Infection in liver transplantation: current epidemiology and predictive factors

Orientador: Elza Cotrim SoaresDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: A infecção é uma das complicações mais freqüentes e graves após o transplante hepático. A evolução de técnicas operatórias e mudanças nos protocolos de transplante podem ter mudado a epidemiologia e os fatores de risco para infecções após o transplante hepático. Objetivos: estudar a epidemiologia das infecções, identificar fatores de risco para infecções e verificar a influência das infecções na mortalidade após o transplante de fígado. Pacientes e métodos: estudo prospectivo de transplantados de fígado no Hospital Clínico e Provincial de Barcelona (Espanha) entre julho de 2000 e agosto de 2001. Foram coletados dados de incidência, etiologia, tipos de infecção e fatores de risco para infecção, assim como causas de mortalidade. Os fatores de risco foram identificados em análise multivariada de regressão de Cox. Resultados: Dos 81 transplantados no período de estudo, 52 (64%) tiveram infecção, sendo que 49 (60%) apresentaram 89 episódios de infecção bacteriana, metade destes nos primeiros 13 dias após o transplante. Infecções intra-abdominais (23) e urinárias (22) foram as mais comumente diagnosticadas. Bacilos Gram-negativos foram identificados em 65% das infecções com cultura positiva. Bactérias resistentes a múltiplos antibióticos estiveram presentes em 18,4% destas infecções. O citomegalovírus foi responsável por 16 (20%) episódios de infecção, que foram sintomáticos em 12. Nove (11%) pacientes tiveram infecção por fungos. Os fatores de risco independentes para infecção bacteriana foram insuficiência renal antes do transplante (RR: 2,54; p=0,004), presença de hemoperitônio (RR: 2,85; p=0,001) e anastomose biliar tipo colédoco-jejunal (RR: 2,89; p=0,015). Para infecções oportunistas virais e fúngicas, os fatores de risco encontrados foram: desenvolvimento de insuficiência renal logo após o transplante (RR: 6,29; p<0,001), necessidade de hemodiálise (RR: 9,55; p=0,016) e uso de anastomose biliar tipo colédoco-jejunal (RR: 7,34; p<0,001). Onze pacientes morreram durante o seguimento (13%), sendo 8 por causa infecciosa. Infecções oportunistas (RR: 4,5; p=0,026) e necessidade de hemodiálise (RR=99,7; p<0,001) foram os fatores de risco independentes de mortalidade. Conclusões: As infecções são, ainda, complicações freqüentes e graves no período após o transplante de fígado, e estão relacionadas a fatores cirúrgicos e insuficiência renal antes e depois do transplanteAbstract: Infection is a frequent and severe complication of liver transplantation. Recent surgical and medical advances may have influenced epidemiology and risk factors of this complication. Aims: To study the epidemiology of infection in a prospective series of liver transplant recipients and to identify predictive factors for infection and its effects on survival. Patients and methods: patients consecutively submitted to liver transplantation between July 2000 and August 2001at the Clinical Hospital of Barcelona (Spain) were prospectively followed. The study analyzed data on incidence, etiology, risk factors and mortality. Results: Eighty-one patients were prospectively followed for 16_6 months. Forty-nine patients (60%) developed bacterial infections, half of them within 2 weeks after transplantation. Intraabdominal (23) and urinary infections (22) were the most frequent demonstrated infections. Gram-negative bacilli were isolated in 65% of culture-positive infections. Multiresistant bacteria, mainly Pseudomonas aeruginosas, accounted for 18,4% of these infections. Opportunistic viral and fungal infections were diagnosed in 21 patients (26%). There were 16 cytomegalovirus infection or disease (20%) and 9 fungal infections (11%). Independent risk factors for bacterial infection were renal impairment before transplantation (RR: 2,54; p=0,004), hemoperitoneum (RR: 2,85; p=0,001), and hepaticojejunostomy (RR: 2,89; p=0,015). Early posttransplant renal impairment with (RR: 9,55; p=0,016) or without hemodialysis requirement (RR: 6,29; p<0,001) and hepaticojejunostomy (RR: 7,34; p<0,001) were predictive factors for opportunistic infections. Eleven patients died during follow-up (13%), mainly because of sepsis (8 patients). Opportunistic infections (RR: 4.5; p=0.026) and hemodialysis requirement (RR=99.7; p<0.001) were the only identified independent predictors of mortality. Conclusions: Infections are still a frequent and severe complication following liver transplantation and are related to surgical factors and poor peritransplant renal functionMestradoClinica MedicaMestre em Clinica Medic

