title: Predictive factors of early and sustained responses to peginterferon plus ribavirin combination therapy in Japanese patients infected with hepatitis C virus genotype 1b: amino acid substitutions in the core region and low-density lipoprotein cholesterol levels.
abstract: OBJECTIVE
  We showed previously that amino acid (aa) substitutions in the HCV core region (HCV-CR) are predictors of non-virological response (NVR) to peginterferon (PEG-IFN) plus ribavirin (RBV) therapy. Here, we determined the predictive factors of sustained virological response (SVR) and early virologic response (EVR) to this treatment.
  
  
  METHODS
  We evaluated the response to 48-week PEG-IFN-RBV therapy in 114 Japanese adults infected with HCV genotype 1b and determined the predictors of EVR and SVR.
  
  
  RESULTS
  EVR was achieved by 70% and SVR by 45% of patients. 64% of patients who achieved EVR also showed SVR, while none of non-EVR achieved SVR. Multivariate analysis identified low-density lipoprotein cholesterol (LDL-C) (>or=86 mg/dl), aa substitutions in HCV-CR (double-wild-type; arginine at aa 70/leucine at aa 91), gamma-glutamyl transpeptidase (GGT) (<109 IU/l), RBV dose (>or=11.0mg/kg), and leukocyte count (>or=4500/mm3) as significant determinants of EVR, and aa substitutions in HCV-CR (double-wild-type), LDL-C (>or=86 mg/dl), male gender, ICG R15 (<10%), GGT (<109 IU/l), and RBV dose (>or=11.0 mg/kg) as determinants of SVR. Prediction of response to therapy based on combination of these factors had high sensitivity, specificity, positive, and negative predictive values.
  
  
  CONCLUSIONS
  Our study identified aa substitutions in the core region and serum LDL-C as predictors of response to PEG-IFN-RBV therapy in Japanese patients infected with HCV genotype 1b.
authors.affiliation: Department of Hepatology, Toranomon Hospital, Tokyo, Japan. akuta-gi@umin.ac.jp
authors.forename: Norio
authors.initials: N
authors.lastname: Akuta
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Suzuki
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kawamura
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yatsuji
authors.forename: Hitomi
authors.initials: H
authors.lastname: Sezaki
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hosaka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Mariko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Arase
authors.forename: Kenji
authors.initials: K
authors.lastname: Ikeda
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D008078:Cholesterol, LDL / Q000097:blood / Q000737:chemistry / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D006526:Hepatitis C / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use*; D007564:Japan; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011994:Recombinant Proteins; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use*; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D014758:Viral Core Proteins / Q000097:blood / Q000737:chemistry*
chemical_list: D000998:Antiviral Agents; D008078:Cholesterol, LDL; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014758:Viral Core Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a