16 More recently, typing is often performed by direct sequencing, INNO-LiPA assay,19 Abbot RealTime HCV Genotype II assay20 or hybridization of type-specific probe to PCR amplified 5′ untranslated region DNA fragments.21 Okamoto et al., who determined the nucleotide sequence of genotype 2,17 identified other major genotypes from patients in Vietnam.22 These were later re-classified into genotypes 4, 5 and 6 by Simmonds et al.23 using a new nomenclature system based on maximum likelihood phylogenetic analysis of full-length coding sequences. The classification has been further updated and consensus proposals for genotype and subtype nomenclature have been noted.24 Recently, identification of

a seventh genotype was reported from patients in central Africa.25 There are now more than 200 full HCV genome sequences in the DDBJ/EMBL/GenBank database. Fig. 3 shows a phylogenetic tree based on full-length nucleotide sequences containing Adriamycin concentration the newly described genotype 7a.25 It is now possible to compare the prevalence of each genotype and retrieve data from the

Hepatitis C Virus database at Los Alamos (United States).26 Two other databases, the Hepatitis Virus Database (Japan)27 and euHCVdb (France),28 also provide valuable HCV genotype information. BGJ398 cost No apparent differences between the pathobiology of HCV genotypes was reported until Mihm et al.29 identified a relationship between hepatic steatosis and HCV genotype 3 infection. Subsequent studies confirmed the relationship between steatosis and HCV genotype 3 infection by comparing patients infected with genotype 3 and those infected with other genotypes,30–34 with regard to genotype 3 viral load,35 or by observing improvement of steatosis after elimination the virus with interferon.36–38 The specific amino acid sequences in the core protein that are related to steatosis in genotype 3 HCV infected patients have been identified, although these results should be further confirmed.39,40 A study in which genotype 3 core protein was

introduced Arachidonate 15-lipoxygenase using adenovirus vector provided experimental evidence of the effect of core protein expression on steatosis in hepatocytes.41 Of note, the relationship between different levels of hepatic steatosis in patients infected with genotype 3 and host genetic single nucleotide polymorphisms (SNP) was identified,42 suggesting that a small difference in host genetic factors may result in different outcomes of the disease with the same pathogen. Epidemiological and clinical aspects of the relationship between HCV and steatosis is reviewed by Hwang et al.43 in this issue of JGH. The most important clinical property of HCV genotype is different susceptibility to interferon (IFN) therapy among genotypes. We and others have reported that genotype 1b is the most prevalent genotype in Japan and the most resistant to IFN therapy.