Prevalence and risk factors of infections by multiresistant bacteria in cirrhosis: A prospective study

Epidemiology, risk factors, and clinical effect of infections by multiresistant bacteria in cirrhosis are poorly known. This work was a prospective evaluation in two series of cirrhotic patients admitted with infection or developing infection during hospitalization. The first series was studied between 2005 and 2007 (507 bacterial infections in 223 patients) and the second between 2010 and 2011 (162 bacterial infections in 110 patients). In the first series, 32% of infections were community acquired (CA), 32% healthcare associated (HCA), and 36% nosocomial. Multiresistant bacteria (92 infections; 18%) were isolated in 4%, 14%, and 35% of these infections, respectively (P < 0.001). Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E; n = 43) was the main multiresistant organism identified, followed by Pseudomonas aeruginosa (n = 17), methicillin-resistant Staphylococcus aureus (n = 14), and Enterococcus faecium (n = 14). The efficacy of currently recommended empirical antibiotic therapy was very low in nosocomial infections (40%), compared to HCA and CA episodes (73% and 83%, respectively; P < 0.0001), particularly in spontaneous bacterial peritonitis, urinary tract infection, and pneumonia (26%, 29%, and 44%, respectively). Septic shock (26% versus 10%; P < 0.0001) and mortality rate (25% versus 12%; P = 0.001) were significantly higher in infections caused by multiresistant strains. Nosocomial origin of infection (hazard ratio [HR], 4.43), long-term norfloxacin prophylaxis (HR, 2.69), recent infection by multiresistant bacteria (HR, 2.45), and recent use of β-lactams (HR, 2.39) were independently associated with the development of multiresistant infections. Results in the second series were similar to those observed in the first series. Conclusions: Multiresistant bacteria, especially ESBL-producing Enterobacteriaceae, are frequently isolated in nosocomial and, to a lesser extent, HCA infections in cirrhosis, rendering third-generation cephalosporins clinically ineffective. New antibiotic strategies tailored according to the local epidemiological patterns are needed for the empirical treatment of nosocomial infections in cirrhosis. © 2011 American Association for the Study of Liver Diseases

Brazilian society of hepatology recommendations for the diagnosis and management of autoimmune diseases of the liver

ABSTRACT In order to draw evidence-based recommendations concerning the management of autoimmune diseases of the liver, the Brazilian Society of Hepatology has sponsored a single-topic meeting in October 18th, 2014 at São Paulo. An organizing committee comprised of seven investigators was previously elected by the Governing Board to organize the scientific agenda as well as to select twenty panelists to make a systematic review of the literature and to present topics related to the diagnosis and treatment of autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis and their overlap syndromes. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of those recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present paper is the final version of the reviewed manuscript organized in topics, followed by the recommendations of the Brazilian Society of Hepatology

Brazilian society of hepatology recommendations for the diagnosis and management of autoimmune diseases of the liver

ABSTRACT In order to draw evidence-based recommendations concerning the management of autoimmune diseases of the liver, the Brazilian Society of Hepatology has sponsored a single-topic meeting in October 18th, 2014 at São Paulo. An organizing committee comprised of seven investigators was previously elected by the Governing Board to organize the scientific agenda as well as to select twenty panelists to make a systematic review of the literature and to present topics related to the diagnosis and treatment of autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis and their overlap syndromes. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of those recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present paper is the final version of the reviewed manuscript organized in topics, followed by the recommendations of the Brazilian Society of Hepatology

Epidemiology and effects of bacterial infections in patients with cirrhosis worldwide

