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Variceal bleeding is a serious complication in cirrhotic patients and is related to increased expression of inflammatory mediators that accentuate circulatory dysfunction. The study aims to evaluate the performance of high mobility protein group 1 (HMG1) and interleukin-6 (IL-6) as predictors of acute kidney injury (AKI), infection and death in these patients. Fifty patients who were diagnosed with advanced chronic liver disease with variceal bleeding were included. The mean age was 52.8 ± 10.8 years, and 33 (66%) were male. Twenty-one (42%) patients were classified as Child-Pugh C, 21 (42%) Child-Pugh B and 8 (16%) Child-Pugh A. The mean HMG1 serum level was 2872.36 pg/mL ± 2491.94, and the median IL-6 serum level was 47.26 pg/mL (0-1102.4). In AKI, the serum level of HMG1 that performed best on the ROC curve was 3317.9 pg/mL. The IL-6 serum level was not associated with AKI. HMG1 and IL-6 cut-off values that better predicted infection were 3317.9 pg/mL and 72.9 pg/mL, and for mortality, the values were 2668 pg/mL and 84.5 pg/mL, respectively. In multivariate analysis, the variables that were associated with AKI and infection outcomes were model for end-stage liver disease and HMG1. Infections were related to the risk of death. Clinical and laboratory variables related to the outcomes were identified. Serum levels of HMG1 were associated with AKI and infection and had good performance in the ROC curve. IL-6 levels were not maintained in logistic regression outcomes but had good performance in infection and death outcomes. Such data will be useful for comparisons and possible future validations.

Introdução: O sangramento resultante da ruptura de varizes esofagogástricas é considerado complicação grave resultante da hipertensão portal e potencialmente fatal nos pacientes com doença hepática crônica avançada descompensada. Nestes pacientes, a expressão aumentada de citocinas acentua a disfunção circulatória por meio da inflamação sistêmica. Entre os mediadores inflamatórios deste processo, destacam-se o grupo de proteínas 1 de alta mobilidade (HMG1) e a interleucina-6 (IL6). Entretanto, o papel desses biomarcadores como preditores de morbimortalidade nestes pacientes ainda não é conhecido. Objetivos: Avaliar o desempenho da HMG1 e Interleucina 6 como preditores de desfechos resultantes do sangramento por varizes esofagogástricas em pacientes com doença hepática crônica avançada descompensada. Métodos: foram incluídos 50 pacientes de ambos os sexos, com idade superior a 18 anos, internados no Hospital das Clínicas da Universidade Federal de Minas Gerais, que apresentaram diagnóstico de doença hepática crônica avançada descompensada e hemorragia digestiva resultante da ruptura de varizes gastroesofágicas. Dados demográficos, clínicos e laboratoriais foram coletados para investigar os preditores de injúria renal aguda, infecção e mortalidade. Resultados: a média de idade foi de 52,8±10,8 anos, sendo 33 (66%) do sexo masculino. Dentre as causas de doença hepática crônica avançada descompensada, o etilismo foi o mais comum,18 (36%) casos, seguido pela hepatite crônica pelo vírus C, 11 pacientes (22%). Vinte e um (42%) pacientes foram classificados como Child-Pugh C, 21 (42%) Child-Pugh B e 8 (16%) Child-Pugh A. A média do MELD foi de 16,46 ±5,98 e MELDNa de 18,02 ±7,35. A média do nível sérico do HMG1 foi de 2872,36pg/mL ± 2491,94 e a mediana do nível sérico de IL-6 foi de 47,26pg/mL (0-1102,4). A IRA esteve presente em 14 (28%) pacientes, as complicações infecciosas foram diagnosticadas em 13 (26%) pacientes e 7 (14%) pacientes evoluíram para o óbito. Na análise multivariada, as variáveis que estiveram associadas aos desfechos IRA e infecção foram MELD e HMG1. Na injúria renal aguda, o nível sérico de HMG1 que apresentou melhor desempenho na curva ROC foi 3317,9 pg/mL. A área sob a curva foi de 0,799 e as taxas de sensibilidade e especificidade foram de 76,9% e 72,2%. A infecção relacionou-se ao risco de óbito. Os valores séricos dos pontos de corte que predizeram melhor infecção foram 3317,9pg/mL e 72,9pg/mL para HMG1 e IL-6, respectivamente. A área sob a curva foi de 0,848 para a HMG1 e de 0,859 para a IL6 e as taxas de sensibilidade e especificidade foram de 92,3% e 77,8% para nível sérico de HMG1 e de 90,9% e 78,4% para nível sérico de IL-6. Para o desfecho mortalidade, os pontos de corte com melhor acurácia foram 2668pg/mL e 84,5pg/mL para a HMG1 e IL-6, respectivamente. A área sob a curva foi de 0,794 para a HMG1 e de 0,848 para a IL-6 e as taxas de sensibilidade e especificidade foram de 85,7% e 57,1%, para nível sérico de HMG1 e de 85,7% e 80,5% para nível sérico de IL-6. Conclusão: por meio deste estudo, foi possível identificar variáveis clínicas e laboratoriais relacionadas aos desfechos injúria renal aguda, infecção e mortalidade na fase aguda do sangramento resultante da ruptura de varizes esofagogástricas em pacientes com doença. Os níveis séricos de HMG1 foram mais