Viral decline over 48h and HCV amino acid mutations are related to efficacy of PEG-IFN/ribavirin.
OBJECTIVE
The relationship between mutations and HCV dynamics has not been fully studied in terms of the efficacy of PEG-IFN/Rib combination treatment. Here we aimed to systematically examine HCV dynamics during PEG-IFN/Rib treatment and evaluate the association between amino acid (aa) substitutions in HCV and efficacy of PEG-IFN/Rib treatment.


METHODS
Patients (n=36) having HCV genotype 1b infection and high viral loads with PEG-IFN/Rib for 48 weeks were treated. HCV RNA levels were quantified every 24h from 0-144h after initial injection of PEGIFN and every month thereafter. The aa substitutions in HCV core region (CoreR) and interferon sensitivity determining region (ISDR) were determined at baseline. On the basis of treatment response, we divided patients into 3 groups: sustained virological response (SVR: n=18), transient response (TR: n=9) and no response (NR: n=9).


RESULTS
Patients with double wild type (DW) in CoreR had higher SVR rate as compared to patients with non-double wild type (NDW) in CoreR (58% vs. 33%). Patients with =2 aa substitutions in ISDR had significantly higher SVR rate compared with patients with =1 aa substitution in ISDR (71% vs. 36%). Further, 68% patients who exhibited =2-log decline in HCV-RNA levels within the initial 48h of treatment achieved SVR, and only 18% patients who reached <2 log declines did not achieve SVR. Patients who reached =2 log declines in HCV-RNA levels within the initial 48h of treatment with DW in CoreR or =2 aa substitutions in ISDR could achieve SVR and those with NDW in CoreR or =1 aa substitution in ISDR could not achieve SVR.


CONCLUSIONS
The combination of the apparent =2-log decline in HCV RNA level within the initial 48h and aa substitutions in CoreR and ISDR may be useful predictors of PEG-IFN/Rib treatment.
Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan. akimiya@iwate-med.ac.jp
Akio
A
Miyasaka
Ichiro
I
Kumagai
Koichi
K
Abe
Kazuyuki
K
Suzuki
D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D007564:Japan; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018579:Patient Selection; D010641:Phenotype; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D012254:Ribavirin / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects*; D055815:Young Adult
D000998:Antiviral Agents; D015415:Biomarkers; D012367:RNA, Viral; D011092:Polyethylene Glycols; D012254:Ribavirin; D007372:Interferons