Thomas Sersté1, Alexia Cornillie2, Hassane Njimi3, Marco Pavesi4, Vicente Arroyo4, Antonella Putignano2, Laura Weichselbaum2, Pierre Deltenre2, Delphine Degré2, Eric Trépo5, Christophe Moreno5, Thierry Gustot6. 1. Liver Unit, Department of Gastroenterology and Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium; Department of Hepatogastroenterology, CHU Saint-Pierre, Bruxelles, Belgium. Electronic address: thomas.serste@skynet.be. 2. Liver Unit, Department of Gastroenterology and Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium. 3. Biomedical Statistics, Université Libre de Bruxelles, Bruxelles, Belgium. 4. The EASL-CLIF Consortium, European Foundation-CLIF, Barcelona, Spain. 5. Liver Unit, Department of Gastroenterology and Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium; Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Bruxelles, Belgium. 6. Liver Unit, Department of Gastroenterology and Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium; The EASL-CLIF Consortium, European Foundation-CLIF, Barcelona, Spain; Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Bruxelles, Belgium; Inserm Unité 1149, Centre de Recherche sur l'inflammation (CRI), Paris, France; UMR S_1149, Université Paris Diderot, Paris, France. Electronic address: thierry.gustot@erasme.ulb.ac.be.
Abstract
BACKGROUND & AIMS: A better identification of factors predicting death is needed in alcoholic hepatitis (AH). Acute-on-chronic liver failure (ACLF) occurs during the course of liver disease and can be identified when AH is diagnosed (prevalent ACLF [pACLF]) or during follow-up (incidental ACLF [iACLF]). This study analyzed the impact of ACLF on outcomes in AH and the role of infection on the onset of ACLF and death. METHODS: Patients admitted from July 2006 to July 2015 suffering from biopsy-proven severe (s)AH with a Maddrey discriminant function (mDF) ≥32 were included. Infectious episodes, ACLF, and mortality were assessed during a 168-day follow-up period. Results were validated on an independent cohort. RESULTS: One hundred sixty-five patients were included. Mean mDF was 66.3 ± 20.7 and mean model for end-stage liver disease score was 26.8 ± 7.4. The 28-day cumulative incidence of death (CID) was 31% (95% CI 24-39%). Seventy-nine patients (47.9%) had pACLF. The 28-day CID without pACLF and with pACLF-1, pACLF-2, and pACLF-3 were 10.4% (95% CI 5.1-18.0), 30.8% (95% CI 14.3-49.0), 58.3% (95% CI 35.6-75.5), and 72.4% (95% CI 51.3-85.5), respectively, p <0.0001. Twenty-nine patients (17.5%) developed iACLF. The 28-day relative risk of death in patients developing iACLF was 41.87 (95% CI 5.2-335.1; p <0.001). A previous infection was the only independent risk factor for developing iACLF during the follow-up. Prevalence, incidence, and impact on prognosis of ACLF were confirmed in a validation cohort of 97 patients with probable sAH. CONCLUSIONS: ACLF is frequent during the course of sAH and is associated with high mortality. Infection strongly predicts the development of ACLF in this setting. LAY SUMMARY: In patients with chronic liver disease, an acute deterioration of liver function combined with single or multiple organ failures is known as acute-on-chronic liver failure. This study shows that acute-on-chronic liver failure is frequent during the course of severe alcoholic hepatitis. In severe alcoholic hepatitis, acute-on-chronic liver failure is associated with high mortality and frequently occurs after an infection.
BACKGROUND & AIMS: A better identification of factors predicting death is needed in alcoholic hepatitis (AH). Acute-on-chronic liver failure (ACLF) occurs during the course of liver disease and can be identified when AH is diagnosed (prevalent ACLF [pACLF]) or during follow-up (incidental ACLF [iACLF]). This study analyzed the impact of ACLF on outcomes in AH and the role of infection on the onset of ACLF and death. METHODS:Patients admitted from July 2006 to July 2015 suffering from biopsy-proven severe (s)AH with a Maddrey discriminant function (mDF) ≥32 were included. Infectious episodes, ACLF, and mortality were assessed during a 168-day follow-up period. Results were validated on an independent cohort. RESULTS: One hundred sixty-five patients were included. Mean mDF was 66.3 ± 20.7 and mean model for end-stage liver disease score was 26.8 ± 7.4. The 28-day cumulative incidence of death (CID) was 31% (95% CI 24-39%). Seventy-nine patients (47.9%) had pACLF. The 28-day CID without pACLF and with pACLF-1, pACLF-2, and pACLF-3 were 10.4% (95% CI 5.1-18.0), 30.8% (95% CI 14.3-49.0), 58.3% (95% CI 35.6-75.5), and 72.4% (95% CI 51.3-85.5), respectively, p <0.0001. Twenty-nine patients (17.5%) developed iACLF. The 28-day relative risk of death in patients developing iACLF was 41.87 (95% CI 5.2-335.1; p <0.001). A previous infection was the only independent risk factor for developing iACLF during the follow-up. Prevalence, incidence, and impact on prognosis of ACLF were confirmed in a validation cohort of 97 patients with probable sAH. CONCLUSIONS: ACLF is frequent during the course of sAH and is associated with high mortality. Infection strongly predicts the development of ACLF in this setting. LAY SUMMARY: In patients with chronic liver disease, an acute deterioration of liver function combined with single or multiple organ failures is known as acute-on-chronic liver failure. This study shows that acute-on-chronic liver failure is frequent during the course of severe alcoholic hepatitis. In severe alcoholic hepatitis, acute-on-chronic liver failure is associated with high mortality and frequently occurs after an infection.
Authors: Kyle Lauren Poulsen; Megan R McMullen; Emily Huang; Christopher D Kibler; Megan M Sheehan; Lin Leng; Richard Bucala; Laura E Nagy Journal: Alcohol Clin Exp Res Date: 2019-05-14 Impact factor: 3.455
Authors: Matias A Avila; Jean-François Dufour; Alexander L Gerbes; Fabien Zoulim; Ramon Bataller; Patrizia Burra; Helena Cortez-Pinto; Bin Gao; Ian Gilmore; Philippe Mathurin; Christophe Moreno; Vladimir Poznyak; Bernd Schnabl; Gyongyi Szabo; Maja Thiele; Mark R Thursz Journal: Gut Date: 2019-12-26 Impact factor: 23.059