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 Toledo; Sebastian 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; International Club of Ascites Global Study Group

doi:10.1016/j.jhep.2020.07.046

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 Toledo

Sebastian 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^*, International Club of Ascites Global Study Group

^*Corresponding author for this work

University of Toronto
University of Padua
Postgraduate Institute of Medical Education and Research
University of Bologna
Institute of Liver and Biliary Sciences
University of Turin
University of Barcelona
August Pi i Sunyer Biomedical Research Institute
Centro de Investigación Biomédica en Red
European Foundation of Chronic Liver Failure (EF-Clif), Barcelona
Universidade Estadual de Campinas
Hallym University
Liver Unit, Hospital Dr. Carlos B. Udaondo, Buenos Aires, Argentina
Rosario University Medical School, Rosario, Argentina
Servico de Hepatologia do HRMS, Hospital Regional de Mato Grosso Do Sul- HRMS, Campo Grande, Brazil
University of Rome La Sapienza
University of Geneva
Autonomous University of Barcelona
University of Southern Denmark
Department of Gastroenterology, S.C.B. Medical College, Cuttack, India
Digestive Disease and Oncology Centre, Medistra Hospital, Jakarta, Indonesia
Universidad Austral de Chile
Hospital Italiano de Buenos Aires
Ghent University
University of Virginia
Tel Aviv Sourasky Medical Center
Pontificia Universidad Católica Argentina Santa María de los Buenos Aires - UCA
Soonchunhyang University
Ludwig Maximilian University of Munich
Hôpital Beaujon
Universidad de Chile
Friedrich Schiller University Jena
RWTH Aachen University
Inje University
Universidad Nacional de Asunción
Rutgers - The State University of New Jersey, Newark
Ewha Womans University
Korea University

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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 language	English
Pages (from-to)	330-339
Journal	Journal of hepatology
Volume	74
Issue number	2
DOIs	https://doi.org/10.1016/j.jhep.2020.07.046
Publication status	Published - 1 Feb 2021
Externally published	Yes

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1016/j.jhep.2020.07.046

Cite this

Wong, F., Piano, S., Singh, V., Bartoletti, M., Maiwall, R., Alessandria, C., Fernandez, J., Soares, E. C., Kim, D. J., Kim, S. E., Marino, M., Vorobioff, J., Barea, R. D. C. R., Merli, M., Elkrief, L., Vargas, V., Krag, A., Singh, S. P., Lesmana, L. A., ... International Club of Ascites Global Study Group (2021). Clinical features and evolution of bacterial infection-related acute-on-chronic liver failure. Journal of hepatology, 74(2), 330-339. https://doi.org/10.1016/j.jhep.2020.07.046

@article{a00047a4bf9c4707abfd66683e839e80,

title = "Clinical features and evolution of bacterial infection-related acute-on-chronic liver failure",

abstract = "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.",

author = "Florence Wong and Salvatore Piano and Virendra Singh and Michele Bartoletti and Rakhi Maiwall and Carlo Alessandria and Javier Fernandez and Soares, \{Elza Cotrim\} and Kim, \{Dong Joon\} and Kim, \{Sung Eun\} and Monica Marino and Julio Vorobioff and Barea, \{Rita de Cassia Ribeiro\} and Manuela Merli and Laure Elkrief and Victor Vargas and Aleksander Krag and Singh, \{Shivaram Prasad\} and Lesmana, \{Laurentius Adrianto\} and Claudio Toledo and Sebastian Marciano and Xavier Verhelst and Nicolas Intagliata and Liane Rabinowich and Luis Colombato and Kim, \{Sang Gyune\} and Alexander Gerbes and Francois Durand and Roblero, \{Juan Pablo\} and Tony Bruns and Yoon, \{Eileen Laurel\} and Marcos Girala and Pyrsopoulos, \{Nikolaos T.\} and Kim, \{Tae Hun\} and Yim, \{Sun Young\} and Adria Juanola and Adrian Gadano and Paolo Angeli and \{International Club of Ascites Global Study Group\} and Kalyan Bhamidimarri and Boyer, \{Thomas D.\} and Carlos Brodersen and Daniela Campion and Paolo Caraceni and \{de Man\}, \{Robert A.\} and Eduardo Fassio and Fialla, \{Annette Dam\} and Carmine Gambino and Vikas Gautam and Pere Gines and Hwang, \{Jae Seok\} and Kim, \{Hyoung Su\} and Kim, \{Jeong Han\} and Pramod Kumar and Barbara Lattanz and Lee, \{Tae Hee\} and \{Rinaldi Lesmana\}, \{Cosmas A.\} and Marina Maevskaya and Preetam Nath and Gustavo Navarro and Ji-Won Park and Gisela Pinero and Sophie Restellini and Gustavo Romero and \{Sev{\'a} -Pereira\}, Tiago and Macarena Sim{\'o}n-Talero and Song, \{Do Seon\} and Suk, \{Ki Tae\} and \{van Vlierberghe\}, Hans and Giacomo Zaccherini",

