Influência dos antivirais de ação direta na resistência insulínica, nos marcadores de fibrose e função hepática na cirrose por Hepatite C
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Data
2018-11-14
Autores
Andrade, Vanessa Gutierrez de
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Universidade Estadual Paulista (Unesp)
Resumo
Introdução: O Vírus da Hepatite C está associado a manifestações extra-hepáticas, dentre elas a resistência à insulina (RI). Estudos baseados em Interferon (IFN) e Ribavirina (RBV) mostraram uma melhora da RI e da regressão de fibrose associada à Resposta Virológica Sustentada (RVS), mesmo em pacientes cirróticos.As evidências são incertas se isso ocorre com os Antivirais de Ação Direta (AADs). Objetivos: Avaliar a influência da RVS em cirróticos infectados pelo vírus da hepatite C (VHC) tratados com os AADs na RI, nos Lipídes Séricos, nos marcadores indiretos de atividade inflamatória, nos marcadores indiretos de fibrose hepática e nos escores de avaliação de função hepática. Metodologia: Estudo prospectivo longitudinal realizado no Ambulatório de Hepatites Virais da disciplina de Gastroenterologia do Hospital das Clínicas da Faculdade de Medicina de Botucatu em dois períodos: no início do tratamento (t-base) e na décima segunda semana após o fim do tratamento (t-RVS). Critérios de Inclusão: infecção pelo VHC (RNA-VHC positivo), idade ≥ 18 anos, conclusão da terapia com AADs, presença de cirrose hepática e amostras coletadas no t-base e t-RVS. Critérios de Exclusão: presença de coinfecção VHB/HIV, Carcinoma Hepatocelular no início do estudo ou no t-RVS, pacientes transplantados (fígado/rim). Para confirmação da cirrose utilizou-se a elastografia hepática ou biópsia (METAVIR), como também a clínica ou exames de imagem. Para avaliação indireta da fibrose hepática, utilizou-se as seguintes fórmulas: APRI = Valor de AST (UI/L) / Limite Superior Normal de AST (UI/L)/Contagem de Plaquetas (109) × 100 e FIB4 = Idade (anos) × AST (UI/L)/Contagem de Plaquetas (109) × √ALT (UI/L). Para a avaliação dos escores de função hepática, utilizou-se a pontuação de Child-Pugh e o MELD. O HOMA-IR foi calculado como insulinemia de jejum (μU/mL) x glicemia de jejum (mmol/l)/22,5).Foi realizado elastografia hepática no baseline e após a RVS. Realizou-se a análise estatística descritiva e modelo linear generalizado assumindo-se distribuição de Poisson e distribuição gama com função de ligação log. O valor de P considerado significativo foi < 0,05. Resultados: De 141 pacientes, foram incluídos 117. Os resultados do MELD, APRI e FIB4 no t-base/t-RVS foram 10,3±3,04/9,52±3,14 (p=0,0078); 2,19±2,01/0,93±1,02 (p<0,0001) e 5,61±3,45/3,86±3,14 (p=0,0001), respectivamente.Os resultados de Ferritina (ng/mLl), Alfa Feto Proteína (ng/mL), CT (mg/dL), LDL (mg/dL) e TG (mg/dL) e HOMA-IR no t-base / t-RVS foram: 446,47±492,94/182,67 173,65 (p<0,0001); 19,62±57,76/5,39±3,97 (p=0,0105); 143,25±33,69/153,81±33,78 (p=0,0010); 75,69±29,97/86,03±31,22 (p=0,0036) e 98,19± 44,97/96,59±50,36 (p=0,7432), 4,88±4,11/5,25±4,9 (p=0,685), respectivamente.Os resultados de Elastografia no t-base/t-RVS foram:27,82 ± 9,59 / 19,26 ± 9,72 (p<0,001).Conclusão: Os escores de Avaliação Indireta da Fibrose Hepática e os de avaliação da Função Hepática melhoraram significativamente em pacientes cirróticos com RVS tratados com AADs. A Ferritina e Alfa Feto Proteína Séricas diminuíram significativamente, e o CT e LDL aumentaram significativamente. Nos nivéis séricos de TG não foram observadas mudanças significativas. Houve uam redução significativa da média de Elastografia Hepática na RVS. A média do HOMA-IR aumentou na RVS, porém sem significância estatística.