elevados nos pacientes que desenvolveram injúria renal aguda, infecção e evoluíram para o óbito quando comparados com pacientes que não apresentaram estes desfechos. Em relação aos níveis séricos de IL-6, não houve diferença entre os grupos de pacientes que apresentaram ou não injúria renal aguda e os valores foram mais elevados para os desfechos infecção e óbito. Tais dados servirão para comparações e possíveis validações futuras. Introduction: Bleeding resulting from rupture of esophagogastric varices is considered a serious complication resulting from portal hypertension and potentially fatal in patients with advanced chronic liver disease. In these patients, increased cytokine expression accentuates circulatory dysfunction through systemic inflammation. Among the inflammatory mediators of this process are the high mobility proteins 1 (HMG1) and interleukin-6 (IL-6). However, the role of these biomarkers as predictors of morbidity and mortality in these patients is not yet known. Objectives: To evaluate the performance of HMG1 and Interleukin 6 as predictors of outcomes resulting from esophagogastric variceal bleeding in patients with advanced decompensated chronic liver disease. Methods: Fifty patients of both sexes, aged over 18 years, hospitalized at the Clinical Hospital of the Federal University of Minas Gerais, Brazil, who had been diagnosed with decompensated advanced chronic liver disease and gastrointestinal bleeding due to the rupture of gastroesophageal varices, were included. Clinical and laboratory data were collected to investigate the predictors of acute renal injury, infection, and mortality. Results: mean age was 52.8 ± 10.8 years, of which 33 (66%) were male. Among the causes of chronic liver disease, alcoholism was the most common, 18 (36%) cases, followed by chronic hepatitis C virus, 11 patients (22%). Twenty-one (42%) patients were classified as Child-Pugh C, 21 (42%) Child-Pugh B and 8 (16%) Child-Pugh A. The mean MELD was 16.46 ± 5.98 and MELD-Na of 18.02 ± 7.35. The mean serum HMG1 level was 2872.36pg / mL ± 2491.94 and the median serum IL-6 level was 47.26pg / mL (0-1102.4). The acute renal injury was present in 14 (28%) patients; the infectious complications were diagnosed in 13 (26%) patients and 7 (14%) patients evolved to death. In the multivariate analysis, the variables that were associated with the acute renal injury and infection outcomes were MELD and HMG1. In acute renal injury, the serum HMG1 level that presented the best ROC curve yield was 3317.9 pg / mL. The area under the curve was 0.799 and the sensitivity and specificity rates were 76.9% and 72.2%. The infection was related to the risk of death. Serum values of the cutoff points that predicted the best infection were 3317.9pg / mL and 72.9pg / mL for HMG1 and IL-6, respectively. The area under the curve was 0.848 for HMG1 and 0.859 for IL-6 and the sensitivity and specificity rates were 92.3% and 77.8% for serum HMG1 and 90.9% and 78,4% for serum IL-6 level. For endpoint mortality, the cutoff points with best accuracy were 2668pg / mL and 84.5pg / mL for HMG1 and IL-6, respectively. The area under the curve was 0.794 for HMG1 and 0.848 for IL-6, and the sensitivity and specificity rates were 85.7% and 57.1% for serum HMG1 and 85.7% and 80.5% for serum IL-6 level. Conclusion: Through this study, it was possible to identify clinical and laboratory variables related to the outcomes acute kidney injury, infection and mortality in the acute phase of bleeding resulting from rupture of esophagogastric varices in patients with disease. Serum HMG1 levels were higher in patients who developed acute kidney injury, infection, and died as compared to patients who did not have these outcomes. Regarding serum IL-6 levels, there was no difference between the groups of patients with or without acute kidney injury and the values were higher for the infection and death outcomes. Such data will serve for comparisons and possible future validations.

BACKGROUND: Gastroesophageal varices and associated bleeding are a major cause of morbidity and mortality in cirrhotic patients. OBJECTIVE: To evaluate the potential role of the biomarkers HMGB1 (High Mobility Group Box 1) and IL-6 (Interleukin-6) as predictors of infection, acute kidney injury and mortality in these patients. METHODS: It is a prospective, observational study that included 32 cirrhotic patients with variceal bleeding. RESULTS: The subjects’mean age was 52±5 years and 20 (62.5%) were male. The average MELD was 17.53±5 and the average MELD-Na was 20.63±6.06. Thirty patients (93.3%) patients were Child-Pugh class B or C. Infection was present in 9 subjects (28.1%), acute kidney injury was present in 6 (18.1%) and 4 (12.5%) patients died. The median serum levels of HMGB1 were 1487 pg/mL (0.1 to 8593.1) and the median serum level of IL-6 was 62.1 pg/mL (0.1 to 1102.4). The serum levels of HMGB1 and IL-6 were significantly higher in patients who developed infection, acute kidney injury and death (P