Eleonora De Martin1, Audrey Coilly2, Olivier Chazouillères3, Olivier Roux4, Jean-Marie Peron5, Pauline Houssel-Debry6, Florent Artru7, Christine Silvain8, Isabelle Ollivier-Hourmand9, Christophe Duvoux10, Alexandra Heurgue11, Sandrine Barge12, Nathalie Ganne-Carrié13, Georges-Philippe Pageaux14, Camille Besch15, Marc Bourlière16, Hélène Fontaine17, Victor de Ledinghen18, Jérôme Dumortier19, Filomena Conti20, Sylvie Radenne21, Marilyne Debette-Gratien22, Odile Goria23, François Durand4, Pascal Potier24, Vincent Di Martino25, Noemi Reboux26, Philippe Ichai2, Mylène Sebagh27, Philippe Mathurin7, Hélène Agostini28, Didier Samuel2, Jean-Charles Duclos-Vallée29. 1. AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Inserm Unité 1193, Université Paris-Saclay, FHU Hépatinov, Centre de Référence Maladies Inflammatoires des Voies Biliaires et Hépatites Auto-immunes, Villejuif, France. Electronic address: eleonora.demartin@aphp.fr. 2. AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Inserm Unité 1193, Université Paris-Saclay, FHU Hépatinov, Centre de Référence Maladies Inflammatoires des Voies Biliaires et Hépatites Auto-immunes, Villejuif, France. 3. AP-HP Hôpital St Antoine, Université Pierre et Marie Curie Paris 6, Centre de Référence Maladies Inflammatoires des Voies Biliaires et Hépatites Auto-immunes, Service d'Hépato-Gastroentérologie, Paris, France. 4. AP-HP Hôpital Beaujon, Centre de Références des Maladies Vasculaires du Foie, Service d'Hépatologie, Clichy, France. 5. Service d'Hépatologie, Hôpital Rangueil CHU Toulouse, Université Paul Sabatier III, Toulouse, France. 6. CHU de Rennes, Hôpital Pontchaillou, Service d'Hépatologie et Transplantation Hépatique, Rennes, France. 7. CHRU Lille, Hôpital Claude Huriez, Service des Maladies de l'Appareil Digestif, Lille, France. 8. CHU Poitiers, Service Hépato-Gastro-Entérologie, Poitiers, France. 9. CHU Caen, Service Hépato-Gastro-Entérologie et Nutrition, Caen, France. 10. AP-HP Hôpital Henri-Mondor, Service d'Hépato-Gastroentérologie, Créteil, France. 11. CHU Reims Service Hépato-Gastro-Entérologie et Cancérologie Digestive, Reims, France. 12. Hôpital Saint Camille, Service Hépato-Gastro-entérologie, Bry-sur-Marne, France. 13. AP-HP Hôpital Jean Verdier, Service d'Hépatologie, Bondy, France. 14. CHU Saint-Eloi, Département d'Hépato-Gastroentérologie et de Transplantation Hépatique, Montpellier, France. 15. Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre, Service de Chirurgie Générale, Hépatique, Endocrinienne et Transplantation, Strasbourg, France. 16. Hôpital St Joseph, Service d'Hépato-Gastroentérologie, Marseille, France. 17. AP-HP CHU Cochin, Service d'Hépatologie, Université Paris Descartes, INSERM U-818 et USM20, Institut Pasteur, Paris, France. 18. CHU Haut-Lévêque, Service d'Hépato-Gastroentérologie, Bordeaux, France. 19. Hospices Civils de Lyon, Hôpital édouard Herriot, Fédération des Spécialités Digestives, et Université de Lyon, Lyon, France. 20. AP-HP Hôpital de la Pitié Salpêtrière, Service de Transplantation Hépatique, Paris, France. 21. Hospices Civils de Lyon, Hôpital de la Croix-Rousse, Service d'Hépato-Gastroentérologie, Lyon, France. 22. CHU de Limoges, Service d'Hépato-Gastroentérologie, 87042 Limoges, France. 23. CHU Rouen, Service d'Hépato-gastroentérologie, Rouen, France. 24. CHR d'Orléans, Service d'Hépato-Gastro-entérologie et Oncologie Digestive, Orléans, France. 25. CHRU Jean Minjoz, Service d'Hépatologie, Besançon, France. 26. Hôpital La Cavale Blanche, Service d'Hépato-Gastroentérologie, Brest, France. 27. AP-HP Hôpital du Kremlin-Bicêtre, Service Anatomie et Cytologie Pathologiques, Le Kremlin-Bicêtre, France. 28. AP-HP Paris Saclay, Unité de Recherche Clinique des Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, France. 29. AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Inserm Unité 1193, Université Paris-Saclay, FHU Hépatinov, Centre de Référence Maladies Inflammatoires des Voies Biliaires et Hépatites Auto-immunes, Villejuif, France. Electronic address: jean-charles.duclos-vallee@aphp.fr.
