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

J Hepatol. 2007 Mar;46(3):403-10. doi: 10.1016/j.jhep.2006.09.019. Epub 2006 Nov 7.

Abstract

Background/aims: 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amino Acid Substitution*
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Cholesterol, LDL / blood
  • Cholesterol, LDL / chemistry
  • Cholesterol, LDL / genetics*
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hepacivirus / drug effects
  • Hepacivirus / genetics*
  • Hepatitis C / blood
  • Hepatitis C / drug therapy*
  • Hepatitis C / genetics
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / pharmacology
  • Interferon-alpha / therapeutic use*
  • Japan
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Polyethylene Glycols / pharmacology
  • Polyethylene Glycols / therapeutic use*
  • Predictive Value of Tests
  • Recombinant Proteins
  • Ribavirin / pharmacology
  • Ribavirin / therapeutic use*
  • Sensitivity and Specificity
  • Treatment Outcome
  • Viral Core Proteins / blood
  • Viral Core Proteins / chemistry*

Substances

  • Antiviral Agents
  • Cholesterol, LDL
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Viral Core Proteins
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2a