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 < or = 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 > or = 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 > or = 6 and IRRDR < or = 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 (> or = 6 mutations in the IRRDR) and 7.7% (1/13) in the RI-C group (< or = 5 IRRDR mutations) (p = 0.0003).
Sasase
Noriko
N
Department of Pharmacy, Kobe Asahi Hospital, Kobe, Japan.
Kim
Soo Ryang
SR
Kudo
Masatoshi
M
Kim
Ke Ih
KI
Taniguchi
Miyuki
M
Imoto
Susumu
S
Mita
Keiji
K
Hayashi
Yoshitake
Y
Shoji
Ikuo
I
El-Shamy
Ahmed
A
Hotta
Hak
H
D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D044967:Serum / Q000821:virology; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b