Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5908880 | Infection, Genetics and Evolution | 2015 | 8 Pages |
Abstract
Adefovir dipivoxil (ADV) is used as first-line monotherapy or rescue therapy in chronic hepatitis B (CHB) patients. In this study, we sought to identify nucleotide changes in the reverse transcriptase (RT) of hepatitis B virus (HBV) at baseline and explore their predictive value for ADV antiviral response. Ultra-deep pyrosequencing (UDPS) was utilized to determine HBV genetic variability within the RT region at baseline and during a 48-week ADV therapy. According to the viral load at the end of ADV treatment, all patients were classified into responders (HBV DNA level reduction of ⩾3 log 10 IU/mL) and suboptimal responders (HBV DNA level reduction of <3 log 10 IU/mL). Based on UDPS data at baseline, we identified 11 nucleotide substitutions whose combination frequency was significantly associated with the antiviral response among 36 CHB patients in the study group. However, the baseline distribution and frequency of rt181 and rt236 substitutions known to confer ADV resistance was a poor predictor for the antiviral response. Compared with baseline serum HBeAg, HBV-DNA and ALT levels, the baseline HBV sequence-based model showed higher predictive accuracy for ADV response. In an independent cohort of 31 validation patients with CHB, the sequence-based model provided greater predictive potency than the HBeAg/HBV-DNA/ALT and the HBeAg/HBV-DNA/ALT/sequence combinations. Taken together, we confirm the presence of ADV resistance variants in treatment-naïve patients and firstly unravel the predictive value of the baseline mutations in the HBV RT region for ADV antiviral response.
Keywords
viral responseAdVUDPSnucleoside/nucleotide analoguesTBVHDVCHBSDSORFsETVNASALTROCTDFAUCHCCadefovir dipivoxilASTAlanine aminotransferaseShannon entropystandard deviationsEntecavirReverse transcriptasetelbivudineTenofovirRandom forestAntiviral therapybody mass indexBMIOpen reading framesLAMLamivudineSVMSupport vector machinenegative predictive valuesPositive predictive valuesarea under the curvechronic hepatitis BHBVHepatitis C virusHCVpolymerase chain reactionPCRHIVhuman immunodeficiency virusHepatitis B virus (HBV)Hepatitis D virushepatitis B virusUltra-deep pyrosequencingHepatocellular carcinomareceiver operating characteristic
Related Topics
Life Sciences
Agricultural and Biological Sciences
Ecology, Evolution, Behavior and Systematics
Authors
Yu-Wei Wang, Xuefeng Shan, Yao Huang, Haijun Deng, Wen-Xiang Huang, Da-Zhi Zhang, Juan Chen, Ni Tang, You-Lan Shan, Jin-Jun Guo, Ailong Huang,