Predictors of sustained response, relapse and no response in patients with chronic hepatitis C treated with interferon-α


Professor Alfredo Alberti, Clinica Medica 2, via Giustiniani, 2, 35100 Padova, Italy.


Summary. Three main patterns of response are seen when interferon-α (IFN-α) is used for the treatment of chronic hepatitis C:

1 sustained response with alanine-aminotransferase (ALT) normalization that is maintained after cessation of therapy, with or without clearance of serum hepatitis C virus (HCV) RNA;

2 transient response with ALT normalization during therapy followed by relapse after its withdrawal, and

3 no response with no or only partial reduction in ALT levels.

In order to define variables that could predict each of these three types of response we studied 321 cases of chronic hepatitis C treated with IFN-α in two consecutive trials conducted in our Unit. By univariate analysis, age < 45 years (P < 0.01), known disease duration < 60 months (P < 0.01), normal gamma-glutamyltranspeptidase (γGT) levels (P < 0.01) and infection by HCV genotype 2 or HCV genotype 3 (P < 0.01) were found to be statistically associated with sustained response while age > 45 years (P < 0.01), body weight (P= 0.05), cirrhosis (P < 0.01) and elevated γGT levels (P < 0.01) were associated with no response. By multivariate analysis sustained response was predicted by HCV genotype 2 (P < 0.01) and HCV genotype 3 (P < 0.01), known disease duration (P < 0.01), patient's age (P < 0.05) and associated with the use of a more aggressive treatment schedule (P < 0.05). Transient response with relapse was predicted by known duration of disease (P < 0.05), HCV genotype 1 (P < 0.05) and female sex (P < 0.05). No response was statistically associated with elevated γGT levels (P < 0.01), higher body weight (P < 0.05) and with the less aggressive regimen of 3 MU of natural IFN-α given three times weekly for 6 months (P < 0.05).

These results indicate that the HCV genotype as well as the schedule of treatment greatly affect the pattern of response to IFN in chronic hepatitis C and allow us to define criteria to predict which type of response is more likely in individual patients.