year = "2021",

month = feb,

day = "1",

doi = "10.1016/j.jhep.2020.07.046",

language = "English",

volume = "74",

pages = "330--339",

journal = "Journal of hepatology",

issn = "0168-8278",

publisher = "Elsevier",

number = "2",

}

Wong, F, Piano, S, Singh, V, Bartoletti, M, Maiwall, R, Alessandria, C, Fernandez, J, Soares, EC, Kim, DJ, Kim, SE, Marino, M, Vorobioff, J, Barea, RDCR, Merli, M, Elkrief, L, Vargas, V, Krag, A, Singh, SP, Lesmana, LA, Toledo, C, Marciano, S, Verhelst, X, Intagliata, N, Rabinowich, L, Colombato, L, Kim, SG, Gerbes, A, Durand, F, Roblero, JP, Bruns, T, Yoon, EL, Girala, M, Pyrsopoulos, NT, Kim, TH, Yim, SY, Juanola, A, Gadano, A, Angeli, P & International Club of Ascites Global Study Group 2021, 'Clinical features and evolution of bacterial infection-related acute-on-chronic liver failure', Journal of hepatology, vol. 74, no. 2, pp. 330-339. https://doi.org/10.1016/j.jhep.2020.07.046

TY - JOUR

T1 - Clinical features and evolution of bacterial infection-related acute-on-chronic liver failure

AU - Wong, Florence

AU - Piano, Salvatore

AU - Singh, Virendra

AU - Bartoletti, Michele

AU - Maiwall, Rakhi

AU - Alessandria, Carlo

AU - Fernandez, Javier

AU - Soares, Elza Cotrim

AU - Kim, Dong Joon

AU - Kim, Sung Eun

AU - Marino, Monica

AU - Vorobioff, Julio

AU - Barea, Rita de Cassia Ribeiro

AU - Merli, Manuela

AU - Elkrief, Laure

AU - Vargas, Victor

AU - Krag, Aleksander

AU - Singh, Shivaram Prasad

AU - Lesmana, Laurentius Adrianto

AU - Toledo, Claudio

AU - Marciano, Sebastian

AU - Verhelst, Xavier

AU - Intagliata, Nicolas

AU - Rabinowich, Liane

AU - Colombato, Luis

AU - Kim, Sang Gyune

AU - Gerbes, Alexander

AU - Durand, Francois

AU - Roblero, Juan Pablo

AU - Bruns, Tony

AU - Yoon, Eileen Laurel

AU - Girala, Marcos

AU - Pyrsopoulos, Nikolaos T.

AU - Kim, Tae Hun

AU - Yim, Sun Young

AU - Juanola, Adria

AU - Gadano, Adrian

AU - Angeli, Paolo

AU - International Club of Ascites Global Study Group

AU - Bhamidimarri, Kalyan

AU - Boyer, Thomas D.

AU - Brodersen, Carlos

AU - Campion, Daniela

AU - Caraceni, Paolo

AU - de Man, Robert A.

AU - Fassio, Eduardo

AU - Fialla, Annette Dam

AU - Gambino, Carmine

AU - Gautam, Vikas

AU - Gines, Pere

AU - Hwang, Jae Seok

AU - Kim, Hyoung Su

AU - Kim, Jeong Han

AU - Kumar, Pramod

AU - Lattanz, Barbara

AU - Lee, Tae Hee

AU - Rinaldi Lesmana, Cosmas A.

AU - Maevskaya, Marina

AU - Nath, Preetam

AU - Navarro, Gustavo

AU - Park, Ji-Won

AU - Pinero, Gisela

AU - Restellini, Sophie

AU - Romero, Gustavo

AU - Sevá -Pereira, Tiago

AU - Simón-Talero, Macarena

AU - Song, Do Seon

AU - Suk, Ki Tae

AU - van Vlierberghe, Hans

AU - Zaccherini, Giacomo

PY - 2021/2/1

Y1 - 2021/2/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85096540974

UR - https://www.ncbi.nlm.nih.gov/pubmed/32781201

U2 - 10.1016/j.jhep.2020.07.046

DO - 10.1016/j.jhep.2020.07.046

M3 - Article

C2 - 32781201

SN - 0168-8278

VL - 74

SP - 330

EP - 339

JO - Journal of hepatology

JF - Journal of hepatology

IS - 2

ER -

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

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