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Proc Natl Acad Sci U S A ; 110(19): 7844-9, 2013 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-23613588

RESUMO

MicroRNA-122 (miR-122) facilitates hepatitis C virus replication in vitro. Serum miR-122 has been implicated as a biomarker for various liver diseases; however, its role in chronic hepatitis C remains unclear. To address this issue, 126 patients with chronic hepatitis C who completed pegylated IFN plus ribavirin therapy with sustained virologic response (SVR) or nonresponse (NR) were retrospectively included, and their pretreatment clinical profiles and treatment responses were collected. Serum miR-122 was quantified before and during treatment. Another 51 patients in SVR and NR groups were prospectively enrolled for validation. Serum miR-122 was found to be a surrogate for hepatic miR-122 and positively correlated with hepatic necroinflammation. Patients who showed complete early virologic response and SVR had significantly higher pretreatment serum miR-122 levels than those with NR (P = 0.001 and P = 0.008, respectively), especially in subgroups of patients with hepatitis C virus genotype 2 and IL-28B rs8099917 TT genotype. Patients with IL-28B TT genotype had significantly better treatment responses and higher pretreatment serum miR-122 level than those with GT or GG genotypes. Univariate analysis showed that pretreatment body mass index, γ-glutamyl transpeptidase, triglyceride, IL-28B TT genotype, and serum miR-122 are predictors for SVR. Multivariate analysis specifically in IL-28B TT genotype demonstrated that pretreatment serum miR-122 independently predicted SVR. The validation cohort confirmed a significantly greater pretreatment serum miR-122 level in patients with SVR compared with NR (P = 0.025). In conclusion, serum miR-122 may serve as a surrogate of hepatic miR-122, and a higher pretreatment serum miR-122 level can help predict virologic responses to pegylated IFN plus ribavirin therapy.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/sangue , Interferon-alfa/uso terapêutico , MicroRNAs/sangue , Polietilenoglicóis/uso terapêutico , Adulto , Idoso , Biópsia , Índice de Massa Corporal , Estudos de Coortes , Feminino , Genótipo , Hepatite C Crônica/tratamento farmacológico , Humanos , Fígado/metabolismo , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Análise Multivariada , Proteínas Recombinantes/uso terapêutico , Ribavirina/administração & dosagem , Fatores de Tempo , Resultado do Tratamento
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