Clinical features and evolution of bacterial infection-related acute-on-chronic liver failure

Florence Wong, Salvatore Piano, Virendra Singh, Michele Bartoletti, Rakhi Maiwall, Carlo Alessandria, Javier Fernandez, Elza Cotrim Soares, Dong Joon Kim, Sung Eun Kim, Monica Marino, Julio Vorobioff, Rita de Cassia Ribeiro Barea, Manuela Merli, Laure Elkrief, Victor Vargas, Aleksander Krag, Shivaram Prasad Singh, Laurentius Adrianto Lesmana, Claudio ToledoSebastian Marciano, Xavier Verhelst, Nicolas Intagliata, Liane Rabinowich, Luis Colombato, Sang Gyune Kim, Alexander Gerbes, Francois Durand, Juan Pablo Roblero, Tony Bruns, Eileen Laurel Yoon, Marcos Girala, Nikolaos T. Pyrsopoulos, Tae Hun Kim, Sun Young Yim, Adria Juanola, Adrian Gadano, Paolo Angeli, Kalyan Bhamidimarri, Thomas D. Boyer, Carlos Brodersen, Daniela Campion, Paolo Caraceni, Robert A. de Man, Eduardo Fassio, Annette Dam Fialla, Carmine Gambino, Vikas Gautam, Pere Gines, Jae Seok Hwang, Hyoung Su Kim, Jeong Han Kim, Pramod Kumar, Barbara Lattanz, Tae Hee Lee, Cosmas A. Rinaldi Lesmana, Marina Maevskaya, Preetam Nath, Gustavo Navarro, Ji Won Park, Gisela Pinero, Sophie Restellini, Gustavo Romero, Tiago Sevá -Pereira, Macarena Simón-Talero, Do Seon Song, Ki Tae Suk, Hans Van Vlierberghe, Giacomo Zaccherini

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Background & Aims: Bacterial infections can trigger the development of organ failure(s) and acute-on-chronic liver failure (ACLF). Geographic variations in bacteriology and clinical practice could lead to worldwide differences in ACLF epidemiology, phenotypes and associated outcomes. Herein, we aimed to evaluate regional differences in bacterial infection-related ACLF in patients with cirrhosis admitted to hospital. Methods: This post hoc analysis included 1,175 patients with decompensated cirrhosis (with bacterial infection on admission or nosocomial infection) from 6 geographic regions worldwide. Clinical, laboratory and microbiological data were collected from the diagnosis of infection. Patients were followed-up for organ failure(s) and ACLF development according to the EASL-CLIF criteria from enrolment to discharge/death. Results: A total of 333 patients (28%) had ACLF at diagnosis of infection, while 230 patients developed ACLF after diagnosis of infection, resulting in an overall rate of bacterial infection related-ACLF of 48%, with rates differing amongst different geographic regions (38% in Southern Europe vs. 75% in the Indian subcontinent). Bacterial infection related-ACLF more frequently developed in younger patients (55 ± 13 vs. 58 ± 14 years), males (73% vs. 62%), patients with alcohol-related cirrhosis (59% vs. 45%) and those with a higher baseline MELD score (25 ± 11 vs. 16 ± 5) (all p <0.001). Spontaneous bacterial peritonitis, pneumonia or infections caused by extensively drug resistant (XDR) bacteria were more frequently associated with ACLF development. More patients with ACLF had a positive quick sequential organ failure assessment score and septic shock, resulting in a lower infection resolution rate (all p <0.001). Conclusions: Bacterial infections, especially with XDR organisms, are associated with the highest risk of ACLF development, accounting for almost half of cases globally. Geographic differences result in variable epidemiology and clinical outcomes. Lay summary: Bacterial infections can trigger a sudden deterioration in an otherwise stable cirrhotic patient, a condition known as acute-on-chronic liver failure or ACLF. This study has found that the development of ACLF following bacterial infection occurs most commonly in the Indian subcontinent and less so in Southern Europe. The common infections that can trigger ACLF include infection of the abdominal fluid, known as spontaneous bacterial peritonitis, pneumonia and by bacteria that are resistant to multiple antibiotics. Patients who develop ACLF following a bacterial infection have high death rates and are frequently unable to clear the infection.

Original languageEnglish
JournalJournal of Hepatology
Publication statusAccepted/In press - 2020


  • ACLF
  • Antibiotic resistance
  • Cirrhosis
  • Liver transplantation
  • MDR
  • Sepsis
  • XDR

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