PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis

Trebicka, J.; Fernandez, J.; Papp, M.; Caraceni, P.; Laleman, W.; Gambino, C.; Giovo, I.; Uschner, F. E.; Jansen, C.; Jimenez, C.; Mookerjee, R.; Gustot, T.; Albillos, A.; Banares, R.; Jarcuska, P.; Steib, C.; Reiberger, T.; Acevedo, J.; Gatti, P.; Shawcross, D. L.; Zeuzem, S.; Zipprich, A.; Piano, S.; Berg, T.; Bruns, T.; Danielsen, K. V.; Coenraad, M.; Merli, M.; Stauber, R.; Zoller, H.; Ramos, J. P.; Sole, C.; Soriano, G.; de Gottardi, A.; Gronbaek, H.; Saliba, F.; Trautwein, C.; Kani, H. T.; Francque, S.; Ryder, S.; Nahon, P.; Romero-Gomez, M.; Van Vlierberghe, H.; Francoz, C.; Manns, M.; Garcia-Lopez, E.; Tufoni, M.; Amoros, A.; Pavesi, M.; Sanchez, C.; Praktiknjo, M.; Curto, A.; Pitarch, C.; Putignano, A.; Moreno, E.; Bernal, W.; Aguilar, F.; Claria, J.; Ponzo, P.; Vitalis, Z.; Zaccherini, G.; Balogh, B.; Gerbes, A.; Vargas, V.; Alessandria, C.; Bernardi, M.; Gines, P.; Moreau, R.; Angeli, P.; Jalan, R.; Arroyo, V.; Maschmeier, M.; Semela, D.; Elkrief, L.; Elsharkawy, A.; Tornai, T.; Tornai, I.; Altorjay, I.; Antognoli, A.; Baldassarre, M.; Gagliardi, M.; Bertoli, E.; Mareso, S.; Brocca, A.; Campion, D.; Saracco, G. M.; Rizzo, M.; Lehmann, J.; Pohlmann, A.; Brol, M. J.; Chang, J.; Schierwagen, R.; Sola, E.; Amari, N.; Rodriguez, M.; Nevens, F.; Clemente, A.; Janicko, M.; Markwardt, D.; Mandorfer, M.; Welsch, C.; Welzel, T. M.; Ciraci, E.; Patel, V.; Ripoll, C.; Herber, A.; Horn, P.; Bendtsen, F.; Gluud, L. L.; Schaapman, J.; Riggio, O.; Rainer, F.; Moritz, J. T.; Mesquita, M.; Alvarado-Tapias, E.; Akpata, O.; Aamann, L.; Samuel, D.; Tresson, S.; Strnad, P.; Amathieu, R.; Simon-Talero, M.; Smits, F.; van den Ende, N.; Martinez, J.; Garcia, R.; Rupprechter, H.; Engelmann, C.; Ozdogan, O. C.

doi:10.1016/j.jhep.2020.11.019

Background & Aims: Acute decompensation (AD) of cirrhosis may present without acute-on-chronic liver failure (ACLF) (AD-No ACLF), or with ACLF (AD-ACLF), defined by organ failure(s). Herein, we aimed to analyze and characterize the precipitants leading to both of these AD phenotypes. Methods: The multicenter, prospective, observational PREDICT study (NCT03056612) included 1,273 non-electively hospitalized patients with AD (No ACLF = 1,071; ACLF = 202). Medical history, clinical data and laboratory data were collected at enrolment and during 90-day follow-up, with particular attention given to the following characteristics of precipitants: induction of organ dysfunction or failure, systemic inflammation, chronology, intensity, and relationship to outcome. Results: Among various clinical events, 4 distinct events were precipitants consistently related to AD: proven bacterial infections, severe alcoholic hepatitis, gastrointestinal bleeding with shock and toxic encephalopathy. Among patients with precipitants in the AD-No ACLF cohort and the AD-ACLF cohort (38% and 71%, respectively), almost all (96% and 97%, respectively) showed proven bacterial infection and severe alcoholic hepatitis, either alone or in combination with other events. Survival was similar in patients with proven bacterial infections or severe alcoholic hepatitis in both AD phenotypes. The number of precipitants was associated with significantly increased 90-day mortality and was paralleled by increasing levels of surrogates for systemic inflammation. Importantly, adequate first-line antibiotic treatment of proven bacterial infections was associated with a lower ACLF development rate and lower 90-day mortality. Conclusions: This study identified precipitants that are significantly associated with a distinct clinical course and prognosis in patients with AD. Specific preventive and therapeutic strategies targeting these events may improve outcomes in patients with decompensated cirrhosis. Lay summary: Acute decompensation (AD) of cirrhosis is characterized by a rapid deterioration in patient health. Herein, we aimed to analyze the precipitating events that cause AD in patients with cirrhosis. Proven bacterial infections and severe alcoholic hepatitis, either alone or in combination, accounted for almost all (96-97%) cases of AD and acute-on-chronic liver failure. Whilst the type of precipitant was not associated with mortality, the number of precipitant(s) was. This study identified precipitants that are significantly associated with a distinct clinical course and prognosis of patients with AD. Specific preventive and therapeutic strategies targeting these events may improve patient outcomes.