Understanding Hepatitis C Genotypes


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The hepatitis C virus (HCV) mutates frequently, resulting in a wide variety of virus types. The different types of HCV vary according to their genetic structure. Some HCV variations, which are referred to as "quasispecies," are very similar in genetic makeup, sharing most of the same genetic code. However, other variations are more diverse, sharing only 60 to 70 percent of the same genetic code. These more diverse variations are classified as HCV genotypes.

To date, researchers have identified at least six major HCV genotypes, which are represented by numbers followed by small letters – for example, 1a, 1b, 2a, etc. While a patient infected with HCV may have several quasispecies of the virus, he or she has only one genotype.

The distribution of HCV genotypes changes over time and varies by geographic region and among specific groups of people. From 1960 to 1969, the most prevalent HCV genotype in the United States was type 1b, accounting for 47 percent of cases. From 1980 to the present, type 1b prevalence dropped to 12 percent of cases in the United States. This shift might have be due to the reduction of HCV transmission through blood transfusion, which occurred in the late 1980s, when the blood supply began to be more accurately screened for HCV.

In a review of 42 patients infected with HCV in the United States in the 1980s to the present, 55 percent had type 1a, 12 percent had 1b, 19 percent had 2a or 2b, and 14 percent had 3a or 4a. Patients infected with HCV through blood transfusions are more likely to have type 1b. In industrialized countries, patients infected through IV drug use are more likely to be infected with type 1a and 3a.

Some researchers have theorized that certain HCV genotypes, particularly 1b, are associated with a more aggressive disease course and a more rapid progression to cirrhosis. However, several studies have failed to back this up. This theory will remain inconclusive until future research clearly defines the natural disease course of HCV, along with the role genotypes play in influencing prognosis.

What is currently known is that a patient’s response to interferon therapy does appear to be influenced by genotype. Patients infected with type 1a and 1b appear to have lower overall response rates to interferon therapy. This means that they are less likely to exhibit lower liver enzyme levels and a reduction of viral count from the treatment. In the future, higher doses of interferon may prove more beneficial in such patients, although this has not yet been recommended by the FDA.

Which HCV genotype a person has can be determined by lab tests, such as a polymerase chain reaction (PCR) that determine the genetic sequence of organisms. However, genotype testing is currently a research tool and not part of the routine management of patients with HCV. Which HCV genotype a person has does not presently influence treatment options, and treatment with interferon should not be withheld due to the person's genotype.

"Chronic Hepatitis C Infection in the U.S.: An Insight Into the Natural History And Evidence For A Change In the Epidemiology of HCV Genotypes," N.N. Zein, et al., Hepatology, Oct. 1996, p. 150A.
"The Interferon Sensitivity Determining Region: All Hepatitis C Virus Isolates Are Not the Same," David Herion andJay Hoofnagle, Hepatology, Vol 25, No 3, March 1997, pp 769-770.
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