Molecular and epidemiological profiles of hepatitis C virus genotype 4 in Denmark

Abstract

The prevalence of hepatitis C virus (HCV) genotype 4 has increased throughout Europe. This is an epidemiological study of patients infected chronically with HCV genotype 4 in Denmark. The HCV strains analyzed originated from patient samples collected between 1999 and 2007 as part of the national Danish hepatitis B and C network, DANHEP. Sequence analyses were based on the envelope 1 region of HCV. Results from a total of 72 patients indicated a high degree of genetic heterogeneity. Fifty‐six patients (78%) were infected with one of the three dominating subtypes: 4d, 4a, or 4r. The remaining 16 patients (22%) were infected with subtypes 4h, 4k, 4l, 4n, 4o, or 4Unclassified. Three epidemiological profiles were identified: (1) patients infected with HCV by intravenous drug use were infected solely with subtype 4d. They were all of European origin, and 15 of the 16 patients were ethnic Danes. No single transmission event could be confirmed, but the pairwise nucleotide identity within the patients of Danish origin was relatively high (∼95%), suggesting a recent introduction into Denmark. (2) The 21 patients infected with subtype 4a all came from Northern Africa, Egypt, Pakistan, or the Middle East. (3) Patients from Southern Africa dominated among patients infected with subtype 4r (10 of 12 patients). This study demonstrates that HCV genotype 4d has been introduced in and spread among Danish intravenous drug users. The remaining subtypes show restricted distribution, infecting almost exclusively patients from geographical areas with a relatively high prevalence of HCV genotype 4 infections. J. Med. Virol. 82:1869–1877, 2010. © 2010 Wiley‐Liss, Inc.

The epidemic dynamics of hepatitis C virus subtypes 4a and 4d in Saudi Arabia

“…Our results show that recent HCV4a transmissions between countries likely have an origin in Egypt (Table 2), which is in line with previous findings concerning a central role of this country in the global HCV4a epidemic272829. Virus spread between Saudi Arabia and Egypt is predominantly directed towards Saudi Arabia, showing that both HCV4a epidemics are connected through a source-sink relation, perhaps linked to the large flow of Egyptian migrant workers13.…”

Hepatitis C Virus Infection Epidemiology among People Who Inject Drugs in Europe: A Systematic Review of Data for Scaling Up Treatment and Prevention

“…Genotype 4 has been spreading in Western Europe since the 1960s [217]. It appears to be genetically diversifying and increasing in particular among PWID in Europe [46], [113], [128], [137], [140], [144], [218]–[220]. Countries with predominance of genotypes 1 and high or increasing levels of genotype 4 face more difficulties in treating PWID with peginterferon and ribavirin.…”

Near‐full genome characterization of unclassified hepatitis c virus strains relating to genotypes 1 and 4

“…The genetic variation between these subtypes and the strains found in this study (17-19%) is smaller than the criteria for subtype discrimination [Simmonds et al, 2005], but they belong to distinct subtypes, representing the epidemiological associations of these variants and indicating possibly a continual genetic variation of HCV with many variants still missing [de Bruijne et al, 2009;Li et al, 2009]. Epidemiologically distinct infections of this variant have been found in patients of African origin in Canada, Britain, and Denmark [Murphy et al, 2007;Demetriou et al, 2009;Eriksen et al, 2010], and in this study two near-full genome reference sequences of this novel type are presented for the first time. Therefore, based on the results of the sequence analysis, the genetic variations from other subtypes, and the current picture of subtype classification in HCV genotype 4, it is proposed that this group of strains should be designated as subtype 4v.…”