Outcome and Early Viral Dynamics with Viral Mutation in PEG-IFN/RBV Therapy for Chronic Hepatitis in Patients with High Viral Loads of Serum HCV RNA Genotype 1b

We investigated whether sustained virological response (SVR) and non-SVR by chronic hepatitis C patients to pegylated interferon plus ribavirin (PEG-IFN/RBV) combination therapy are distinguishable by viral factors such as the IFN/RBV resistance-determining region (IRRDR) and by on-treatment factors through new indices such as the rebound index (RI). The first RI (RI-1st; the viral load at week 1 divided by the viral load at 24 h) and the second RI (RI-2nd; the viral load at week 2 divided by the viral load at 24 h) were calculated. The subject patients were divided into 3 groups based on RI-1st and RI-2nd: an RI-A group (RI-1st ≤1.0), an RI-B group (RI-1st >1.0 and RI-2nd <0.7) and an RI-C group (RI-1st >1.0 and RI-2nd ≧0.7). The SVR rate was 71.4% (10/14) in the RI-A group, 46.2% (6/13) in the RI-B group and 20.0% (3/15) in the RI-C group (p = 0.005 between the RI-A group and the RI-C group). In IRRDR ≧6 and IRRDR ≤5 the SVR rate was 81.3% (13/16) and 23.1% (6/26) (p = 0.0002), respectively. By combining RI and IRRDR as a predicting factor, the SVR rate was 87.5% (7/8) in the RI-A group (≧6 mutations in the IRRDR) and 7.7% (1/13) in the RI-C group (≤5 IRRDR mutations) (p = 0.0003).

[1]  H. Nomura,et al.  Effective prediction of outcome of combination therapy with pegylated interferon alpha 2b plus ribavirin in Japanese patients with genotype-1 chronic hepatitis C using early viral kinetics and new indices , 2009, Journal of Gastroenterology.

[2]  M. Nagano-Fujii,et al.  Sequence variation in hepatitis C virus nonstructural protein 5A predicts clinical outcome of pegylated interferon/ribavirin combination therapy , 2008, Hepatology.

[3]  M. Kudo,et al.  Usefulness of a New Immunoradiometric Assay of HCV Core Antigen to Predict Virological Response during PEG-IFN/RBV Combination Therapy for Chronic Hepatitis with High Viral Load of Serum HCV RNA Genotype 1b , 2008, Intervirology.

[4]  Yoshiyuki Suzuki,et al.  Prediction of Response to Pegylated Interferon and Ribavirin in Hepatitis C by Polymorphisms in the Viral Core Protein and Very Early Dynamics of Viremia , 2007, Intervirology.

[5]  M. Kurosaki,et al.  Pharmacokinetics and enhanced PKR response in patients with chronic hepatitis C treated with pegylated interferon alpha‐2b and ribavirin , 2007, Journal of viral hepatitis.

[6]  M. Silva,et al.  A randomised trial to compare the pharmacokinetic, pharmacodynamic, and antiviral effects of peginterferon alfa-2b and peginterferon alfa-2a in patients with chronic hepatitis C (COMPARE). , 2006, Journal of hepatology.

[7]  Hideji Nakamura Early prediction of sustained viral responder and non-responder during interferon and ribavirin combination therapy in chronic hepatitis C. , 2005, Hepatology Research.

[8]  M. Kurosaki,et al.  A Comparison of the Exponential Decay Slope between PEG-IFN alfa-2b/Ribavirin and IFN alfa-2b/Ribavirin Combination Therapy in Patients with Chronic Hepatitis C Genotype 1b Infection and a High Viral Load , 2004, Intervirology.

[9]  P. Ferenci Predictors of response to therapy for chronic hepatitis C. , 2004, Seminars in liver disease.

[10]  G. Davis Monitoring of viral levels during therapy of hepatitis C , 2002, Hepatology.

[11]  Dieter Häussinger,et al.  Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. , 2002, The New England journal of medicine.

[12]  M. Buti,et al.  Viral kinetics in genotype 1 chronic hepatitis C patients during therapy with 2 different doses of peginterferon alfa‐2b plus ribavirin , 2002, Hepatology.

[13]  Kenneth Koury,et al.  For Personal Use. Only Reproduce with Permission from the Lancet Publishing Group , 2022 .

[14]  A. Neumann,et al.  Viral kinetics in patients with chronic hepatitis C treated with standard or peginterferon alpha2a. , 2001, Gastroenterology.

[15]  Alan S. Perelson,et al.  Hepatitis C Viral Dynamics in Vivo and the Antiviral Efficacy of Interferon-α Therapy , 1998 .

[16]  A. Neumann,et al.  Dose‐dependent acute clearance of hepatitis C genotype 1 virus with interferon alfa , 1997, Hepatology.

[17]  N Enomoto,et al.  Mutations in the nonstructural protein 5A gene and response to interferon in patients with chronic hepatitis C virus 1b infection. , 1996, The New England journal of medicine.