Meszaros, M.; Poinsot, D.; Schnitzbauer, A.; De Carlis, L. G.; Fumagalli, R.; Angeli, P.; Arroyo, V.; Jalan, R.; Vigano, R.; Mazzarelli, C.; Lauterio, A.; Giacomoni, A.; Donato, F.; Lampertico, P.; Pasulo, L.; Fagiuoli, S.; Colledan, M.; Morelli, M. C.; Vitale, G.; Patrono, D.; Romagnoli, R.; Ottobrelli, A.; Petridis, I.; Cillo, U.; Germani, G.; Burra, P.; Bachellier, P.; Addeo, P.; Besch, C.; Faitot, F.; Sacleux, S. C.; Faouzi, S.; Adam, R.; Samuel, D.; Guichon, C.; Faure, S.; Ursic-Bedoya, J.; Colmenero, J.; Toapanta, D.; Hernandez-Tejero, M.; Vinaixa, C.; Hoed, C. D.; de Haan, J. E.; Della Penna, A.; Uschner, F. E.; Welker, M.; Zeuzem, S.; Bechstein, W.; Goossens, N.; Raszeja-Wyszomirska, J.; Katarey, D.; Agarwal, B.

doi:10.1016/j.jhep.2021.03.030

Background & Aims: Liver transplantation (LT) has been proposed as an effective salvage therapy even for the sickest patients with acute-on-chronic liver failure (ACLF). This large collaborative study was designed to assess the current clinical practice and outcomes of patients with ACLF who are wait-listed for LT in Europe. Methods: This was a retrospective study including 308 consecutive patients with ACLF, listed in 20 centres across 8 European countries, from January 2018 to June 2019. Results: A total of 2,677 patients received a LT: 1,216 (45.4%) for decompensated cirrhosis. Of these, 234 (19.2%) had ACLF at LT: 58 (4.8%) had ACLF-1, 78 (6.4%) had ACLF-2, and 98 (8.1%) had ACLF-3. Wide variations were observed amongst countries: France and Germany had high rates of ACLF-2/3 (27–41%); Italy, Switzerland, Poland and the Netherlands had medium rates (9–15%); and the United Kingdom and Spain had low rates (3–5%) (p <0.0001). The 1-year probability of survival after LT for patients with ACLF was 81% (95% CI 74–87). Pre-LT arterial lactate levels >4 mmol/L (hazard ratio [HR] 3.14; 95% CI 1.37–7.19), recent infection from multidrug resistant organisms (HR 3.67; 95% CI 1.63–8.28), and renal replacement therapy (HR 2.74; 95% CI 1.37–5.51) were independent predictors of post-LT mortality. During the same period, 74 patients with ACLF died on the waiting list. In an intention-to-treat analysis, 1-year survival of patients with ACLF on the LT waiting list was 73% for ACLF-1 or -2 and 50% for ACLF-3. Conclusion: The results reveal wide variations in the listing of patients with ACLF in Europe despite favourable post-LT survival. Risk factors for mortality were identified, enabling a more precise prognostic assessment of patients with ACLF. Lay summary: Acute-on-chronic liver failure (ACLF) is a severe clinical condition for which liver transplantation is an effective therapeutic option. This study has demonstrated that in Europe, referral and access to liver transplantation (LT) for patients with ACLF needs to be harmonised to avoid inequities. Post-LT survival for patients with ACLF was >80% after 1 year and some factors have been identified to help select patients with favourable outcomes.