Arch Virol (2005) 150: 261–271 DOI 10.1007/s00705-004-0415-7 Genetic variability of hepatitis C virus in HBV/HCV co-infection and HCV single-infection M. S. De Mitri 1 , G. Morsica 2 , R. Cassini 1 , S. Bagaglio 2 , P. Andreone 1 , G. Bianchi 1 , M. Margotti 1 , and M. Bernardi 1 1 Department of Internal Medicine, Cardioangiology and Hepatology, University of Bologna, Bologna, Italy 2 Division of Infectious Disease, Universit` a Vita Salute S. Raffaele Hospital, Milan, Italy Received April 22, 2004; accepted August 16, 2004 Published online October 11, 2004 c  Springer-Verlag 2004 Summary. To describe the virological profile of HCV in HBV/HCV co-infection, we investigated the variability of HVR-1 and NS5A domains, which may be involved in viral persistence and replication efficiency. We studied 95 patients: 37 with serological markers of HBV/HCV co-infection, 33 with single HBV and 25 with single HCV infection. HVR-1 complexity and NS5A gene variability were respectively explored by means of PCR-SSCP and direct sequencing. Serum HBV genomes were detected in all coinfected patients: 19 also had circulating HCV particles (group BC-I), whereas HCV were undetectable in the other 18 (group BC-II). Group BC-I was characterised by a significantly lower HBV replication capacity, that reflects the replicative dominance of HCV, although the dominant virus had the same degree of variability as the HCV in single infection. HBV viral load was higher in group BC-II, but not significantly different from that observed in the single infection. Our data indicate an alternation in replicative dominance in co-infection: HBV can suppress HCV replication to undetectable levels, whereas HCV may reduce but does not abrogate the replication capacity of HBV. Furthermore, in the cases of HCV dominance, circulating HBV genomes did not have a significant effect on the viral heterogeneity of HCV. Introduction Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are responsible for the majority of chronic liver diseases, such as active hepatitis, cirrhosis and hepatocellular carcinoma [17]. In endemic areas, co-infection with both viruses is not uncommon because of their overlapping routes of transmission, although its prevalence may vary from 10% to 15% [8, 33].