RESUMO
BACKGROUND & AIMS: We investigated the effect of albumin treatment (20% solution) on hypoalbuminemia, cardiocirculatory dysfunction, portal hypertension, and systemic inflammation in patients with decompensated cirrhosis with and without bacterial infections. METHODS: We performed a prospective study to assess the effects of long-term (12 weeks) treatment with low doses (1 g/kg body weight every 2 weeks) and high doses (1.5 g/kg every week) of albumin on serum albumin, plasma renin, cardiocirculatory function, portal pressure, and plasma levels of cytokines, collecting data from 18 patients without bacterial infections (the Pilot-PRECIOSA study). We also assessed the effect of short-term (1 week) treatment with antibiotics alone vs the combination of albumin plus antibiotics (1.5 g/kg on day 1 and 1 g/kg on day 3) on plasma levels of cytokines in biobanked samples from 78 patients with bacterial infections included in a randomized controlled trial (INFECIR-2 study). RESULTS: Circulatory dysfunction and systemic inflammation were extremely unstable in many patients included in the Pilot-PRECIOSA study; these patients had intense and reversible peaks in plasma levels of renin and interleukin 6. Long-term high-dose albumin, but not low-dose albumin, was associated with normalization of serum level of albumin, improved stability of the circulation and left ventricular function, and reduced plasma levels of cytokines (interleukin 6, granulocyte colony-stimulating factor, interleukin 1 receptor antagonist, and vascular endothelial growth factor) without significant changes in portal pressure. The immune-modulatory effects of albumin observed in the Pilot-PRECIOSA study were confirmed in the INFECIR-2 study. In this study, patients given albumin had significant reductions in plasma levels of cytokines. CONCLUSIONS: In an analysis of data from 2 trials (Pilot-PRECIOSA study and INFECIR-2 study), we found that albumin treatment reduced systemic inflammation and cardiocirculatory dysfunction in patients with decompensated cirrhosis. These effects might be responsible for the beneficial effects of albumin therapy on outcomes of patients with decompensated cirrhosis. ClinicalTrials.gov, Numbers: NCT00968695 and NCT03451292.
Assuntos
Albuminas/administração & dosagem , Infecções Bacterianas/imunologia , Citocinas/imunologia , Hipertensão Portal/fisiopatologia , Hipoalbuminemia/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Albumina Sérica/metabolismo , Infecções Bacterianas/complicações , Infecções Bacterianas/fisiopatologia , Estudos de Casos e Controles , Feminino , Hemodinâmica , Humanos , Hipertensão Portal/etiologia , Hipoalbuminemia/etiologia , Hipoalbuminemia/imunologia , Hipoalbuminemia/fisiopatologia , Inflamação , Circulação Hepática , Cirrose Hepática/complicações , Cirrose Hepática/imunologia , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pressão na Veia Porta , Sistema Porta , Estudos Prospectivos , Renina/sangueRESUMO
BACKGROUND & AIMS: We performed a randomized trial to determine whether albumin should be administered to patients with infections unrelated to spontaneous bacterial peritonitis (SBP). METHODS: We performed a multicenter, open-label trial in which 118 patients with cirrhosis, non-SBP infections, and additional risk factors for poor outcome were randomly assigned to receive antibiotics plus albumin (study group; n = 61) or antibiotics alone (control group; n = 57). The primary outcome was in-hospital mortality; secondary outcomes were effect of albumin on disease course. RESULTS: There were no significant differences at baseline between groups in results from standard laboratory tests, serum markers of inflammation, circulatory dysfunction, or liver severity scores. However, the combined prevalence of acute on chronic liver failure (ACLF) and kidney dysfunction was significantly higher in the study group (44.3% vs 24.6% in the control group; P = .02), indicating greater baseline overall severity. There was no significant difference in the primary outcome between groups (13.1% in the study group vs 10.5% in the control group; P = .66). Circulatory and renal functions improved in only the study group. A significantly higher proportion of patients in the study group had resolution of ACLF (82.3% vs 33.3% in the control group; P = .03). A significantly lower proportion of patients in the study group developed nosocomial infections (6.6% vs 24.6% in the control group; P = .007). CONCLUSIONS: In a randomized trial of patients with advanced cirrhosis and non-SBP infections, in-hospital mortality was similar between those who received albumin plus antibiotics vs those who received only antibiotics (controls). However, patients given albumin were sicker at baseline and, during the follow-up period, a higher proportion had ACLF resolution and a lower proportion had nosocomial infections. ClinicalTrials.gov no: NCT02034279.
Assuntos
Insuficiência Hepática Crônica Agudizada , Infecções Bacterianas , Peritonite , Albuminas , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Humanos , Cirrose Hepática/complicações , Peritonite/tratamento farmacológico , Peritonite/epidemiologiaRESUMO
BACKGROUND & AIMS: Clinical course and risk factors of death in non-spontaneous bacterial peritonitis (SBP) infections are poorly known. We assessed the prevalence of acute kidney injury (AKI) and type-1 hepatorenal syndrome (HRS), hospital, 30-day and 90-day mortality and risk factors of death in 441 decompensated patients. METHODS: Analysis of 615 non-SBP infections (161 urinary infections (UTI), 95 cellulitis, 92 suspected infections, 92 bacteraemias, 84 pneumonias, 21 bronchitis, 18 cholangitis, 15 spontaneous empyema, 13 secondary peritonitis, 24 other). RESULTS: Ninety-six percent of infections solved. AKI and type-1 HRS were developed in 37% and 9% of infections respectively. Overall hospital, 30-day and 90-day mortality rates were 11%, 12% and 18% respectively. Clinical course and mortality differed markedly across infections. Endocarditis, osteoarticular infections, pneumonia, spontaneous bacteraemia, cholangitis, secondary peritonitis and UTI showed higher rates of AKI. Prevalence of type-1 HRS was not significantly different among infections. Endocarditis, secondary peritonitis, pneumonia and bacteraemia showed lower rates of renal impairment resolution and higher hospital mortality associated with AKI (42% vs 12%, P<.0001) or type-1 HRS (71% vs 27%, P=.003) than the rest of infections. Age (HR: 1.04), serum sodium (HR: 0.91), serum bilirubin (HR: 1.06), INR (HR: 1.91), hepatic encephalopathy (HR: 2.44), ascites (HR: 3.06) and multidrug-resistant isolation (HR: 2.27) at infection diagnosis were independent predictors of death during hospitalization. CONCLUSIONS: Non-SBP infections constitute a heterogeneous group regarding clinical course and prognosis. Endocarditis, secondary peritonitis, pneumonia and bacteraemia show worse prognosis. The combination of data of liver and renal dysfunction and of the type of infection allows the identification of patients with poor prognosis.