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Abstract Details
Bacterial infections adversely influence the risk of decompensation and survival in compensated cirrhosis
J Hepatol. 2021 Apr 24;S0168-8278(21)00257-9. doi: 10.1016/j.jhep.2021.04.022.Online ahead of print.
Càndid Villanueva1, Agustín Albillos2, Joan Genescà3, Joan C Garcia-Pagan4, Anna Brujats5, José L Calleja6, Carles Aracil7, Rafael Bañares8, Rosa M Morillas9, María Poca10, Beatriz Peñas2, Salvador Augustin3, Juan G Abraldes11, Edilmar Alvarado10, Ferran Torres12, Jaume Bosch13, PreDesCI Study Investigators
Author information
1Hospital de la Santa Creu i Sant Pau. Biomedical Research Institute Sant Pau (IIB Sant Pau), Universitat Autònoma de Barcelona. 08025 Barcelona; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd). Electronic address: cvillanueva@santpau.cat.
2Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd); Hospital Universitario Ramón y Cajal. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS). Universidad de Alcalá. Madrid.
3Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd); Liver Unit. Department of Internal Medicine. Vall d'Hebron Hospital Universitari. Vall d'Hebron Institute of Research (VHIR). Vall d'Hebron Barcelona. Hospital Campus Universitat Autònoma de Barcelona.
4Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd); Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). University of Barcelona. Barcelona, Spain; Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver).
5Hospital de la Santa Creu i Sant Pau. Biomedical Research Institute Sant Pau (IIB Sant Pau), Universitat Autònoma de Barcelona. 08025 Barcelona.
6Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd); Hospital Universitario Puerta de Hierro. IDIPHIM, Universidad Autónoma de Madird. Madrid.
7Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomèdica (IRBLleida), Lleida.
8Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd); Hospital General Universitario Gregorio Marañón. IISGM. Universidad Complutense. Madrid.
9Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd); Liver Section. Hospital Universitari Germans Trias i Pujol, IGTP, Universitat Autònoma de Barcelona. Badalona.
10Hospital de la Santa Creu i Sant Pau. Biomedical Research Institute Sant Pau (IIB Sant Pau), Universitat Autònoma de Barcelona. 08025 Barcelona; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd).
11Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd); Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). University of Barcelona. Barcelona, Spain; Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver); Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Canada.
12Medical Statistics Core Facility, IDIBAPS, Hospital Clinic, Barcelona; Biostatistics Unit, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona.
13Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd); Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). University of Barcelona. Barcelona, Spain; Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver); University Clinic for Visceral Surgery and Medicine, Inselspital, Bern University, Switzerland.
Abstract
Background & aims: Prognosis of compensated cirrhosis is good until decompensation. In decompensated cirrhosis, bacterial infections (BIs) are common and increase the risk of death. The incidence and prognostic implications of BIs in compensated cirrhosis are less characterized. This study aimed to assess whether BIs influence the risk of decompensation and survival in patients with compensated cirrhosis.
Methods: This is a cohort study nested to the PREDESCI, a double-blind, multicenter RCT evaluating if β-blockers could prevent decompensation of cirrhosis. Patients with compensated cirrhosis and HVPG ≥10 mmHg were included. Development of BIs during follow-up was prospectively registered. Using a competing-risk time-dependent regression analysis, we investigated whether BIs affect the risk of decompensation and survival. Decompensation was defined as development of ascites, bleeding or overt encephalopathy.
Results: 201 patients were randomized and followed for a median of 36 months (IQR: 24-47 months). 34 patients (17%) developed BIs, which in 33 cases occurred before decompensation, and 29 (14%) developed ascites. Respiratory and urinary tract infections were the most frequent BIs. Cirrhosis decompensation occurred in 26% patients with BIs vs 16% without BIs. Patients with BIs had higher risk of decompensation (HR=2.93, 95%CI=1.02-8.42; P= 0.047) and of developing ascites (HR=3.55, 95%CI=1.21-10.47; P=0.022) than those without BIs. Risk of death was also higher in patients with BIs (SHR=6.93, 95%CI=2.64-18.18; P< 0.001), although in 71% of such cases decompensation occurred before death.
Conclusions: BIs have a marked impact on natural history of compensated cirrhosis, significantly increasing the risk of decompensation, mainly that of ascites, and increasing the risk of death, which usually occurs after decompensation. Our results suggest that BIs may constitute a target to prevent decompensation.
Lay summary: In decompensated cirrhosis bacterial infections are common and increase the mortality risk. However, the relevance of bacterial infections in compensated cirrhosis has not been well studied so far. This study shows that in patients with compensated cirrhosis and clinically significant portal hypertension, bacterial infections occur as frequently as the development of ascites, which is the most frequent decompensating event. Most of these infections are from the respiratory or urinary tract. Their development increases the risk of progression to decompensation, mainly by a higher risk of ascites, and also increases the risk of death which in most cases occurs after decompensation. Bacterial infections have a deep impact on the natural history of compensated cirrhosis and may represent a target to prevent decompensation. CLINICALTRIALS.