Prediction of Virological Response by Pretreatment Hepatitis B Virus Reverse Transcriptase Quasispecies Heterogeneity: the advantage of using Next Generation Sequencing.

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases

PubMedID: 25882357

Han Y, Gong L, Sheng J, Liu F, Li XH, Chen L, Yu M, Gong QM, Hao P, Zhang XX. Prediction of Virological Response by Pretreatment Hepatitis B Virus Reverse Transcriptase Quasispecies Heterogeneity: the advantage of using Next Generation Sequencing. Clin Microbiol Infect. 2015;.
Prediction of antiviral efficacy prior to treatment remains largely unavailable. We had previously demonstrated the clinical value of on-treatment hepatitis B virus (HBV) reverse transcriptase (RT) quasispecies (QS) evolution patterns. In this study, we aimed to elucidate the prediction relevance of pretreatment HBV RT QS characteristic by comparing the performance of Next Generation Sequencing (NGS) and clone base Sanger sequencing (CBS). Thirty six lamivudine treated patients were retrospectively studied, including eighteen responders and eighteen non-responders. CBS and NGS data of pretreatment serum HBV were used to generate RT QS genetic complexity and diversity scores according to our previous studies. The ability of both methods to predict responsiveness was evaluated by receiver-operator characteristic (ROC) curves. A cut-off value was generated based on its ability of prediction. Responders had significantly higher pretreatment RT QS genetic complexity and diversity (in the first two parts, which overlapped with S gene, both in nucleotide and amino acid level) than non-responders by NGS based testing. NGS based algorithms predicted response better than CBS in the ROC curve analysis. The mean distance of the second contig had the highest area under curve (AUC) value. When the cut-off value was set to be 0. 007186, the difference between survival curves was significant (p=0. 0090). Pretreatment HBV RT QS heterogeneity in overlapping region of RT and S gene could be a predictor of antiviral efficacy. NGS improves its predictions of virological outcomes relative to CBS algorithms. This may give important implication to the clinical management of subjects chronically infected with HBV.