Caracterização imunocelular em coorte de pacientes cirróticos com resposta virológica sustentada obtida com drogas de ação direta para Hepatite C crônica
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Data
2020-11-11
Autores
Braz, Aline Márcia Marques [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
Pacientes cirróticos com hepatite C crônica, mesmo após resposta virológica sustentada (RVS), devem ser monitorados para avaliação da função hepática e rastreamento do carcinoma hepatocelular (CHC) a cada seis meses por toda a vida. Após o tratamento e depuração viral, inicia-se a fase de resolução da inflamação e regressão da fibrose. No entanto, avaliações por elastografia demonstram que 30 a 40% dos pacientes não apresentam diminuição da rigidez hepática após RVS. Este foi um estudo de coorte em pacientes cirróticos para identificar fatores imunológicos envolvidos na regressão da rigidez hepática na hepatite C crônica e caracterizar possíveis biomarcadores séricos de valor prognóstico. O universo amostral foi composto por 31 pacientes cirróticos que realizaram imunofenotipagem leucocitária, quantificação de citocinas/quimiocinas e inibidores de metaloproteinase (TIMP 1, 2, 3) no pré-tratamento (M1) e na avaliação da RVS (M2) (análise retrospectiva). Os critérios de inclusão foram: infecção pelo genótipo 1 do VHC, diagnóstico de cirrose, ausência de comorbidades de origem infecciosa, inflamatória ou neoplásica, não uso de imunossupressor e confirmação de RVS em M2. Os critérios de exclusão foram: transplante de fígado e/ou desenvolvimento de nódulos ou CHC durante o período de seguimento, ausência de exame de elastografia em M1 ou M3 (24 meses após RVS), resultado de elastografia hepática incompatível com cirrose e perda de seguimento. Os 16 pacientes incluídos foram novamente avaliados por imunofenotipagem, análises multiplex e elastografia 24 meses após RVS (M3) e classificados em regressores (R) e não-regressores (NR) (diminuição ≥25% de rigidez) (análise prospectiva). Os resultados da curva ROC, aprendizado de máquina (ML) e análise discriminante linear mostraram que a quantificação absoluta dos linfócitos TCD4 + foi o biomarcador mais importante para a predição da regressão (AUC = 0,90). Os pacientes NR apresentaram níveis de rigidez inferiores a R desde a quantificação basal (M1), enquanto as células NK aumentaram nos pacientes NR em M1 e M2. Portanto, conclui-se que há diferença no perfil das células imunes circulantes em pacientes com regressão e não regressão da rigidez hepática, permitindo, assim, o desenvolvimento de um modelo preditivo de regressão da rigidez hepática após a RVS, devendo ser validado em número maior de pacientes prospectivamente.
Cirrhotic patients with chronic hepatitis C, even after sustained virological response (SVR), should be monitored for the evaluation of liver function and screening of hepatocellular carcinoma (HCC) every six months for life. After treatment and viral clearance, the stage of inflammatory resolution and regression of fibrosis should happen. However, liver examinations by elastography show that 30 to 40% of patients do not exhibit a decrease in liver stiffness. This work was a cohort study in cirrhotic patients whose purpose was to identify immunological factors involved in the regression of liver stiffness in chronic hepatitis C, and characterize possible prognostic value serum biomarkers. The sample universe consisted of 31 cirrhotic patients who underwent leukocyte immunophenotyping, quantification of cytokines / chemokines and metalloproteinase inhibitors (TIMP 1, 2, 3) in the pre-treatment (M1) and in the evaluation of SVR (M2) (retrospective analysis). Inclusion criteria were HCV genotype 1 infection, diagnosis of cirrhosis, absence of comorbidities of infectious, inflammatory or neoplastic origin, non-use of immunosuppressant and confirmation of SVR in M2. Exclusion criteria were: liver transplantation and / or development of nodules or HCC during the follow-up period, absence of elastography examination in M1 or M3 (24 months after SVR), result of liver elastography incompatible with cirrhosis and loss of follow-up. The 16 patients included were again evaluated by immunophenotyping, multiplex analysis and elastography 24 months after SVR (M3) and classified into regressors (R) and non-regressors (NR) (decrease ≥25% stiffness) (prospective analysis). The results from ROC curve, machine learning (ML) and linear discriminant analysis showed that the absolute quantification of TCD4+ lymphocytes is the most important biomarkers for the prediction of the regression (AUC= 0,90). NR patients had levels less than R of stiffness since baseline quantification (M1), whereas NK cells were increased in NR patients at M1 and M2. Therefore, it was concluded that there is a difference in the profile of circulating immune cells in patients with regression and non-regression of liver stiffness, thus allowing the development of a predictive model 35 of regression of liver stiffness after SVR, and should be validated in greater numbers of patients prospectively.
Cirrhotic patients with chronic hepatitis C, even after sustained virological response (SVR), should be monitored for the evaluation of liver function and screening of hepatocellular carcinoma (HCC) every six months for life. After treatment and viral clearance, the stage of inflammatory resolution and regression of fibrosis should happen. However, liver examinations by elastography show that 30 to 40% of patients do not exhibit a decrease in liver stiffness. This work was a cohort study in cirrhotic patients whose purpose was to identify immunological factors involved in the regression of liver stiffness in chronic hepatitis C, and characterize possible prognostic value serum biomarkers. The sample universe consisted of 31 cirrhotic patients who underwent leukocyte immunophenotyping, quantification of cytokines / chemokines and metalloproteinase inhibitors (TIMP 1, 2, 3) in the pre-treatment (M1) and in the evaluation of SVR (M2) (retrospective analysis). Inclusion criteria were HCV genotype 1 infection, diagnosis of cirrhosis, absence of comorbidities of infectious, inflammatory or neoplastic origin, non-use of immunosuppressant and confirmation of SVR in M2. Exclusion criteria were: liver transplantation and / or development of nodules or HCC during the follow-up period, absence of elastography examination in M1 or M3 (24 months after SVR), result of liver elastography incompatible with cirrhosis and loss of follow-up. The 16 patients included were again evaluated by immunophenotyping, multiplex analysis and elastography 24 months after SVR (M3) and classified into regressors (R) and non-regressors (NR) (decrease ≥25% stiffness) (prospective analysis). The results from ROC curve, machine learning (ML) and linear discriminant analysis showed that the absolute quantification of TCD4+ lymphocytes is the most important biomarkers for the prediction of the regression (AUC= 0,90). NR patients had levels less than R of stiffness since baseline quantification (M1), whereas NK cells were increased in NR patients at M1 and M2. Therefore, it was concluded that there is a difference in the profile of circulating immune cells in patients with regression and non-regression of liver stiffness, thus allowing the development of a predictive model 35 of regression of liver stiffness after SVR, and should be validated in greater numbers of patients prospectively.
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Palavras-chave
Cirrose hepática, Elastografia, Hepatite C, Liver cirrhosis, Elastography, Hepatitis C