TABLE 1.
Patient | Sex | Age (yr) | Liver histologya | Response to IFN-αb | Viral load (log10 copies/ml)c | Nd | Normalized entropy
|
Mean genetic distance (SEM) within samplese | Type of mutational changef
|
||
---|---|---|---|---|---|---|---|---|---|---|---|
Nucleo- tide | Amino acid | Mean (SEM) synonymous | Mean (SEM) nonsynonymous | ||||||||
1 | Female | 37 | CAH | SVR | 5.5 | 30 | 0.156 | 0.114 | 0.0715 (0.0279) | 0.2022 (0.0668) | 0.0373 (0.0143)* |
2 | Male | 32 | CAH | SVR | 5.9 | 31 | 0.265 | 0.246 | 0.0135 (0.0017) | 0.0000 (0.0000) | 0.0183 (0.0084) |
3 | Male | 53 | CAH | SVR | 3.9 | 48 | 0.127 | 0.085 | 0.0115 (0.0012) | 0.0101 (0.0102) | 0.0116 (0.0069) |
4 | Male | 30 | CAH | SVR | 4.2 | 48 | 0.219 | 0.000 | 0.0110 (0.0012) | 0.0362 (0.0216) | 0.0032 (0.0032) |
5 | Female | 38 | CAH | SVR | 4.7 | 36 | 0.455 | 0.436 | 0.0608 (0.0107) | 0.1220 (0.0401) | 0.0287 (0.0103)* |
6 | Male | 44 | CAH | NR | 5.3 | 30 | 0.236 | 0.180 | 0.0391 (0.0109) | 0.1279 (0.0539) | 0.0131 (0.0093)* |
7 | Female | 69 | CAH | NR | 5.4 | 30 | 0.695 | 0.466 | 0.0656 (0.0039) | 0.2007 (0.0562) | 0.0264 (0.0090)** |
8 | Male | 32 | CAH | NR | 6.2 | 35 | 0.439 | 0.085 | 0.0380 (0.0061) | 0.1340 (0.0444) | 0.0112 (0.0056)** |
9 | Male | 55 | CAH | NR | 5.6 | 40 | 0.424 | 0.240 | 0.0262 (0.0028) | 0.0846 (0.0295) | 0.0090 (0.0054)* |
10 | Male | 67 | CAH +cirrhosis | NR | 5.8 | 36 | 0.761 | 0.473 | 0.0643 (0.0021) | 0.2135 (0.0508) | 0.0239 (0.0088)*** |
11 | Female | 63 | CAH | NR | 5.7 | 34 | 0.750 | 0.331 | 0.0528 (0.0032) | 0.2053 (0.0590) | 0.0131 (0.0067)** |
12 | Male | 28 | CAH | NR | 5.6 | 48 | 0.652 | 0.226 | 0.0371 (0.0023) | 0.1158 (0.0378) | 0.0116 (0.0070)** |
13 | Female | 64 | CAH | NR | 6.1 | 36 | 0.551 | 0.291 | 0.0595 (0.0047) | 0.2073 (0.0532) | 0.0200 (0.0076)**** |
CAH, chronic active hepatitis.
SVR, sustained virological response, characterized by normal ALT and negative HCV RNA PCR during treatment and 6 months after; NR, nonresponse, characterized by the lack of effect of IFN-α on ALT and HCV RNA.
Viral load was measured by the Amplicor HCV Monitor assay (Roche Molecular Systems, Branchburg, N.J.).
Number of independent clones analyzed before treatment.
The within- and between-sample genetic distances within NS5A quasispecies were calculated by using the DNADIST program in the PHYLIP package version 3.752 (20).
The proportions of synonymous mutations per synonymous site and of nonsynonymous mutations per nonsynonymous site were calculated by means of the MEGA program (39). P values lower than 0.05 were considered to indicate significant differences. The proportion of synonymous substitutions per potential synonymous site was compared to the proportion of nonsynonymous mutations per potential nonsynonymous site by using a t test (*, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001; P ≥ 0.05 was considered not significant).