Multiple infections with different HCV genotypes: prevalence and clinical impact

doi:10.1016/S1386-6532(02)00264-0

Journal of Clinical Virology

Volume 27, Issue 2, July 2003, Pages 200-204

https://doi.org/10.1016/S1386-6532(02)00264-0 Get rights and content

Abstract

Background: In a HCV genotype 3a-infected patient, viremia with a different genotype (1b) was detected after 16 weeks of ineffective therapy. Serological typing revealed that this genotype had already been present prior to therapy. Objectives: To investigate the epidemiology of multiple HCV infections and the therapeutical consequences for patients superinfected with a new HCV strain. Methods: Sera of 600 patients were screened for infection with multiple genotypes by using sequencing and a serological assay in parallel. Results: Infection with two different HCV types was detected in 13 patients. The prevailing strain was genotyped by sequencing. From two of these patients additional sera were available which had been drawn up to 24 and 28 months prior to the current sample, respectively. Those early samples showed viremia with a HCV subtype that could not be detected by PCR afterwards. Only antibodies to the initial strain were detectable in the later samples. Conclusion: In patients serially infected by different HCV strains, one strain will prevail as the viremic virus. Under antiviral therapy, the displaced strain may become viremic again and may influence the outcome of therapy. Detection of inferior strains by serological assays before antiviral therapy may be important for choosing the adequate regimen.

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.

Section snippets

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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Multiple infections with different HCV genotypes: prevalence and clinical impact

Abstract

Introduction

Section snippets

Serum samples

Nucleotide sequencing of a part of the 5′ non-coding region:

Results

Discussion

Lancet

J. Clin. Virol.

Prevalence of hepatitis C virus infection in the United States, 1988 through 1994

N. Engl. J. Med.

Genetic organization and diversity of hepatitis C virus

Proc. Natl. Acad. Sci. USA

Two successive hepatitis C virus infections in an intravenous drug user

J. Clin. Microbiol.

Antibodies of symptomatic human immunodeficiency virus type 1-infected individuals are directed to the V3 domain of noninfectiuos and not of infectious virions present in autologous serum

J. Virol.