Journal of Clinical Virology 31 (2004) 253–258 HCV genotype 4—an emerging threat as a cause of chronic liver disease in Indian (south) patients Sukanya Raghuraman a , Priya Abraham a,∗ , Gopalan Sridharan a , Hubert Darius Daniel a , B.S. Ramakrishna b , R.V. Shaji c a Departments of Clinical Virology, Christian Medical College, Vellore 632004, Tamil Nadu, India b Departments of Gastrointestinal Sciences, Christian Medical College, Vellore 632004, Tamil Nadu, India c Departments of Haematology, Christian Medical College, Vellore 632004, Tamil Nadu, India Received in revised form 22 March 2004; accepted 31 March 2004 Abstract Background: Hepatitis C virus (HCV) genotyping is relevant for the delivery of effective antiviral therapy. HCV genotypes are geographically restricted with genotype 4, which is resistant to therapy, traditionally considered to be confined to the Middle East and Africa. We report here on the occurrence of HCV genotype 4 in Indian (South) patients. Objectives: (1) To highlight the occurrence of HCV genotype 4 in the patient population attending a tertiary care hospital in south India. (2) To ascertain the difference in HCV viral loads and alanine aminotransferase (ALT) values between patients infected with HCV genotype 4 and those infected with the other two most commonly detected genotypes in this patient population viz., HCV genotypes 1 and 3. (3) To assess the genetic relatedness of the Indian strains to Genbank sequences, which we report for the first time. Study design: The study group consisted of 125 HCV infected, untreated patients who had been genotyped using type specific primers. Eight of the nine samples classified as HCV genotype 4 by this technique were subjected to nucleotide sequencing. Viral load estima- tions were carried out. Information on possible risk factors and ALT values were obtained from hospital records. Statistical analyses were carried out to compare viral loads and ALT values across genotypes. A phylogenetic tree was constructed and the genetic relatedness of the strains was assessed through sequence analysis. Results: HCV genotype 4 was detected in nine of 125 (7.2%) patients. Eight of the nine were subjected to nucleotide sequencing and all strains were confirmed as HCV genotype 4. Six of the eight strains were closely re- lated, with two strains being phylogenetically diverse. Conclusions: HCV genotype 4 is detected in a significant minority of HCV infected patients in India. This finding should be considered in designing strategies prior to initiation of therapy in Indian patients infected with HCV. © 2004 Elsevier B.V. All rights reserved. Keywords: Hepatitis C virus; Genotype 4; India; Phylogenetic analysis 1. Introduction The heterogeneity of the hepatitis C virus (HCV) genome has warranted the classification of the virus into different genotypes. It is now well established that there are a num- ber of different genotypes of HCV (Simmonds et al., 1993), which may have important implications in the pathogenesis ∗ Corresponding author. Tel.: +91 416 2282616/2282772; fax: +91 416 2232035. E-mail address: priyaabraham@cmcvellore.ac.in (P. Abraham). of disease (Pozzato et al., 1994), response to anti-viral ther- apy (Hopf et al., 1996), diagnosis (Neville et al., 1997), in molecular epidemiology studies and vaccine development. Genotypes of HCV are thought to be geographically re- stricted with the exception of genotype 1. HCV genotype 1 and its subtypes are distributed throughout the world. Geno- type 2 is mainly found in Europe and type 3 in Europe and Asia. Reports of genotype 4 have mainly emanated from Egypt (Ray et al., 2000), Saudi Arabia, (Shobokshi et al., 1998), Italy (Argentini et al., 2000) and France (Morice et al., 2001). Genotype 5a has been isolated from blood donors 1386-6532/$ – see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.jcv.2004.03.019