Serum microRNA-122 level correlates with virologic responses to pegylated interferon therapy in chronic hepatitis C
Journal
Proceedings of the National Academy of Sciences of the United States of America
Journal Volume
110
Journal Issue
19
Pages
7844-7849
Date Issued
2013
Author(s)
Abstract
MicroRNA-122 (miR-122) facilitates hepatitis C virus replication in vitro. SerummiR-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 Cwho 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.
SDGs
Other Subjects
gamma glutamyltransferase; microRNA 122; peginterferon alpha2a; peginterferon alpha2b; ribavirin; triacylglycerol; adult; article; body mass; female; genotype; hepatitis C; human; human tissue; major clinical study; male; priority journal; treatment response
Publisher
National Academy of Sciences
Type
journal article