Objective: To analyze the distribution of hepatitis C virus (HCV) geno
types among patients positive for antibody to HCV (anti-HCV) according
to age, severity of liver disease, and duration of infection; to inve
stigate the influence of HCV genotypes on response to interferon-alpha
therapy; and to study HCV viremia levels in relation to genotypes and
severity of liver disease. Design: Cross-sectional study. Setting: 3
university hospitals and 2 research units. Patients: 3 groups of Frenc
h and Italian patients with chronic HCV infection and detectable serum
HCV RNA: Group 1 included 35 patients with hepatocellular carcinoma;
group 2, 71 patients with cirrhosis who did not have hepatocellular ca
rcinoma; and group 3, 114 patients with chronic active hepatitis. 106
of the patients with chronic hepatitis or cirrhosis were treated with
interferon-alpha (3 MU subcutaneously 3 times/wk for greater than or e
qual to 6 months). Measurements: Genotyping by polymerase chain reacti
on with capsid-specific primers; serum HCV RNA by branched DNA (bDNA)
signal amplification. Results: Hepatitis C virus genotype 1b (II) was
the most prevalent genotype (61.8%). In a univariate analysis, it was
associated with older age (<40 years, 47.4%; greater than or equal to
60 years, 80.4%; P = 0.001), longer duration of disease (less than or
equal to 10 years, 40.4%; greater than or equal to 20 years, 86.7%; P
= 0.005), and cirrhosis with or without hepatocellular carcinoma 78.4%
compared with 53.8% for chronic hepatitis; P < 0.001). Viremia levels
did not differ between patients infected with HCV type 1b (II) and th
ose infected with other HCV genotypes. Patients with HCV type 1b (II)
responded to interferon-alpha therapy significantly less than did pati
ents with other HCV genotypes (P = 0.01). In a multivariate analysis,
age and cirrhosis were independently associated with HCV genotype 1b (
II). Genotype and HCV viremia level were independent predictors of res
ponse to interferon-alpha therapy. Conclusions: The prevalence of HCV
genotypes in French and Italian patients has been changing; the preval
ence of HCV type 1b (II) infection has progressively decreased, althou
gh it still accounts for most HCV-related cirrhosis and hepatocellular
carcinoma. High HCV viremia levels and HCV genotype type 1b (II) are
independent predictors for poor response to interferon-alpha therapy a
nd should be considered in the management of patients with HCV infecti
on.