Multiple infections with different HCV genotypes: prevalence and clinical impact
Introduction
The genotype of hepatitis C virus (HCV) has been described as an independent predictor of success of antiviral therapy (Zeuzem et al., 2000). Therefore, different therapy regimens have been proposed depending on the infecting HCV genotype (Zeuzem et al., 2000). Before onset of therapy the actual viremic HCV strain is usually determined by a PCR-based method like nucleotide sequencing. However, it is well known from transplant patients that superinfection with a new HCV strain leads to suppression of one virus under the detection limit of PCR while the other one prevails as the viremic strain (Widell et al., 1995).
Repeated exposure to HCV is also common in high-risk groups like inravenous drug users (IVDU) or patients on maintenance hemodialysis (Alter et al., 1999). This study was initiated because only limited data are available about the epidemiology and about therapeutical consequences of superinfection with a new HCV strain.
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Serum samples
Sera were drawn from 600 unselected HCV PCR-positive individuals which were sent to our laboratory between July and December 2001. HCV viremia was proven by PCR as previously described (Schröter et al., 2001a). None of the patients was treated with α-interferon at the time of investigation. All of them gave informed consent to participate in this study.
Nucleotide sequencing of a part of the 5′ non-coding region:
Sequencing of a part of the 5′ non-coding region was performed as previously described (Schröter et al., 2001b). Briefly, RNA was extracted
Results
A cross-sectional study was performed comprising 600 unselected HCV PCR-positive serum samples. HCV genotyping was determined in parallel by the antibody assay and by nucleotide sequencing. Discordant results in both assays occurred in 13 samples (2.2%) (Table 1).
Twelve of those (92.3%) were initially infected by a subtype of genotype 1 as detected by NS-4 IBA. Nine were determined as subtype 1a, three were subtype 1b, and in only one sample a 3a strain was detected initially. However, the
Discussion
The driving force for the initiation of this study was the case of a chronically hepatitis C virus (HCV)- infected patient who failed to respond as expected to antiviral therapy with pegylated interferon-alfa (peg-IFN-α) and Ribavirin. Prior to therapy HCV subtype 3a, which is known for its favourable therapy outcome (response rate>70%) (Zeuzem et al., 2000), was determined on two occasions by nucleotide sequencing of the viral 5′-untranslated region as described earlier (Schröter et al., 2001b
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