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

Published:August 08, 2020DOI:https://doi.org/10.1016/j.jhep.2020.07.046

      Highlights

      • Among patients with cirrhosis and bacterial infections, 48% have bacterial infection related-ACLF.
      • ACLF following bacterial infection occurs most commonly in the Indian subcontinent and less so in Southern Europe.
      • ACLF occurs more frequently following spontaneous bacterial peritonitis, pneumonia, and nosocomial infections.
      • Patients with ACLF have lower infection resolution rate and higher mortality rate.

      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.

      Graphical abstract

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      Linked Article

      • Bacterial infection-related acute-on-chronic liver failure: The standpoint matters!
        Journal of HepatologyVol. 75Issue 4
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          We read with great interest the article by Wong and Piano et al.1 regarding the differences among the geographic areas in the development and outcomes of bacterial infection triggered acute-on-chronic liver failure (ACLF). The study highlighted a higher rate and severity of bacterial infection-triggered ACLF in the Indian subcontinent than in Europe and America. The authors also demonstrated a higher incidence of multidrug-resistant (MDR) bacterial infection-related ACLF, leading to a worse outcome in the Asian population.
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          With great interest, we read the study of Wong et al. who investigated risk factors for an acute-on-chronic liver failure (ACLF) in patients with decompensated cirrhosis and bacterial infections. Spontaneous bacterial peritonitis (SBP) was the most frequent site of infection and an independent risk factor for ACLF development. Moreover, ACLF was more common in patients infected with multidrug resistant bacteria (MDRB) and those with an insufficient response to the initial antibiotic treatment.1 Their study once more underlines the critical role of fast and adequate antibiotic treatment in patients with decompensated cirrhosis.
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      • Characterizing bacterial infections in acute-on-chronic liver failure among patients with cirrhosis from nonalcoholic steatohepatitis
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          I read with great interest the study by Wong and Piano et al.1 In the United States, non-alcoholic fatty liver disease (NAFLD)-related acute-on-chronic liver failure (ACLF) is the second leading cause of transplant listing, while listings for NAFLD-ACLF are outpacing listings for NAFLD without ACLF.2 This is particularly noteworthy, since unlike other etiologies of liver disease associated with ACLF, namely alcohol-related liver disease and HBV infection, NAFLD is a disease process without an inherent precipitant such as alcohol use or flare of hepatitis B.
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      • Reply to: Correspondence on “Clinical features and evolution of bacterial infection-related acute-on-chronic liver failure”
        Journal of HepatologyVol. 75Issue 4
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          Firstly, the authors would like to thank Dr. Sundaram1 and Dr. Fischer et al.2 for their interest in our paper.3 We also want to thank Dr. Fischer for providing some local data on a subgroup of patients with cirrhosis who were admitted to the intensive care unit (ICU). Comparing their patients to the entire group of patients in the global study, Dr. Fischer’s patients were a lot sicker, by virtue of the fact that they required ICU care. Many of them had multiple complications of cirrhosis, multiple infection sites, many more nosocomial infections (which are usually associated with a worse outcome),4 had a higher qSOFA score or sepsis.
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