Introduction: Hepatitis C virus is associated with extrahepatic manifestations, including insulin resistance (IR). Studies based on Interferon (IFN) and Ribavirin (RBV) have shown an improvement in IR and fibrosis regression associated with Sustained Virological Response (SVR), even in cirrhotic patients. This evidence is uncertain if this occurs with Direct Action Antivirals (DAAs). Objective: To evaluate the influence of SVR on hepatitis C virus (HCV) infected cirrhotic patients treated with DAAs in IR, Serum Lipids, indirect markers of inflammatory activity, indirect markers of hepatic fibrosis and evaluation scores of hepatic function. Methods: Prospective longitudinal study conducted at the Viral Hepatitis Outpatient Clinic of the Gastroenterology Department of the Clinical Hospital of Botucatu Medical School in two periods: at the beginning of treatment (t-base) and at the twelfth week after the end of treatment (t-SVR). Inclusion Criteria: HCV infection (age-positive HCV RNA), age ≥ 18 years, completion of DAAs therapy, presence of liver cirrhosis and samples collected at t-base and t-SVR. Exclusion Criteria: presence of HBV / HIV coinfection, Hepatocellular Carcinoma at baseline or in t-SVR, transplanted patients (liver / kidney). To confirm cirrhosis, hepatic elastography or biopsy (METAVIR) was performed, as were clinical or imaging tests. The following formulas were used for the indirect evaluation of hepatic fibrosis: APRI = AST (UI / L) / AST (UI / L) Normal Limit / Platelet Count (109) × 100 and FIB4 = Age) × AST (IU / L) / Platelet Count (109) × √ALT (IU / L). For the evaluation of liver function scores, Child-Pugh score and MELD were used. HOMA-IR was calculated as fasting insulin (μU / mL) x fasting blood glucose (mmol / l) / 22.5).Hepatic elastography was performed at baseline and after SVR. Descriptive statistical analysis and generalized linear model were performed assuming Poisson distribution and gamma distribution with log binding function. The P value considered significant was < 0.05. Results: Of 141 patients, 117 were included. The results of MELD, APRI and FIB4 in t-base / t-SVR were 10.3 ± 3.04 / 9.52 ± 3.14 (p = 0.0078); 2.19 ± 2.01 / 0.93 ± 1.02 (p <0.0001) and 5.61 ± 3.45 / 3.86 ± 3.14 (p = 0.0001), respectively. The results of Ferritin (ng / mL), Alfa-Feto Protein (ng / mL), CT (mg / dL), LDL (mg / dL) and TG RVS were: 446.47 ± 492.94 / 182.67 173.65 (p <0.0001); 19.62 ± 57.76 / 5.39 ± 3.97 (p = 0.0105); 143.25 ± 33.69 / 153.81 ± 33.78 (p = 0.0010); 75.69 ± 29.97 / 86.03 ± 31.22 (p = 0.0036) and 98.19 ± 44.97 / 96.59 ± 50.36 (p = 0.7432), 4.88 ± 4.11 / 5.25 ± 4.9 (p = 0.685), respectively.The results of T-base / t-SVR Elastography were: 27.82 ± 9.59 / 19.26 ± 9.72 (p <0.001). Conclusion: Indirect Hepatic Fibrosis Assessment and Hepatic Function evaluation scores were significantly improved in cirrhotic patients with SVR treated with DAAs. Serum Ferritin and Alpha Fetus Protein decreased significantly, and TC and LDL increased significantly. No significant changes were observed in serum TG levels. There was a significant reduction in the mean of Hepatic Elastography in SVR.The mean HOMA-IR increased in SVR, but without statistical significance.
