Bacterial infection is a frequent trigger of acute-on-chronic liver failure (ACLF), syndrome that could also increase the risk of infection. This investigation evaluated prevalence and characteristics of bacterial and fungal infections causing and complicating ACLF, predictors of follow-up bacterial infections and impact of bacterial infections on survival.
Patients 407 patients with ACLF and 235 patients with acute decompensation (AD).
Results 152 patients (37%) presented bacterial infections at ACLF diagnosis; 46%(n=117) of the remaining 255 patients with ACLF developed bacterial infections during follow-up (4 weeks). The corresponding figures in patients with AD were 25% and 18% (p<0.001). Severe infections (spontaneous bacterial peritonitis, pneumonia, severe sepsis/shock, nosocomial infections and infections caused by multiresistant organisms) were more prevalent in patients with ACLF. Patients with ACLF and bacterial infections (either at diagnosis or during follow-up) showed higher grade of systemic inflammation at diagnosis of the syndrome, worse clinical course (ACLF 2-3 at final assessment: 47% vs 26%; p<0.001) and lower 90-day probability of survival (49% vs 72.5%;p<0.001) than patients with ACLF without infection. Bacterial infections were independently associated with mortality in patients with ACLF-1 and ACLF-2. Fungal infections developed in 9 patients with ACLF (2%) and in none with AD, occurred mainly after ACLF diagnosis (78%) and had high 90-day mortality (71%).
Conclusion Bacterial infections are extremely frequent in ACLF. They are severe and associated with intense systemic inflammation, poor clinical course and high mortality. Patients with ACLF are highly predisposed to develop bacterial infections within a short follow-up period and could benefit from prophylactic strategies.
- clinical course
- immune paralysis
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Contributors JF, JA, AA, CD, MP and VA participated in data analysis and interpretation. JF, JA, RW, TG, JM, ER, RJ, FS, TW, MH, PG and VA participated in the writing group. VA was responsible for obtaining funding and overall project collaboration.
Funding The CLIF Consortium is supported by an unrestricted grant form Grifols. Rajiv Jalan is supported by a comprehensive biomedical research center, UK grant.
Disclaimer The EASL-CLIF ConsortiumIt is a network of 63 European university hospitals, aimed at stimulating research on pathophysiology, diagnostic and treatment on Chronic Liver Failure. During the period 2009-2012 the EASL-CLIF Consortium had received unrestricted grants form Grifols and Gambro. Grifols has prolonged its unrestricted grant for an additional period of four years. There is no other support for the Consortium. Vicente Arroyo (Chairman), Mauro Bernardi (Vice Chairman) and members of the Steering Committee have no relationship with Grifols or Gambro other than conferences at international meetings (from which they may receive honorarium) or as investigators on specific projects unrelated to the Consortium. Up to now, the EASL-CLIF Consortium has not performed any study promoted by pharmaceutical companies. The scientific agenda of the EASL-CLIF Consortium and the specific research protocols are made exclusively by the Steering Committee members without any participation of pharmaceutical companies.
Competing interests Rajiv Jalan received research funding from Vital Therapies, has served on Scientific Advisory Board for Conatus Pharma and received lecture fees from Gambro andhas ongoing research collaboration with Gambro, Grifols and is the principal investigator of an Industry sponsored study (Sequana Medical). He is also inventor of a drug, L-ornithine phenyl acetate, which UCL has licensed to Ocera Therapeutics. Pere Ginès has received speaker honorarium and research funding from Grifols, served on the scientific advisory board for Ferring and Sequena and received research funding from Sequena. Vicente Arroyo and Javier Fernandez have received grant and research support from Grifols. All other authors declare that they have no conflict of interest.
Patient consent Obtained.
Ethics approval Local EECC.
Provenance and peer review Not commissioned; externally peer reviewed.
Correction notice This article has been corrected since it published Online First. The third author’s name has been corrected to Reiner Wiest.