Accepted Article
DR. CRISTINA LUCIDI (Orcid ID : 0000-0003-3173-9767)
Article type
: Original Articles
Handling Editor: Juan Abraldes
A LOW MUSCLE MASS INCREASES MORTALITY IN COMPENSATED CIRRHOTIC PATIENTS WITH SEPSIS Cristina Lucidi1, Barbara Lattanzi1, Vincenza Di Gregorio1, Simone Incicco 1, Daria D’Ambrosio1, Mario Venditti2, Oliviero Riggio1, Manuela Merli1. 1
Department of Clinical Medicine, Gastroenterology and Hepatology Unit, La Sapienza University of Rome
2
Department of Infectious Disease, La Sapienza University of Rome
Corresponding Author: Prof. Manuela Merli Department of Clinical Medicine, Gastroenterology Unit, La Sapienza University of Rome Tel/fax: +39-0649972002;
[email protected] Abbreviations: MELD: Model for End stage Liver Disease; HIV: Human Immunodeficiency Virus; MAMC: mid-arm muscle circumference; HRS: Hepatorenal syndrome; HE: Hepatic encephalopathy.
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/liv.13691 This article is protected by copyright. All rights reserved.
Accepted Article
Conflict of interest: The authors declare that no conflict of interest exists concerning this paper Financial support: None
Abstract Background & Aims Severe infections and muscle wasting are both associated to poor outcome in cirrhosis. A possible synergic effect of these two entities in cirrhotic patients has not been previously investigated. We aimed at analyzing if a low muscle mass may deteriorate the outcome of cirrhotic patients with sepsis. Methods Consecutive cirrhotic patients hospitalized for sepsis were enrolled. Patients were classified for the severity of liver impairment (Child-Pugh class) and for the presence of “low muscle mass” (mid-arm muscle circumference 20 breaths per minute, white blood cell count < 4000 cells/mm³ or > 12000 cells/mm³). The exclusion criteria were age < 18 or > 80 years, evidence of current malignancy (except for hepatocellular carcinoma within Milan criteria or non-melanocytic skin cancer) and independent condition of immunodeficiency (such as concomitant HIV infection or chronic immunosuppressive treatment). At admission, relevant baseline demographic, clinical and biochemical data were recorded. The severity of liver disease was assessed using the Child– Pugh and the model of end-stage liver disease (MELD) scores. Morbidity and in-hospital mortality were registered. The local Ethical Committee Review Board (comitato etico “Policlinico Umberto I”) approved the study, and all the participants signed a written informed consent.
Characterization of the infections and management A detailed form concerning each infectious episode was always prepared; this form included the epidemiological and microbiological characteristics, the antibiotic treatment and its effectiveness. The clinical course (i.e., efficacy of the currently recommended empirical antibiotic therapy, complications related to infection, final resolution, and hospital mortality) during hospitalization was always recorded. In case of a second episode of infection in the same patient this was also registered. The diagnosis of bacterial infection was based on criteria previously reported10. According to their epidemiological characteristics, infections were classified as follows: (1) Hospital acquired (HA) in case of infection onset at least 48 hours after the admission, or within 10 days of leaving the hospital, or if the patient was coming from another department. (2) Health-care associated (HCA) if the diagnosis was made at hospital admission or within 48 hours of hospitalization in patients with any of the following criteria: a) had attended a This article is protected by copyright. All rights reserved.
Accepted Article
hospital or a hemodialysis clinic or received intravenous chemotherapy in the last 30 days, b) was hospitalized for at least two days or had undergone surgery during the 90 days before infection or c) had resided in a nursing home or a long-term care facility. (3) Community acquired (CA) if the diagnosis of infection was made within 48 hours of hospitalization and the patient did not fulfill the criteria for HCA infection (had no recent contact with the healthcare system) 12. Infections were classified as "Multidrug-resistant" (MDR) when the pathogens were resistant to at least one component in three or more antimicrobial classes13. An empirical antibiotic treatment was always started within 24 hours from patient’s presentation at the emergency department and after an adequate culture sampling. Management of bacterial infection was based on international guidelines14 according to the different epidemiological classes (i.e. CA regimens were mainly based on third-generation cephalosporins, and HA and HCA regimens were based on carbapenems, alone or in combination with other antibiotics). In case of colture-positive infections the treatments was continued or discontinued according to the results of the antimicrobial susceptibility testing. The antibiotic treatment was ever set by a dedicated infectious disease specialist.
Nutritional assessment A detailed nutritional evaluation was performed in all patients and the following parameters were taken into consideration: (a) Body mass index (using the estimated dry body weight when needed). (b) Mid-Arm-Muscle-Circumference (MAMC) and Triceps Skinfold-Thickness (TSF) of the non-dominant arm measured using a Harpenden Skinfold Caliper (John Bull British Indicators Ltd, St. Albans, UK). A diagnosis of “low muscle mass” was made in patients having a MAMC
