title: Novel HBV mutations and their value in predicting efficacy of conventional interferon.
abstract: 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 3730xl 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/mL), P=0.001]. The baseline ALT levels were significantly higher in the HBeAg clearance group (204.72+/-88.65 vs 162.80+/-85.81 IU/L, P<0.05) and HBeAg 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/m2, P<0.05) were prone to acquired biochemical response (BR). PC-W28STOP (ntG1896A) 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 (ntA1726C) and BCP-L134L (ntA1775C/G/T) influenced VR independently. PC-G182C (ntG2357T), PC-S64A/T (ntT2003G/A) and BMI were independent influence factors for HBeAg clearance, HBeAg 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 (ntC2288A), BCP-N118T (ntA1726C), BCP-L134L (ntA1775C/G/T), PC-G182C (ntG2357T) and PC-S64A/T (ntT2003G/A) were novel identified mutations that impacted IFN therapeutic efficacy. These novel mutations could serve as important predictors before conventional IFN treatment.
authors.affiliation: Department of Infectious Diseases, Xiangya Hospital, Central South University, Key Laboratory of Viral Hepatitis of Hunan Province, Changsha, China. dmt3008@163.com.
authors.forename: Da-Xian
authors.initials: DX
authors.lastname: Wu
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Fu
authors.forename: Guo-Zhong
authors.initials: GZ
authors.lastname: Gong
authors.forename: Ke-Wei
authors.initials: KW
authors.lastname: Sun
authors.forename: Huan-Yu
authors.initials: HY
authors.lastname: Gong
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.forename: Juan
authors.initials: J
authors.lastname: Wu
authors.forename: De-Ming
authors.initials: DM
authors.lastname: Tan
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D004279:DNA, Viral / Q000097:blood / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006509:Hepatitis B / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007372:Interferons / Q000009:adverse effects / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D009154:Mutation; D016017:Odds Ratio; D010641:Phenotype; D011237:Predictive Value of Tests; D012372:ROC Curve; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D007372:Interferons; D000410:Alanine Transaminase