Original Article—Liver, Pancreas, and Biliary Tract

Journal of Gastroenterology

, Volume 46, Issue 4, pp 501-509

First online:

High ability to predict the treatment outcome of peginterferon and ribavirin combination therapy based on the reduction in HCV RNA levels at 4 weeks after starting therapy and amino acid substitutions in the hepatitis C virus in patients infected with HCV genotype 1b

  • Hidenori ToyodaAffiliated withDepartment of Gastroenterology, Ogaki Municipal Hospital Email author 
  • , Takashi KumadaAffiliated withDepartment of Gastroenterology, Ogaki Municipal Hospital
  • , Seiki KiriyamaAffiliated withDepartment of Gastroenterology, Ogaki Municipal Hospital
  • , Makoto TanikawaAffiliated withDepartment of Gastroenterology, Ogaki Municipal Hospital
  • , Yasuhiro HisanagaAffiliated withDepartment of Gastroenterology, Ogaki Municipal Hospital
  • , Akira KanamoriAffiliated withDepartment of Gastroenterology, Ogaki Municipal Hospital
  • , Toshifumi TadaAffiliated withDepartment of Gastroenterology, Ogaki Municipal Hospital
  • , Takahiro ArakawaAffiliated withDepartment of Gastroenterology, Ogaki Municipal Hospital
  • , Masashi FujimoriAffiliated withDepartment of Gastroenterology, Ogaki Municipal Hospital
    • , Takuro NiinomiAffiliated withDepartment of Gastroenterology, Ogaki Municipal Hospital
    • , Naoto AndoAffiliated withDepartment of Gastroenterology, Ogaki Municipal Hospital
    • , Satoshi YasudaAffiliated withDepartment of Gastroenterology, Ogaki Municipal Hospital
    • , Keisuke SakaiAffiliated withDepartment of Gastroenterology, Ogaki Municipal Hospital
    • , Jun KimuraAffiliated withDepartment of Gastroenterology, Ogaki Municipal Hospital

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Abstract

Background

The ability to predict the outcome of peginterferon (PEG-IFN) and ribavirin combination therapy based on the reduction in hepatitis C virus (HCV) RNA levels at 4 weeks after starting the therapy and amino acid substitutions in HCV was to be confirmed.

Methods

We measured the reduction in HCV RNA levels at 4 weeks after starting the combination therapy, as well as examining amino acid substitutions at residue 70 in the HCV core and within the interferon sensitivity-determining region (ISDR) of HCV non-structural protein 5A (NS5A), for 101 patients infected with HCV genotype 1b. The ability of these factors to predict a sustained virologic response (SVR) was analyzed.

Results

When a 3 log10 reduction in HCV RNA levels at 4 weeks after starting therapy was set as the cut-off value, an SVR was achieved in 37 of the 46 patients (80.4%) with a ≥3 log10 decrease and in 4 of the 55 patients (7.3%) with a <3 log10 decrease. All 4 patients who achieved an SVR despite a <3 log10 reduction in HCV RNA levels at 4 weeks had an arginine at residue 70 in the HCV core and a non-wild-type sequence for the ISDR of HCV NS5A.

Conclusion

A ≥3 log10 reduction in HCV RNA levels at 4 weeks after starting therapy indicates that a patient has a high likelihood of achieving an SVR as a final outcome. Additional information on the amino acid substitutions at residue 70 in the HCV core and within NS5A-ISDR will further increase the ability to predict a clinical response.

Keywords

Chronic hepatitis C Four weeks Peginterferon Reduction in HCV RNA Response-guided therapy Ribavirin