Understanding Hepatitis C Genotypes

Reviewed by: HU Medical Review Board | Last reviewed: March 2015.

If you have been diagnosed with hepatitis C (HCV) infection, your doctor will test you to determine the genotype of the virus that you have. Genotype means genetic variation in the DNA of the virus.1 There are 7 major hepatitis C genotypes and numerous subtypes of the virus.2 The major HCV genotypes respond differently to different treatment regimens, including different medications and dosing schedules. So, HCV genotyping is important in determining which medications will be most likely to help you and how long those medications should be taken.1

What are the hepatitis C genotypes?

HCV genotypes

Genotype 1
  • Most common genotype in US and Europe
  • Important subtypes: 1a and 1b
Genotype 2
  • Less common than genotype 1 in US and Europe
  • Important subtypes: 2a and 2b
Genotype 3
  • Most common in India, the Far East, and Australia
Genotype 4
  • Most common in Africa and the Middle East
  • Is emerging in Europe among drug users and other high-risk populations
Genotype 5
  • Most common in South Africa
Genotype 6
  • Most common in Hong Kong, Vietnam, and Australia
Genotype 7
  • Unspecified location

Understanding mutations of hepatitis C genotypes

In addition to the different hepatitis C genotypes and subtypes, there are also quasispecies (different versions) of the virus. After HCV infects the liver, the virus is constantly reproducing or making copies of itself. This happens on an almost unimaginable scale, with trillions of individual viruses replicating every day. As viruses replicate, some of the copies they make contain errors or mutations in their genetic code. Sometimes, a mutation results in a quasispecies of HCV that is successful at evading the body’s immune system. The immune system is constantly trying to catch up with the HCV virus as it produces slightly different versions of itself. Once the body has successfully eradicated an HCV quasispecies, another takes its place. Experts believe that this process of mutation and quasispecies development is the reason why so many people who are infected with HCV develop chronic disease and why infection is so difficult to cure. This also may be why it is so difficult to develop a vaccine against HCV.3

Where are the different hepatitis C genotypes found?

HCV has evolved over time into 7 distinct genotypes (some experts believe there are more), with at least 67 subtypes. Hepatitis C genotypes are distributed throughout the world, with some genotypes (e.g., genotype 1 in the US and Europe) being predominant in certain geographic areas. HCV genotype 1 is the most common genotype in the US and Europe, accounting for 60% to 70% of HCV. HCV genotype 1a is more common than 1b in the US. 3

Hepatitis C genotypes 1 and 3 infection are associated with more aggressive liver disease, with increased risk for cirrhosis and fibrosis, as well as greater risk for hepatocellular carcinoma. After genotype 1, HCV genotype 2 is the next most common HCV genotype in the US, where it accounts for approximately 10% of cases. HCV genotypes 3-6 are more common in Africa, the Middle East, the Far East, India, and Australia. Genotype 7 has only been isolated in a limited number of cases. Genotype 3 is associated with increased risk (3-times higher versus other genotypes) for development of fatty liver disease (steatosis). 1,4

Hepatitis C genotypes are substantially different from one another in their genetic make-up, which explains why each genotype responds differently to antiviral treatments.1,4

How is genotype determined?

A simple blood test can be used to determine your hepatitis C genotype. The test doesn’t have to be repeated because once someone has been infected with HCV, the genotype remains the same. It is possible to be infected by more than one HCV genotype. However, this occurs rarely.

Learn more about recommended treatment based on HCV genotype.

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