GENOTYPE, SLOW DECREASE IN VIRUS TITER DURING INTERFERON TREATMENT AND HIGH-DEGREE OF SEQUENCE VARIABILITY OF HYPERVARIABLE REGION ARE INDICATIVE OF POOR RESPONSE TO INTERFERON TREATMENT IN PATIENTS WITH CHRONIC HEPATITIS TYPE-C

In a study assessing factors associated with a good or a poor response to interferon treatment in patients with chronic hepatitis type C, we analyzed serum samples taken from 26 interferon-treated patients and found further evidence that infection with genotype II is associated w ith a poor response. Whereas all seven patients with group III genotyp e tested showed a good response (normalization of alanine aminotransfe rase level for more than 6 months), only 10 of 19 (53%) patients infec ted with group II genotype showed a good response. We also observed th at 16 of 17 (94%) patients who exhibited a rapid virus titer decrease during the first 2 weeks of treatment later showed a good response. In contrast, only three of nine (33%) patients with an initially slow vi ral decrease eventually showed a good response (p<0.04). None of the 2 6 control patients exhibited a marked virus decrease or normalization of serum alanine aminotransferase level. Interestingly, high degrees o f sequence variability were seen in three patients with group II hepat itis C virus who responded poorly to the therapy. All three showed slo w decreases in virus titer during the first 2 weeks of treatment. In c ontrast, patients with genotype II who showed a good response to treat ment were seen to have very few mutations. In three patients with geno type III who had responded well to interferon treatment, all showed ve ry little amino acid sequence variability in the hypervariable region compared with patients with genotype II who had responded poorly to in terferon treatment. These data suggest that a slow decrease in virus t iter during the beginning of interferon treatment and a high degree of sequence variability, both of which are often seen in patients with g roup II genotype, are associated with poor response to interferon trea tment.