Hepatitis C Genetics

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There's not just 1 type of Hepatitis C (HCV). There are 11. Well, actually, there are more.

Why does this matter?

What type of HCV helps determine which drugs are taken, for how long, and how successful the treatment will be.

How many types are there?

There are actually 11, though 6 are the primary viruses we see. These 11 major genotypes, in turn, may have many different subtypes.

In the US, there are HCV genotypes 1–6 and over 50 subtypes.

Who gets which types?

Genotypes 1-3 are the most common and are found around the world.

Most infections are due to type 1 (1a and 1b), which make up 3 out 5 infections.Type 1a is mostly found in the US, Canada, Mexico, and Northern Europe. Type 1b is more common in Southern and Eastern Europe as well as Japan. 

Type 2 is found in North America, Europe and Japan (subtypes 2a and 2b), as well as Italy (2c) and West Africa.

Type 3 is more common in south-east Asia, especially India.

Type 4 is found mostly in the Middle East and central Africa.

Type 5 is found largely in South Africa.

Types 6-11 are found in Asia. They are generally not found in other parts of the world.

What does this mean?

  • Treatments are chosen - and even developed - for different genotypes. 
  • Some drugs can only be used in certain genotypes.
  • Some drugs haven't been tested in certain rarer genotypes.
  • Some drugs have different success rates in different genotypes.
  • Some drugs have to be used with particular other drugs in certain genotypes. (In particular, some patients don't need to take interferon which is hard for many patients to take.)
  • Some treatment regimens can vary in length depending on which genotype is present. (Twice as long for some genotypes)
  • Overall, genotype 2 has responded better to treatment.

    Treatment is now able to create a “sustained virological response” to rid the body of hepatitis C, a cure. This treatment takes weeks or years, but after that, a patient should be free of the virus.

    Recently, there have been advances in genotype 1 treatment. It was the most common type in the US and much of the world. It used to be hard to treat genotype 1. Now more and more treatments  have been tested and tailored to genotype 1. As more and more drugs have been approved since 2014, there are more options of successful treatment to get rid of Hepatitis C.

    Hep C treatment, especially genotype 1, used to require injections. This involved shots of interferon and ribavirin pills - both of which can have side effects that are very hard for many. Hep C treatment though is moving on from these drugs.

    Recently, new pills have been approved to treat Hepatitis C, focusing on genotype 1. For instance, the pill Sofosbuvir (Sovaldi) was relatively recently approved. Originally, this pill still had to be taken with an injection of pegylated interferon and ribavirin for those with genotype 1 and 4.

    There is now, however, a drug approved that combines sofosbuvir with ledispavir, Harvoni, which does not require interferon or any injections. This combination drug, unfortunately, is very expensive.

    There are many pills now newly available for genotype 1. These include in addition to ledipasvir-sofosbuvir, another combination pill ombitasvir-paritaprevir-ritonavir, as well as dasabuvir, simeprevir, and sofosbuvir, which have all been approved by the FDA for genotype 1, as well as daclatasvir (not approved for type 1 but sometimes used as well). (Simeprivir does not work as well if a certain mutation is present in subtype 1a).

    These new drugs add as well to the treatment options available for non-genotype 1 HCV. The drug Sofosbuvir, even without the development of Harvoni, could be used without interferon for those with genotypes 2 and 3. In addition, Daclatasvir pill was recently approved for use with sofosbuvir for the treatment of chronic genotype 3 infection. Simeprevir has also been used in some places for genotype 4

    Other relatively new drugs are being discontinued as the development of Hep C drugs has advanced so rapidly.

    There are subtypes, too?

    Yes, 1a and 1b are subtypes of genotype 1. There are likewise, subtypes 2a, 2b, 2c. There are multiple other subtypes - at least 50 in all - for the various different genotypes.

    Is this it? Or are there more types?

    HCV is an RNA virus. HCV produces more HCV by using a viral photocopier - an RNA-dependent RNA polymerase - which doesn't have spellcheck. There is no error check when copies of HCV are made by HCV. This means there is a lot of variation, sometimes within a patient, between different copies of Hepatitis C.

    With all these new Hepatitis C copies produced, there develops quasi species -  a "complex mixture of genetically distinct but closely related variants". These different types of Hep C can affect how successfully the body can respond to and suppress Hepatitis C.

    Can genotypes be tested for?

    Yes, a blood test can test for what genotype a patient has. Unless there is a repeat exposure and reinfection, retesting is not needed as then genotype stays constant.

    Can there be more than 1 genotype?

    Yes, someone can be infected with more than 1 genotype. It is not that common, but it does happen.

    There are 4 different ways for this to happen.

    Reinfection occurs when a first infection completely clears and then a second infection occurs.

    Dual Infection happens when 2 types infect someone at the same time, such as from use of blood products derived from multiple donors (like hemophiliacs may, in particular, have).

    Coinfection is when 2 infections occur at the same time or within a brief period of time before infection with one strain is fully established. This happens when the second exposure is during the primary infection phase of the first. This is the period when the first immune response is made to HCV right after initial exposure to the infection. This may happen if needles are shared between multiple people and strains are passed in a very narrow time window.

    Superinfection happens when a second infection occurs after the first infection is established. This occurs during when there is already a persistent infection, after the primary phase of infection. One strain may then predominate.

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