| |
Can You Have Multiple Genotypes?
|
| |
| |
"Changes in the Prevalence of Hepatitis C Virus Genotype among Injection Drug Users: A Highly Dynamic Process"
The Journal of Infectious Diseases 2004;190:1199-1200
Matthias Schröter, Bernhard Zöllner, Rainer Laufs, and Heinz-Hubert Feucht
Zentrum für Klinisch-Theoretische Medizin I, Institut für Infektionsmedizin, Universitätsklinikum Hamburg Eppendorf, Hamburg, Germany
To the Editor—With great interest we have read the article by van Asten et al. in The Journal of Infectious Diseases [1]. An important aspect of their study is its detailing of the introduction and spread of "new" hepatitis C virus (HCV) genotypes among injection drug users (IDUs).
Changes of subtype distributions in a given population were shown, for the first time, by our group several years ago [2]. In that study, it was demonstrated that subtype 1b was the prevailing subtype in the German population until subtype 1a started spreading in the early 1980s [2]. This led to a substantial change of the most prevalent HCV subtype, especially in younger people. To highlight the question of whether this change was a single effect, a multicenter study was performed 2 years ago [3]. In that study, we demonstrated that the epidemiology of HCV genotypes in IDUs is subjected to highly dynamic changes. Profound changes in the prevalence of different HCV genotypes were noted between 1994--1995 and 2000--2001, when large populations of IDUs (n = 144 and n = 172, respectively) were compared. These changes are summarized in figure 1. The introduction of genotypes that were formerly unknown in this risk population (4 and 2a/b) and the ability of these genotypes to establish significant prevalence within a period of only 6 years are remarkable.
The theory of 2 independently developing HCV epidemics had been proposed elsewhere [4], because the epidemiology of HCV subtype 3a and other subtypes seemed to be very different between IDUs and non-IDUs. However, there are indications that the dynamics observed among IDUs also influence the genotypic distribution among the entire population of patients. Although subtype 3a was detected nearly exclusively among IDUs in 1994--1995, 〜45% of patients infected with subtype 3a had never been IDUs. In the majority of these people, high-risk sexual behavior (HRSB) was the most probable risk factor for acquiring HCV infection [3]. It can be assumed from these data that the higher the prevalence of a certain genotype among the population of IDUs, the higher is the risk of this genotype spreading beyond the boundaries of the IDU scene. This is most probably due to HRSB, which, today, is one of the major risk factors for acquiring HCV [3, 5]. On the other hand, new genotypes can be introduced in the population of IDUs. This has been demonstrated very convincingly for genotype 4, which was introduced by immigrants from northern Africa and the Arabian peninsula [1, 3], and for genotype 2 [3]. In our population of patients, these genotypes established a prevalence of 7% and 8%, respectively, within only 6 years (figure 1). In analogy to the findings for subtype 3a, these genotypes may also spread over the boundaries of the IDU scene with increasing prevalence.
However, knowledge of these dynamic changes of the distribution of HCV genotypes provides information regarding not only the epidemiology, but also the treatment, of HCV. In a population with a high risk of repeated HCV infections, the probability of infection with different HCV genotypes is associated with the speed of changes of the genotype distribution. We have shown that, in at least 18% of IDUs with long-term follow-up (up to 7 years), multiple HCV infections detected by intraindividual changes of the predominant HCV genotype occurred [6].
It is well known that, in patients infected with multiple HCV genotypes, one of the infecting virus strains establishes predominance, and, by use of polymerase chain reaction--based methods, usually only the actual prevailing strain can be detected in these patients [7]. However, minor strains do not become eliminated, and we have demonstrated in various patients that these minor strains can reappear [6, 8]. These findings are of importance, especially in the context of therapy with pegylated interferon and ribavirin. It has been shown that reemergence of minor strains is a possible cause for failure of therapy [6, 8]. Therefore, the recommendation was made to repeat genotyping in patients who do not respond to therapy as expected. This enables adjustment of the regimen to the actual predominant HCV genotype.
These findings underline the importance of the described dynamic changes of the epidemiological distribution of HCV genotypes among IDUs They are important for better understanding (1) the epidemiology of HCV and (2) possible factors influencing outcome of therapy.
References
1. van Asten L, Verhaest I, Hernandez-Aguado I, et al. Spread of hepatitis C virus among European injection drug users infected with HIV: a phylogenetic analysis. J Infect Dis 2004; 189:292--302.
2. Feucht HH, Schröter M, Zöllner B, Polywka S, Nolte H, Laufs R. The influence of age on the prevalence of hepatitis C virus subtypes 1a and 1b. J Infect Dis 1997; 175:685--8.
3. Schröter M, Zöllner B, Schäfer P, et al. Epidemiological dynamics of hepatitis C virus among 747 German individuals: new subtypes on the advance. J Clin Microbiol 2002; 40:1866--8.
4. Pawlotsky JM, Tsakiris L, Roudot-Thorval F, et al. Relationship between hepatitis C virus genotypes and sources of infection in patients with chronic hepatitis C. J Infect Dis 1995; 171:1607--10.
5. Alter MJ, Kruszon-Moran D, Nainan OV, et al. Prevalence of hepatitis C virus infection in the United States. N Engl J Med 1999; 341:556--62.
6. Schröter M, Zöllner B, Schäfer P, Laufs R, Feucht HH. The rapidly changing epidemiology of HCV genotypes: consequences for the individual therapeutic regimen [session WD4]. In: Program and abstracts of the 11th International Symposium on Viral Hepatitis and Liver Disease (Sydney). Adelaide: Australian Centre for Hepatitis Virology, 2003:95.
7. Widell A, Mansson S, Persson NH, Thysell H, Hermodsson S, Blohme I. Hepatitis C superinfection in hepatitis C virus (HCV)--infected patients transplanted with an HCV-infected kidney. Transplantation 1995; 60:642--7.
8. Schröter M, Feucht HH, Zöllner B, Schäfer P, Laufs R. Multiple infections with different HCV genotypes: prevalence and clinical impact. J Clin Virol 2003; 27:200--4.
J Clin Virol. 2003 Jul;27(2):200-4.
Multiple infections with different HCV genotypes: prevalence and clinical impact.
Schroter M, Feucht HH, Zollner B, Schafer P, Laufs R.
Institut fur Medizinische Mikrobiologie und Immunologie, Universitatsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany. mschroet@uke.uni-hamburg.de
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.
|
|
| |
| |
|
|
|
