Aim: The aim of the study was to assess the influence of non-antibiotic medicationcontributing to MDRO colonisation.Methods: Three hundred twenty-four patients with AD and ACLF admitted to the... Show moreAim: The aim of the study was to assess the influence of non-antibiotic medicationcontributing to MDRO colonisation.Methods: Three hundred twenty-four patients with AD and ACLF admitted to the ICUof Frankfurt University Hospital with MDRO screening were included. Regressionmodels were performed to identify drugs associated with MDRO colonisation.Another cohort (n = 129) from Barcelona was included to validate. A third multi-centre cohort (n = 203) with metagenomic sequencing data of stool was included todetect antibiotic resistance genes.Results: A total of 97 patients (30%) were identified to have MDRO colonisation and35 of them (11%) developed MDRO infection. Patients with MDRO colonisation hadsignificantly higher risk of MDRO infection than those without (p = 0.0098). Apartfrom antibiotic therapy (odds ratio (OR) 2.91, 95%-confidence interval (CI) 1.82–4.93,p < 0.0001), terlipressin therapy in the previous 14 days was the only independentcovariate associated with MDRO colonisation in both cohorts, the overall (OR 9.47,95%-CI 2.96–30.23, p < 0.0001) and after propensity score matching (OR 5.30, 95%-CI 1.22–23.03, p = 0.011). In the second cohort, prior terlipressin therapy was a riskfactor for MDRO colonisation (OR 2.49, 95% CI 0.911–6.823, p = 0.075) and associ-ated with risk of MDRO infection during follow-up (p = 0.017). The validation cohortdemonstrated that antibiotic inactivation genes were significantly associated withterlipressin administration (p = 0.001).Conclusions: Our study reports an increased risk of MDRO colonisation in patientswith AD or ACLF, who recently received terlipressin therapy, while other commonlyprescribed non-antibiotic co-medications had negligible influence. Future prospec-tive trials are needed to confirm these results. Show less
Background & Aims: Acute decompensation (AD) of cirrhosis may present without acute-on-chronic liver failure (ACLF) (ADNo ACLF), or with ACLF (AD-ACLF), defined by organ failure(s). Herein, we... Show moreBackground & Aims: Acute decompensation (AD) of cirrhosis may present without acute-on-chronic liver failure (ACLF) (ADNo ACLF), or with ACLF (AD-ACLF), defined by organ failure(s). Herein, we aimed to analyze and characterize the precipitants leading to both of these AD phenotypes. Methods: The multicenter, prospective, observational PREDICT study (NCT03056612) included 1,273 non-electively hospitalized patients with AD (No ACLF = 1,071; ACLF = 202). Medical history, clinical data and laboratory data were collected at enrolment and during 90-day follow-up, with particular attention given to the following characteristics of precipitants: induction of organ dysfunction or failure, systemic inflammation, chronology, intensity, and relationship to outcome. Results: Among various clinical events, 4 distinct events were precipitants consistently related to AD: proven bacterial infections, severe alcoholic hepatitis, gastrointestinal bleeding with shock and toxic encephalopathy. Among patients with precipitants in the AD-No ACLF cohort and the AD-ACLF cohort (38% and 71%, respectively), almost all (96% and 97%, respectively) showed proven bacterial infection and severe alcoholic hepatitis, either alone or in combination with other events. Survival was similar in patients with proven bacterial infections or severe alcoholic hepatitis in both AD phenotypes. The number of precipitants was associated with significantly increased 90day mortality and was paralleled by increasing levels of surrogates for systemic inflammation. Importantly, adequate first-line antibiotic treatment of proven bacterial infections was associated with a lower ACLF development rate and lower 90-day mortality. Conclusions: This study identified precipitants that are significantly associated with a distinct clinical course and prognosis in patients with AD. Specific preventive and therapeutic strategies targeting these events may improve outcomes in patients with decompensated cirrhosis. Lay summary: Acute decompensation (AD) of cirrhosis is characterized by a rapid deterioration in patient health. Herein, we aimed to analyze the precipitating events that cause AD in patients with cirrhosis. Proven bacterial infections and severe alcoholic hepatitis, either alone or in combination, accounted for almost all (96-97%) cases of AD and acute-on-chronic liver failure. Whilst the type of precipitant was not associated with mortality, the number of precipitant(s) was. This study identified precipitants that are significantly associated with a distinct clinical course and prognosis of patients with AD. Specific preventive and therapeutic strategies targeting these events may improve patient outcomes. (c) 2020 European Association for the Study of the Liver. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Show less
