RESUMO
BACKGROUND: Egypt has the highest prevalence of a difficult to treat chronic hepatitis C virus (HCV), genotype 4. Pretreatment factors could guide individualization of therapy which aids in treatment optimization and interleukin IL28B gene polymorphism has been shown to closely relate to HCV treatment response. Polymorphisms in genes encoding inhibitors of T-cell response, which have role in disease progression as Programmed Cell Death 1 (PD-1), and Cytotoxic T-Lymphocytes Antigen-4 (CTLA-4), could be candidate markers predicting treatment response. METHODS: This cohort study consisted of 200 chronic HCV genotype 4 infected patients treated with PegIFN α-2a and RBV in 2 hepatology centers. Genotyping of the polymorphisms in the IL28B gene region (rs12979860), PD1.3 (rs11568821) and CTLA-4 (rs231775) was performed on DNA collected from each patient using TaqMan® genotyping assay. Groups were classified according to response into sustained virological responders (SVR), or non-responders (NR). A multivariate logistic regression analysis was used to identify potential markers, host pretreatment clinical and viral predictive factors including viral load, insulin resistance, and alpha fetoprotein (AFP) related to treatment response. RESULTS: Our results showed that in a multivariate analyses IL28B C/C genotype was the most significant predictor for SVR (OR = 10.86; p<0.0001) followed by AFP (OR = 0.915; p = 0.001) then CTLA-4/G genotypes (OR = 1.948; p = 0.022). However, PD-1.3/A genotypes and platelets count were significantly related to response in univariate analysis only (OR = 1.973; p = 0.023; OR = 1.007; p = 0.009 respectively). CONCLUSION: IL28B SNP, AFP level, and CTLA-4 SNP could be used in conjunction to predict treatment response in HCV genotype 4 infected Egyptian patients.
Assuntos
Biomarcadores/metabolismo , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/genética , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Polimorfismo de Nucleotídeo Único/genética , Ribavirina/uso terapêutico , Adulto , Antivirais/uso terapêutico , Antígeno CTLA-4/genética , Quimioterapia Combinada , Feminino , Hepacivirus/classificação , Hepatite C Crônica/imunologia , Hepatite C Crônica/virologia , Humanos , Interferons , Interleucinas/genética , Masculino , Reação em Cadeia da Polimerase , Receptor de Morte Celular Programada 1/genética , Curva ROC , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento , Carga ViralRESUMO
OBJECTIVE: Highlighting the apelin system would present a new therapeutic target for liver disease. Apelin; endogenous ligand for the orphan receptor APJ, was recently suggested to be associated with fibrosis progression and cirrhosis in addition to insulin resistance (IR) and inflammation. The present study was conducted to evaluate blood apelin level changes among 73 chronic hepatitis C (CHC) Egyptian patients and if associated with body mass index (BMI), IR, and tumor necrosis factor-alpha (TNF-α). Serum apelin levels were significantly higher in patients with CHC with median value (3.25) when compared with controls (1.11), at P < 0.0001, with significant apelin variations among asymptomatic carriers (ASC), fibrosis, and cirrhosis patients, and also among obese and nonobese patients. Multiple regression analysis depicted that BMI, triglycerides, and total cholesterol were independent correlation factors to apelin levels, whereas TNF-α was found to be significantly negatively correlated to adjusted apelin in CHC patients (r = -0.5944, P < 0.0001). IR was positively correlated to adjusted apelin in CHC patients (r = 0.2663, P < 0.05). CONCLUSION: Apelin level varies among stages of CHC, which may contribute to fibrosis progression. In addition, obesity and IR could act as comorbid factors affecting apelin level in patients with CHC.