PRETREATMENT VIRUS LOAD AND MULTIPLE AMINO-ACID SUBSTITUTIONS IN THE INTERFERON SENSITIVITY-DETERMINING REGION PREDICT THE OUTCOME OF INTERFERON TREATMENT IN PATIENTS WITH CHRONIC GENOTYPE 1B HEPATITIS-C VIRUS-INFECTION
K. Chayama et al., PRETREATMENT VIRUS LOAD AND MULTIPLE AMINO-ACID SUBSTITUTIONS IN THE INTERFERON SENSITIVITY-DETERMINING REGION PREDICT THE OUTCOME OF INTERFERON TREATMENT IN PATIENTS WITH CHRONIC GENOTYPE 1B HEPATITIS-C VIRUS-INFECTION, Hepatology, 25(3), 1997, pp. 745-749
Hepatitis C virus (HCV) genotype Ib and high pretreatment virus load a
re predictive factors of poor response to interferon therapy in patien
ts with chronic hepatitis C. To further examine the factors predicting
the response to interferon in patients with genotype Ib infection, we
analyzed 110 consecutive patients with HCV who were treated with a to
tal of 624 million units of lymphoblastoid interferon alfa. Thirty-six
patients (33%) were responders, while the remaining 74 patients (67%)
were nonresponders. Multivariate analysis showed that a high virus ti
ter (assessed by serum core protein level, P = .0021) and the presence
of more than two amino acid substitutions in the interferon sensitivi
ty-determining region (ISDR) (P = .0036) correlated significantly with
the response to interferon therapy. Because mutations analyzed by dir
ect sequencing of polymerase chain reaction (PCR) products may reflect
artifacts of direct sequencing, we further analyzed quasispecies of H
CV in this region by cloning and sequencing. Although PCR-based analys
is of responders with multiple amino acid substitutions in the ISDR sh
owed the presence of a small amount of wild-type strain in their serum
, the results obtained by direct sequencing and cloning were essential
ly the same. A longitudinal study of quasispecies in 2 patients who sh
owed a dramatic change in the virus titer showed no conversion from wi
ld type to mutant or vice versa. Our results indicate that amino acid
substitutions and virus load are independent predictors of the respons
e to interferon therapy. The ability of some patients with no mutation
in the ISDR or high virus load to eliminate the virus suggests the pr
esence of other unidentified factors, host or viral, that influence th
e response to interferon therapy.