Prevalence and Changes in Hepatitis C Virus Genotypes among Multitransfused Persons with Hemophilia

Abstract

The purpose of this study was to determine hepatitis C virus (HCV) genotypes and their relationship to HCV RNA levels over time in a cohort of multitransfused hemophiliacs. Following reverse transcription and polymerase chain reaction amplification of HCV RNA, the product DNAs were genotyped by using the line probe assay. HCV RNA was quantified by the branched-chain DNA assay. Genotyping was done on 109 serum samples from 32 subjects. Genotype 3a had the highest prevalence (41%), followed by genotypes 1a (31%) and 1b (13%). Changes in genotypes were observed in 18 (58%) of the subjects >3-15 years of age. Changes were more common in human immunodeficiency virus (HIV)-positive subjects (13/17) than in HIV-negative subjects (5/15) (P=.014). HCV RNA increased 30-fold in HIV-positive subjects whose genotypes changed. Consensus nucleotide sequencing confirmed genotype changes in 2 patients. We conclude that genotype changes are common in hemophiliacs with chronic HCV, particularly in those who are coinfected with HIV.

Mixed Genotypes in Hepatitis C Virus Infection

“…Some groups investigated the dynamics of the change in genotype in more detail, analyzing series of samples from different time points. There was no obvious trend towards replacement with any particular variant Eyster et al, 1999). Regardless the origin of the genotype shift (reinfection or reactivation), it could be revealing the presence of a mixed infection in the hemophilic patient.…”

“…However, selective transmission of HCV isolates during experimental chimpanzee infections and among humans exposed to commercially prepared factor VIII concentrate (lot DO56) containing multiple HCV species has also been suggested (Nainan et al, 2006). The analysis of genotype distribution showed that several HCV genotypes might be circulating simultaneously in adults with hemophilia who received clotting factor concentrates before 1985 Eyster et al, 1999;Schröter et al, 2003). Genotyping studies of multitransfused haemophiliacs suggested that the frequency of HCV mixed infection is high in this group but dissimilar rates of mixed infections were reported by different groups (Table 1).…”

“…When individuals are infected with more than one genotype, changes in the predominant genotype over time could be observed. As a result of immunologic pressure, genetic interaction between virus and host, or treatment intervention, the establishment of the dominant genotype may change over time Eyster et al, 1999;Schröter et al, 2003). Genotype changes were noted more frequently in the HIV-positive subjects than in the HIVnegative subjects.…”

“…Genotype changes were noted more frequently in the HIV-positive subjects than in the HIVnegative subjects. Some reports provided evidence of association between HIV status and the likelihood of HCV genotype to change, possibly related to loss of immune function and a consequent greater susceptibility to the new predominant viral variant Eyster et al, 1999). In the hemophilic population, changes in HCV genotype could be due to reactivation or reinfection but depending on which period is being evaluated is more likely to find one or the other.…”

Hepatitis C virus quasispecies in HIV-infected women: Role of injecting drug use and highly active antiretroviral therapy (HAART)

“…63 Nevertheless, chronically infected humans remain susceptible to new infection. Eyster et al 64 documented a common change of infecting HCV genotypes over time in high-risk patients with hemophilia and recently Herring et al 65 identified superinfection in 20% of active IDUs over a period of 12 months. Similarly, it was shown that chronically infected patients can be superinfected with new HCV strains in the setting of blood transfusion, where HCV-positive patients were exposed to HCV-positive blood, 66 and in the setting of liver transplantation, where patients with HCV-related liver disease receive organs from HCV-infected donors.…”