Molecular characterisation of HCV genotype 4 isolates circulating in Italy.

The characteristics of genotype 4 subtype variability of HCV isolates circulating in Italy were studied. The viral isolates were identified from 736 HCV-RNA positive sera originated from seroepidemiological studies undertaken in 4 different regions of North, South Italy and Sardinia. 24 out of 28 genotype 4 isolates (86%) were classified by phylogenetic analysis of E1 genome region (915-1128) as belonging to subtype 4d (Neighbour Joining Method). Three isolates classified as subtype 4a were detected in haemophilic patients, possibly related to infections from blood products. One isolate classified as a new subtype derived from an Eritrean patient subjected to haemodialysis. Very high genome homogeneity (mean 4.3%) was shown by genetic comparisons (DNA dist programs Phylip Package) for all the 4d isolates relative to the studies performed in Veneto, Calabria and Sardinia and originated from subjects from the general population and outpatients (19 subtype 4d isolates out of 24). In the 3 studies different prevalence rates of HCV genotype 4 (3.1%, 1. 3%, 14% respectively) were found. In contrast a considerable degree of heterogeneity, both intragroup and with the other groups (mean 8. 2% and 8.7%, respectively) was observed among subtype 4d isolates identified in the patients of a haemodialysis centre in Apulia region. In conclusion the subtype 4d of genotype 4 was highly prevalent and endemic in Italy. An elevated level of viral heterogeneity was observed in one study carried out in a region of Southern Italy. This can be related to a longer period of past endemicity of this genotype and to a high level of exposure to reinfections in particular categories of patients such as haemodialysis patients.