INFO: Genotype

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Genotype

What does the term genotype mean?Genotype refers to the genetic make-up of an organism or a virus. There are at least six distinct HCV genotypes identified. Genotype 1 is the most common genotype seen in the U.S. HCV is an RNA virus related to the flavivirus family. RNA viruses are genetically less stable than DNA viruses and are prone to mutate during replication. It’s a common misconception that hepatitis C is just one virus, but in reality (as a result of mutation over hundreds of years), it’s a group of very closely related strains. They are similar enough to be called HCV, but based on genetic differences, they can be classified into distinct groups called genotypes.

Is it necessary to do genotyping when managing a person with chronic hepatitis C? No. Although persons with genotype 1 respond less often to treatment, genotype should not be a deciding factor on whether or not to treat. With newer therapies, however, treatment regimens might differ on the basis of genotypes.

Why do most persons remain infected?Persons infected with HCV mount an antibody response to parts of the virus, but changes in the virus during infection result in changes that are not recognized by preexisting antibodies. This appears to be how the virus establishes and maintains long-lasting infection.

Can persons become infected with different genotypes?Yes. Because of the ineffective immune response described above, prior infection does not protect against reinfection with the same or different genotypes of the virus. For the same reason, there is no effective pre- or postexposure prophylaxis (i.e, immune globulin) available.

What is a Quasispecies?As the virus continues to replicate in each person, there is the potential for quasispecies to form. Quasispecies are very closely related mutations of the original virus they were infected with. Over time the diversity of quasispecies increases and may affect response to treatment.

Do Genotypes Play a role in Disease Progression?This is still a controversial area. Many studies have shown genotype 1, especially type 1b to be associated with more advanced liver disease, however these patients are generally older and have a longer duration of infection. Poynard et al assessed factors associated with fibrosis progression in a large study involving 2,235 patients. No link was found between genotype and fibrosis progression.

What about Genotypes and Treatment?Research has shown people with genotypes 2 or 3 have a higher sustained response rate (60-70%) to combination therapy than genotype 1 (20-30%). However other factors such as stage of fibrosis or cirrhosis, viral load, age, gender, duration of disease and excessive alcohol consumption also influence response to therapy.

Furthermore the duration of treatment is also influenced by genotype. Previously untreated patients with genotype 1 double their chance of a sustained response when treated for 12 months instead of 6 months. Conversely 12 months treatment for patients with genotypes 2 or 3 does not improve response rates over 6 months treatment.

Can Genotypes be used in studying the Modes of Transmission?Genotyping has been used to study the ways hepatitis C is transmitted. It has been used to identify the source of infection in cases of patient-to-patient transmission and is also useful in the study of other modes eg. vertical (mother to baby), sexual transmission and needle stick injury.

Prevalence of HCV Genotypes in US Population By Boyle, MD

In order to better characterize genotypic variants, which may be important for defining more effective treatment options for chronic hepatitis C virus (HCV) infection, greater than 81,000 patient results were analyzed at one laboratory in the U.S.

The investigators found that the most prevalent genotypes in the U.S. were 1 (57,653, 71.0%), 2 (11,588, 14.3%), and 3 (9,416, 11.6%), followed by a less common type 4 (1,375, 1.7%). Each of the remaining types represented less than 1% of the population; however, unlike other rare genotypes, the prevalence of group 6 was quite significant (1,197, 1.5%) and when the overall prevalence of this genotype in the U.S. is calculated this would mean that up to 60,000 HCV-infected individuals have this genotype.

Finally, the investigators found that the prevalence of each genotype in the population was relatively stable over the time period 1999 to 2002.

The authors conclude, “In the United States up to 4 million people are infected with HCV. If the results of our study are applied to this number, group 6 genotypes may represent. Therefore, there is a compelling need to consider the less common genotypes, particularly those of group 6, for inclusion into future clinical studies.”

9-17-03

ReferenceTE Schutzbank and others. HCV Population Study in the U.S.: an Incentive for Further Clinical Trials. Abstract: V-775. Abstracts of the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy. September 14-17, 2003. Chicago, IL.