Introduction: Hepatitis C virus is associated with extrahepatic manifestations, including insulin resistance (IR). Studies based on Interferon (IFN) and Ribavirin (RBV) have shown an improvement in IR and fibrosis regression associated with Sustained Virological Response (SVR), even in cirrhotic patients. This evidence is uncertain if this occurs with Direct Action Antivirals (DAAs). Objective: To evaluate the influence of SVR on hepatitis C virus (HCV) infected cirrhotic patients treated with DAAs in IR, Serum Lipids, indirect markers of inflammatory activity, indirect markers of hepatic fibrosis and evaluation scores of hepatic function. Methods: Prospective longitudinal study conducted at the Viral Hepatitis Outpatient Clinic of the Gastroenterology Department of the Clinical Hospital of Botucatu Medical School in two periods: at the beginning of treatment (t-base) and at the twelfth week after the end of treatment (t-SVR). Inclusion Criteria: HCV infection (age-positive HCV RNA), age ≥ 18 years, completion of DAAs therapy, presence of liver cirrhosis and samples collected at t-base and t-SVR. Exclusion Criteria: presence of HBV / HIV coinfection, Hepatocellular Carcinoma at baseline or in t-SVR, transplanted patients (liver / kidney). To confirm cirrhosis, hepatic elastography or biopsy (METAVIR) was performed, as were clinical or imaging tests. The following formulas were used for the indirect evaluation of hepatic fibrosis: APRI = AST (UI / L) / AST (UI / L) Normal Limit / Platelet Count (109) × 100 and FIB4 = Age) × AST (IU / L) / Platelet Count (109) × √ALT (IU / L). For the evaluation of liver function scores, Child-Pugh score and MELD were used. HOMA-IR was calculated as fasting insulin (μU / mL) x fasting blood glucose (mmol / l) / 22.5).Hepatic elastography was performed at baseline and after SVR. Descriptive statistical analysis and generalized linear model were performed assuming Poisson distribution and gamma distribution with log binding function. The P value considered significant was < 0.05. Results: Of 141 patients, 117 were included. The results of MELD, APRI and FIB4 in t-base / t-SVR were 10.3 ± 3.04 / 9.52 ± 3.14 (p = 0.0078); 2.19 ± 2.01 / 0.93 ± 1.02 (p <0.0001) and 5.61 ± 3.45 / 3.86 ± 3.14 (p = 0.0001), respectively. The results of Ferritin (ng / mL), Alfa-Feto Protein (ng / mL), CT (mg / dL), LDL (mg / dL) and TG RVS were: 446.47 ± 492.94 / 182.67 173.65 (p <0.0001); 19.62 ± 57.76 / 5.39 ± 3.97 (p = 0.0105); 143.25 ± 33.69 / 153.81 ± 33.78 (p = 0.0010); 75.69 ± 29.97 / 86.03 ± 31.22 (p = 0.0036) and 98.19 ± 44.97 / 96.59 ± 50.36 (p = 0.7432), 4.88 ± 4.11 / 5.25 ± 4.9 (p = 0.685), respectively.The results of T-base / t-SVR Elastography were: 27.82 ± 9.59 / 19.26 ± 9.72 (p <0.001). Conclusion: Indirect Hepatic Fibrosis Assessment and Hepatic Function evaluation scores were significantly improved in cirrhotic patients with SVR treated with DAAs. Serum Ferritin and Alpha Fetus Protein decreased significantly, and TC and LDL increased significantly. No significant changes were observed in serum TG levels. There was a significant reduction in the mean of Hepatic Elastography in SVR.The mean HOMA-IR increased in SVR, but without statistical significance.
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Palavras-chave
Hepatite C, Antivirais de ação direta, APRI, FIB-4, Hepatitis C, Direct action anti viral, APRI, FIB-4