Bacterial infections are common and life-threatening in patients with cirrhosis. Little is known about the epidemiology of bacterial infections in different regions. We performed a multicenter prospective intercontinental study to assess the prevalence and outcomes of bacterial and fungal infections in patients with cirrhosis. METHODS: We collected data from 1302 hospitalized patients with cirrhosis and bacterial or fungal infections at 46 centers (15 in Asia, 15 in Europe, 11 in South America, and 5 in North America) from October 2015 through September 2016. We obtained demographic, clinical, microbiology, and treatment data at time of diagnosis of infection and during hospitalization. Patients were followed until death, liver transplantation, or discharge. RESULTS: The global prevalence of multidrug-resistant (MDR) bacteria was 34% (95% confidence interval 31%-37%). The prevalence of MDR bacteria differed significantly among geographic areas, with the greatest prevalence in Asia. Independent risk factors for infection with MDR bacteria were infection in Asia (particularly in India), use of antibiotics in the 3 months before hospitalization, prior health care exposure, and site of infection. Infections caused by MDR bacteria were associated with a lower rate of resolution of infection, a higher incidence of shock and new organ failures, and higher in-hospital mortality than those caused by non-MDR bacteria. Administration of adequate empirical antibiotic treatment was independently associated with improved in-hospital and 28-day survival. CONCLUSIONS: In a worldwide study of hospitalized patients, we found a high prevalence of infection with MDR bacteria in patients with cirrhosis. Differences in the prevalence of MDR bacterial infections in different global regions indicate the need for different empirical antibiotic strategies in different continents and countries. While we await new antibiotics, effort should be made to decrease the spread of MDR bacteria in patients with cirrhosis156513681380This study was supported by a grant from the Italian Ministry of Education,University and Research (DOR1678487/16). PG is recipient of an ICREA Academia awar

Energy calibration and resolution of the CMS electromagnetic calorimeter in pp collisions at s\sqrt{s} = 7 TeV

The energy calibration and resolution of the electromagnetic calorimeter (ECAL) of the CMS detector have been determined using proton-proton collision data from LHC operation in 2010 and 2011 at a centre-of-mass energy of sqrt(s)=7 TeV with integrated luminosities of about 5 inverse femtobarns. Crucial aspects of detector operation, such as the environmental stability, alignment, and synchronization, are presented. The in-situ calibration procedures are discussed in detail and include the maintenance of the calibration in the challenging radiation environment inside the CMS detector. The energy resolution for electrons from Z-boson decays is better than 2% in the central region of the ECAL barrel (for pseudorapidity abs(eta)<0.8) and is 2-5% elsewhere. The derived energy resolution for photons from 125 GeV Higgs boson decays varies across the barrel from 1.1% to 2.6% and from 2.2% to 5% in the entraps. The calibration of the absolute energy is determined from Z to e+e- decays to a precision of 0.4% in the barrel and 0.8% in the endcaps

The Nd Break-Up Process in Leading Order in a Three-Dimensional Approach

A measurement of total and fiducial inclusive W and Z boson production cross sections in pp collisions at sqrt(s)=8 TeV is presented. Electron and muon final states are analyzed in a data sample collected with the CMS detector corresponding to an integrated luminosity of 18.2 +/- 0.5 inverse picobarns. The measured total inclusive cross sections times branching fractions are sigma(pp to W X) B(W to l nu ) = 12.21 +/- 0.03 (stat.) +/- 0.24 (syst.) +/- 0.32 (lum.) nb and sigma(pp to Z X) B(Z to l+ l-) = 1.15 +/- 0.01 (stat.) +/- 0.02 (syst.) +/- 0.03 (lum.) nb for the dilepton mass in the range of 60 to 120 GeV. The measured values agree with next-to-next-to-leading-order QCD cross section calculations. Ratios of cross sections are reported with a precision of 2%. This is the first measurement of inclusive W and Z boson production in proton-proton collisions at sqrt(s)=8 TeV

Measurement of the W+W- cross section in pp collisions at sqrt(s) = 7 TeV and limits on anomalous WW gamma and WWZ couplings

A measurement of W+W- production in pp collisions at sqrt(s) = 7 TeV is presented. The data were collected with the CMS detector at the LHC, and correspond to an integrated luminosity of 4.92 +/- 0.11 inverse femtobarns. The W+W- candidates consist of two oppositely charged leptons, electrons or muons, accompanied by large missing transverse energy. The W+W- production cross section is measured to be 52.4 +/- 2.0 (stat.) +/- 4.5 (syst.) +/- 1.2 (lum.) pb. This measurement is consistent with the standard model prediction of 47.0 +/- 2.0 pb at next-to-leading order. Stringent limits on the WW gamma and WWZ anomalous triple gauge-boson couplings are set