Quasispecies nature of hepatitis C virus and response to alpha interferon: significance as a predictor of direct response to interferon.
OBJECTIVE
We evaluated the significance of the quasispecies nature of HCV as a predictor of the response to alpha interferon therapy in patients with chronic hepatitis C.


METHODS
Natural alpha interferon was administered in 62 patients for 24 weeks (daily for 2 weeks, then three times weekly for 22 weeks) and factors were analyzed that could affect the response. HCV subtype, HCV RNA concentrations and the number of HCV quasispecies were evaluated before treatment. HCV RNA concentrations were measured by branched DNA probe assay. The number of HCV quasispecies was measured by fluorescence single-strand conformation polymorphism analysis.


RESULTS
The HCV RNA concentration (p < 0.0001), HCV subtype (p = 0.0076), and the number of HCV quasispecies (p = 0.0024) were significantly associated with a complete response. Multivariate analyses showed that the number of HCV quasispecies was an independent predictor of the disappearance of HCV RNA during the administration of alpha interferon, but did not predict a relapse after its completion. Pretreatment concentration of HCV RNA was the only factor that was related to a long-term disappearance of HCV RNA.


CONCLUSIONS
The number of HCV quasispecies was significantly related to the response to alpha interferon early in its administration. The pretreatment concentration of HCV RNA was mainly related to a relapse following completion of treatment.
Toyoda
H
H
Department of Gastroenterology, Ogaki Municipal Hospital, Japan.
Kumada
T
T
Nakano
S
S
Takeda
I
I
Sugiyama
K
K
Osada
T
T
Kiriyama
S
S
Sone
Y
Y
Kinoshita
M
M
Hadama
T
T
D000328:Adult; D000367:Age Factors; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D005814:Genes, Viral; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000628:therapy* / Q000821:virology; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D012367:RNA, Viral / Q000032:analysis; D012008:Recurrence; D012737:Sex Factors; D013045:Species Specificity; D016896:Treatment Outcome
D000998:Antiviral Agents; D007135:Immunoglobulin Variable Region; D016898:Interferon-alpha; D012367:RNA, Viral