Plasma microRNA profile as a predictor of early virological response to interferon treatment in chronic hepatitis B patients

Xiaonan Zhang, Cuncun Chen, Min Wu, Liang Chen, Jiming Zhang, Xinxin Zhang, Zhanqin Zhang, Jingdi Wu, Jiefei Wang, Xiaorong Chen, Tao Huang, Lixiang Chen, Zhenghong Yuan

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

BACKGROUND: Interferon (IFN) and pegylated interferon (PEG-IFN) treatment of chronic hepatitis B leads to a sustained virological response in a limited proportion of patients and has considerable side effects. To find novel markers associated with prognosis of IFN therapy, we investigated whether a pretreatment plasma microRNA profile could be used to predict early virological response to IFN.

METHODS: We performed microRNA microarray analysis of plasma samples from 94 patients with chronic hepatitis B who received IFN therapy. The microRNA profiles from 13 liver biopsy samples were also measured. The OneR feature ranking and incremental feature selection method were used to rank and optimize the number of features in the model. Support vector machine prediction engine and jack-knife cross-validation were used to generate and evaluate the prediction model.

RESULTS: The optimized model consisting of 11 microRNAs yielded a 74.2% overall accuracy in the training group and was independently confirmed in the test group (71.4% accuracy). Univariate and multivariate logistic regression analyses confirmed its independent association with early virological response (OR=7.35; P=2.12×10(-5)). Combining the microRNA profile with the alanine aminotransferase level improved the overall accuracy from 73.4% to 77.3%. Co-transfection of an HBV replicative construct with microRNA mimics revealed that let-7f, miR-939 and miR-638 were functionally associated with the HBV life cycle.

CONCLUSIONS: The 11 microRNA signatures in plasma, together with basic clinical variables, might provide an accurate method to assist in medication decisions and improve the overall sustained response to IFN treatment.

Original languageEnglish
Pages (from-to)1243-1253
Number of pages11
JournalAntiviral Therapy
Volume17
Issue number7
DOIs
Publication statusPublished - 2012
Externally publishedYes

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