Mutations in the nonstructural 5A region of hepatitis C virus and response of chronic hepatitis C to interferon alfa.
OBJECTIVE
Mutations in hepatitis C virus (HCV) nonstructural protein 5A (NS5A) may correlate with response to interferon in Japanese patients with chronic hepatitis C. The aim of this study was to examine whether these findings could be expanded to European patients infected with genotypes associated to low (1b) or high (3a) response rates.


METHODS
Pretreatment serum samples of 66 patients with chronic HCV infection, 48 infected with genotype 1b and 18 with 3a, were analyzed.


RESULTS
Among patients infected with genotype 3a, 1 of 7 long-term responders and none of 11 nonresponders showed NS5A amino acid mutations. Among patients infected with genotype 1b, all 7 long-term responders, but also 27 of 41 nonresponders, showed NS5A mutations. There was no correlation between number of mutations and response to therapy. In 10 patients, sequences obtained before and after treatment were compared and failed to show any change. Serum HCV RNA levels did not differ between patients with and without mutations in NS5A sequence.


CONCLUSIONS
No significant correlation was found in patients infected with genotypes 1b or 3a between NS5A sequence and response to interferon alfa. NS5A mutations do not correlate with viral load. Changes in this region were not found during interferon alfa treatment.
Squadrito
G
G
INSERM Unité 370, Centre hospitalo-universitaire Necker, Paris, France.
Leone
F
F
Sartori
M
M
Nalpas
B
B
Berthelot
P
P
Raimondo
G
G
Pol
S
S
Bréchot
C
C
D000328:Adult; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000627:therapeutic use*; D001483:Base Sequence; D002908:Chronic Disease; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D006526:Hepatitis C / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis / Q000097:blood / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism
D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins