BACKGROUND: Accumulating studies assessing the impacts of hot spot mutations on conventional interferon(IFN) efficacy come to discrepant conclusions; studies regarding the mutations in S and RT regions are also unclear. The present study aimed to evaluate the impacts of HBV mutations on the efficacy of conventional IFN. METHODS: A total of 126 patients who received conventional IFN treatment for 48 weeks were enrolled. Biochemical and serological parameters were routinely tested. The sequences of HBV from 78 serum samples were amplified by nested-PCR; mutations were identified with sequence scanner V1.0 after ABI 3730 xl direct sequencing, HBV genotypes were determined according to RT gene sequences utilizing NCBI Genotyping Tool which was based on phylogenetic analysis.RESULTS: The baseline DNA levels of virological response(VR) group were significantly lower than those of no VR group [7.13±0.76 vs 7.69±0.56 lg(copies/m L), P=0.001]. The baseline ALT levels were significantly higher in the HBe Ag clearance group(204.72±88.65 vs 162.80±85.81 IU/L, P<0.05) andHBe Ag seroconversion group(204.89 ±95.68 vs 166.75±84.43 IU/L, P<0.05). Females and lower BMI levels(20.01±2.33 vs 21.65±3.66 kg/m~2, P<0.05) were prone to acquired biochemical response(BR). PC-W28STOP(ntG 1896A) was significantly higher in the combined response(CR) group than that in the no CR group(91.7% vs 39.7%, P=0.001). Multivariate logistic regression analysis showed that baseline DNA, PC-P159T(ntC2288A), BCP-N118T(ntA 1726C) and BCP-L134L(ntA 1775C/G/T) influenced VR independently. PC-G182C(nt G2357T), PC-S64A/T(nt T2003G/A) and BMI were independent influence factors for HBe Ag clearance, HBe Ag seroconversion and BR, respectively. The new predicting model concluded that baseline DNA and new mutations for VR were established successfully, and ROC analysis showed that AUC was 0.842(P<0.001) with a sensitivity of 0.652 and a specificity of 0.933.CONCLUSIONS: PC-P159T(ntC 2288A), BCP-N118T(ntA 1726C), BCP-L134L(nt A1775C/G/T), PC-G182C(nt G2357T) and PCS64A/T(nt T2003G/A) were novel identified mutations that impacted IFN therapeutic efficacy. These novel mutations could serve as important predictors before conventional IFN treatment. BACKGROUND: Accumulating studies assessing the impacts of hot spot mutations on conventional interferon (IFN) efficacy come to discrepant conclusions; studies regarding the mutations in S and RT regions are also unclear. The present study aimed to evaluate the impacts of HBV mutations on the efficacy of conventional IFN. METHODS: A total of 126 patients who previously acquired IFN treatment for 48 weeks were enrolled. Biochemical and serological parameters were routinely tested. The sequences of HBV from 78 serum samples were amplified by nested-PCR; mutations were identified with sequence scanner V1.0 after ABI 3730 xl direct sequencing, HBV genotypes were determined according to RT gene sequences utilizing NCBI Genotyping Tool which was based on phylogenetic analysis .RESULTS: The baseline DNA levels of virological response (VR) group were significantly lower than those of no VR group [7.13 ± 0.76 vs 7.69 ± 0.56 lg (copies / m L), P = 0.001]. The baseline ALT levels were significantly higher in the HBe Ag clearance group (204.72 ± 88.65 vs 162.80 ± 85.81 IU / L, P <0.05) and the HBe Ag seroconversion group (204.89 ± 95.68 vs 166.75 ± 84.43 IU / L, P <0.05) ± 2.33 vs 21.65 ± 3.66 kg / m 2, P <0.05) were prone to acquired biochemical response (BR). PC-W28STOP (ntG 1896A) was significantly higher in the combined response (CR) group than that in the no CR Multivariate logistic regression analysis showed that baseline DNA, PC-P159T (ntC2288A), BCP-N118T (ntA1726C) and BCP-L134L (ntA1775C / G / T) influenced VR (nt G2357T), PC-S64A / T (nt T2003G / A) and BMI were independently influenced factors for HBe Ag clearance, HBe Ag seroconversion and BR, respectively. The new predicting model that that baseline DNA and new mutations for VR were established successfully, and ROC analysis showed that AUC was 0.842 (P <0.001) with a sensitivity of 0.652 and a specificity of 0.933.CONCLUSIONS: PC-P159T (ntC 2288A), BCP- N118T C), BCP-These novel mutations could serve as important predictors before conventional IFN treatment. L134L (nt A1775C / G / T), PC-G182C (nt G2357T) and PCS64A / T