Dynamic changes in PD-1, TLR3, and TLR4 surface expression on peripheral blood mononuclear cells in chronic hepatitis C patients undergoing peg-IFNalpha-2a plus ribavirin combination therapy / 中华肝脏病杂志
Chinese Journal of Hepatology
; (12): 196-201, 2013.
Artigo
em Chinês
| WPRIM (Pacífico Ocidental)
| ID: wpr-246722
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the dynamic changes in expression of programmed death (PD)-1, Toll-like receptor (TLR)3, and TLR4 on the surface of peripheral blood mononuclear cells (PBMCs) in patients with chronic hepatitis C (CHC) that occur in response to pegylated-interferon alpha-2a (peg-IFNalpha-2a) plus ribavirin (RBV) combination therapy, and to analyze the relation to achievement of sustained virological response (SVR). METHODS Twenty-three CHC patients and 10 healthy controls were enrolled in the study. All CHC patients underwent 48 weeks of combination therapy with peg-IFNalpha-2a (180 microg, subcutaneous injection, once weekly) plus RBV (15 microg/kg, oral, once daily). Total PBMCs were isolated from both groups (CHC patients at treatment week 0, 12, 24, and 48 and post-treatment week 24; controls at enrollment) and subjected to flow cytometric analysis of PD-1, TLR3, and TLR4 surface expression. In addition, serum levels of alanine aminotransferase (ALT) and hepatitis C virus (HCV) RNA levels were analyzed by enzymatic assay and the AmpliPrep/COBAS (Roche) nucleic acid amplification test, respectively. SVR was defined as undetectable levels of HCV RNA at post-treatment week 24. Intergroup differences were assessed by one-way ANOVA.</p><p><b>RESULTS</b>The expression ratios of PD-1, TLR4 and PD-1 TLR4 on PBMCs were significantly higher in CHC patients before therapy than in the healthy controls (45.20 +/- 7.12% vs. 16.82 +/- 4.13%, 58.45 +/- 15.13% vs. 21.09 +/- 2.89%, and 35.54 +/- 7.69% vs. 14.12 +/- 2.89%; all P < 0.05). In contrast, the expression ratios of TLR3 and PD-1TLR3 were slightly, but not significantly, higher in CHC patients before therapy than in the healthy controls (P > 0.05). During the course of peg-IFNalpha-2a plus RBV combination therapy, the expression ratios of PD-1 and TLR4 on PBMCs showed a decreasing trend, while TLR3 expression showed an increasing trend. Furthermore, CHB patients who achieved SVR at post-treatment week 24 had a significantly different expression ratio of PD-1 and TLR3 than those who did not achieve SVR (P < 0.05).</p><p><b>CONCLUSION</b>Surface expression of PD-1, TLR4, and PD-1TLR4 is up-regulated in the total PBMCs of CHC patients. Peg-IFNalpha-2a plus RBV treatment-induced suppression of HCV replication results in a significant reduction in PD-1 and TLR4 expression on the surface of PBMCs, but a remarkably elevated level of TLR3 expression. The dynamic change in PD-1 and TLR3 expression on PBMCs that occurs during antiviral therapy may be related to achievement of SVR.</p>
Texto completo:
Disponível
Contexto em Saúde:
ODS3 - Saúde e Bem-Estar
/
ODS3 - Meta 3.3 Acabar com as doenças tropicais negligenciadas e combater as doenças transmissíveis
/
ODS3 - Meta 3.4 Reduzir as mortes prematuras devido doenças não transmissíveis
Problema de saúde:
Meta 3.3: Acabar com as doenças tropicais negligenciadas e combater as doenças transmissíveis
/
Hepatite
/
Doenças do Sistema Digestório
Base de dados:
WPRIM (Pacífico Ocidental)
Assunto principal:
Polietilenoglicóis
/
Ribavirina
/
Proteínas Recombinantes
/
Estudos de Casos e Controles
/
Resultado do Tratamento
/
Interferon-alfa
/
Hepatite C Crônica
/
Usos Terapêuticos
/
Tratamento Farmacológico
/
Quimioterapia Combinada
Tipo de estudo:
Estudo observacional
/
Fatores de risco
Limite:
Adulto
/
Feminino
/
Humanos
/
Masculino
Idioma:
Chinês
Revista:
Chinese Journal of Hepatology
Ano de publicação:
2013
Tipo de documento:
Artigo