Abstract
BACKGROUND & AIMS: In acute severe autoimmune hepatitis (AS-AIH), the optimal timing for liver transplantation (LT) remains controversial. The objectives of this study were to determine early predictive factors for a non-response to corticosteroids and to propose a score to identify patients in whom LT is urgently indicated. METHODS: This was a retrospective, multicenter study (2009-2016). A diagnosis of AS-AIH was based on: i) Definite or probable AIH based on the simplified IAIHG score; ii) international normalized ratio (INR) ≥1.5 and/or bilirubin >200 μmol/L; iii) No previous history of AIH; iv) Histologically proven AIH. A treatment response was defined as LT-free survival at 90 days. The evolution of variables from corticosteroid initiation (day-D0) to D3 was estimated from: Δ%3 = (D3-D0)/D0. RESULTS: A total of 128 patients were included, with a median age of 52 (39-62) years; 72% were female. Overall survival reached 88%. One hundred and fifteen (90%) patients received corticosteroids, with a LT-free survival rate of 66% at 90 days. Under multivariate analysis, D0-INR (odds ratio [OR] 6.85; 95% CI 2.23-21.06; p <0.001), Δ%3-INR ≥0.1% (OR 6.97; 95% CI 1.59-30.46; p <0.01) and Δ%3-bilirubin ≥-8% (OR 5.14; 95% CI 1.09-24.28; p <0.04) were predictive of a non-response. The SURFASA score: -6.80+1.92∗(D0-INR)+1.94∗(Δ%3-INR)+1.64∗(Δ%3-bilirubin), created by combining these variables, was highly predictive of LT or death (AUC = 0.93) (88% specificity; 84% sensitivity) with a cut-off point of <-0.9. Below this cut-off, the chance of responding was 75%. With a score higher than 1.75, the risk of dying or being transplanted was between 85% and 100%. CONCLUSION: In patients with AS-AIH, INR at the introduction of corticosteroids and the evolution of INR and bilirubin are predictive of LT or death. Within 3 days of initiating corticosteroids, the SURFASA score can identify non-responders who require a referral for LT. This score needs to be validated in a prospective cohort. LAY SUMMARY: The management of patients with acute severe autoimmune hepatitis is highly challenging, particularly regarding their early referral for liver transplantation. We found that international normalized ratio at the initiation of corticosteroid therapy and the evolution of international normalized ratio and bilirubin values after 3 days of therapy were highly predictive of liver transplantation or death. We are thus proposing a score that combines these variables and identifies patients in whom liver transplantation is urgently required.
BACKGROUND & AIMS: In acute severe autoimmune hepatitis (AS-AIH), the optimal timing for liver transplantation (LT) remains controversial. The objectives of this study were to determine early predictive factors for a non-response to corticosteroids and to propose a score to identify patients in whom LT is urgently indicated. METHODS: This was a retrospective, multicenter study (2009-2016). A diagnosis of AS-AIH was based on: i) Definite or probable AIH based on the simplified IAIHG score; ii) international normalized ratio (INR) ≥1.5 and/or bilirubin >200 μmol/L; iii) No previous history of AIH; iv) Histologically proven AIH. A treatment response was defined as LT-free survival at 90 days. The evolution of variables from corticosteroid initiation (day-D0) to D3 was estimated from: Δ%3 = (D3-D0)/D0. RESULTS: A total of 128 patients were included, with a median age of 52 (39-62) years; 72% were female. Overall survival reached 88%. One hundred and fifteen (90%) patients received corticosteroids, with a LT-free survival rate of 66% at 90 days. Under multivariate analysis, D0-INR (odds ratio [OR] 6.85; 95% CI 2.23-21.06; p <0.001), Δ%3-INR ≥0.1% (OR 6.97; 95% CI 1.59-30.46; p <0.01) and Δ%3-bilirubin ≥-8% (OR 5.14; 95% CI 1.09-24.28; p <0.04) were predictive of a non-response. The SURFASA score: -6.80+1.92∗(D0-INR)+1.94∗(Δ%3-INR)+1.64∗(Δ%3-bilirubin), created by combining these variables, was highly predictive of LT or death (AUC = 0.93) (88% specificity; 84% sensitivity) with a cut-off point of <-0.9. Below this cut-off, the chance of responding was 75%. With a score higher than 1.75, the risk of dying or being transplanted was between 85% and 100%. CONCLUSION: In patients with AS-AIH, INR at the introduction of corticosteroids and the evolution of INR and bilirubin are predictive of LT or death. Within 3 days of initiating corticosteroids, the SURFASA score can identify non-responders who require a referral for LT. This score needs to be validated in a prospective cohort. LAY SUMMARY: The management of patients with acute severe autoimmune hepatitis is highly challenging, particularly regarding their early referral for liver transplantation. We found that international normalized ratio at the initiation of corticosteroid therapy and the evolution of international normalized ratio and bilirubin values after 3 days of therapy were highly predictive of liver transplantation or death. We are thus proposing a score that combines these variables and identifies patients in whom liver transplantation is urgently required.
Authors: Luis Téllez; Eugenia Sánchez Rodríguez; Enrique Rodríguez de Santiago; Laura Llovet; Ana Gómez-Outomuro; Fernando Díaz-Fontenla; Patricia Álvarez López; María García-Eliz; Carla Amaral; Yolanda Sánchez-Torrijos; José Ignacio Fortea; Carlos Ferre-Aracil; Manuel Rodríguez-Perálvarez; Marta Abadía; Judith Gómez-Camarero; Antonio Olveira; José Luis Calleja; Javier Crespo; Manuel Romero; Manuel Hernández-Guerra; Marina Berenguer; Mar Riveiro-Barciela; Magdalena Salcedo; Manuel Rodríguez; María Carlota Londoño; Agustín Albillos Journal: Aliment Pharmacol Ther Date: 2022-04-25 Impact factor: 9.524