Different Genotypes of Hepatitis C

What is Hepatitis C and its Genotypes?

Hepatitis C is a viral infection that leads to inflammation of the liver. The hepatitis C virus (HCV) is transmitted through blood. In some rare cases, the virus can also be transmitted through sexual contact. (1)

There are six genotypes of HCV, labeled 1 through 6. A genotype of the HCV is used to categorize the virus based on similar genes. It is, therefore, essential to understand the various HCV genotypes because treatment of the disease depends on which genotype of the virus you have.

There are also some subtypes of the virus that are labeled with letters. For example, genotypes 1a and 1b. People commonly get infected by a single dominant genotype, but in some cases, a person can get infected by more than one genotype of the virus at the same time. This is referred to as a mixed infection. (2)

Once you receive a diagnosis of hepatitis C, your doctor will then work towards determining the type of HCV you have so that you can get the best treatment for hepatitis C.

Different HCV Genotypes and Importance of HCV Genotypes

HCV genotypes are based on differences in various regions of the viral genetic code or genome. There are also additional subcategories within each genotype. These are known as subtypes and quasispecies.

According to the US Centers for Disease Control and Prevention (CDC), there are at least six different HCV genotypes and over 50 subtypes that have been identified to date. (3)

These different genotypes and subtypes of the virus are known to be found in different distributions throughout the world. For example, genotypes 1, 2, and 3 of HCV can be found worldwide. However, genotype 4 typically occurs in the Middle East, Egypt, and central Africa. Genotype 5 is present in South Africa, and genotype 6 can be observed across Southeast Asia.

Genotype 1 is the most common type of HCV genotype that can be found in the US, and it is found in almost 75 percent of all HCV infections that occur in the country. The remaining percentage of the infected population in the US carry genotypes 2 and 3.

The genotype of HCV is not consciously related to the rate of liver damage, or even the chances of developing cirrhosis. However, identifying the HCV genotype can help doctors predict the outcome of treatment.

The genotype of the virus can also help predict the outcome of any anti-HCV therapy that is undertaken with interferon-based treatments. Genotype also plays a role in determining treatment. For example, in specific treatment formulations, the recommended dosage of ribavirin and pegylated interferon (PEG) are for those who have particular HCV genotypes.

Latest Research on Genotypes and Specific Treatments

The most commonly used treatment for hepatitis C is PEG/ribavirin. However, this therapy does not target the actual virus itself. This treatment focuses on affecting the patient’s immune system, and its goal is to activate the immune system into recognizing and eliminating the cells that are infected with HCV. However, there are individual variations of HCV in some people who do not appear like the virus to the immune system. This is one of the reasons why in certain patients, HCV infections tend to persist and then turn into chronic infections.

In spite of the genetic diversity, researchers have nevertheless still identified specific proteins that are necessary for the virus to reproduce in the body. These proteins are present in almost all of the many variants of HCV. The newer treatments for HCV, therefore, focus on targeting these proteins. This means that they specifically target and eliminate the virus. For example, direct-acting antiviral (DAA) therapy makes use of smaller molecules that are specifically designed to inhibit these viral proteins. (4)

The last decade has witnessed the development of several DAA drugs, and each of these drugs targets one of the essential HCV proteins. The first two DAA drugs were boceprevir and telaprevir. Both of them target a type of HCV enzyme known as protease. These drugs are today used in combination with PEG/ribavirin therapy.

Both these DAA drugs are highly effective for genotype 1 HCV, moderately effective for genotype 2, and not effective at all in genotype 3.

Newer DAA drugs have been approved for use in combination with PEG/ribavirin. These newer medications target many additional HCV proteins. One of these newer drugs is known as sofosbuvir. (5)

When PEG/ribavirin therapy was being used as a standalone treatment, it was observed that genotype 1 HCV used to take the longest time to get treated and also had the least likelihood of success. When used in combination with sofosbuvir, genotype 1 HCV is now totally curable in more than 90 percent of patients who have been treated for just 12 weeks. (6)

The US Food and Drug Administration (FDA) has also approved the very first interferon-free combination therapy for treating HCV infections. This is a combination of ribavirin and sofosbuvir. This new therapy is prescribed for 12 weeks in patients with genotype 2 or 24 weeks in patients with genotype 3 HCV.

Does the Genotype Affect the Likelihood of Developing Liver Cancer or Cirrhosis?

There is some research (7) that indicates that people who are infected with genotype 1 of HCV, especially those with subtype 1b, have a higher risk of liver cirrhosis as compared to those infected with other genotypes of the virus. Regardless of this, though, there is not much of a change in the recommended treatment plan.

The progression of liver damage in HCV infections is slow and happens over many years. So, anybody who has recently been diagnosed with HCV should be checked for liver damage, and then the level of liver damage should be taken as an indication for determining therapy.

When it comes to liver cancer, the risk of it does not appear to be related to any one particular HCV genotype. For example, in chronic HCV infection, liver cancer only happens once liver cirrhosis is firmly established. If a patient is treated effectively before they develop any damage to their liver, then the infecting genotype of HCV is no longer a factor.

However, in patients who already have cirrhosis, some research shows that HCV genotypes 1b or 3 could increase the risk of developing liver cancer. (8)

Conclusion

Screening for cirrhosis and liver cancer is recommended for anyone who is diagnosed with HCV. Many doctors also recommend more frequent testing for people who are infected with genotypes 1 and 3 of HCV. While the treatment for hepatitis C is now simpler, safer, and far more effective than before, it is still recommended that you live a healthy lifestyle to prevent getting infected with HCV in the first place.

References

  1. Poynard, T., Yuen, M.F., Ratzin, V. and Lai, C.L., 2003. Viral hepatitis C. The Lancet, 362(9401), pp.2095-2100.
  2. Zein, N.N., 2000. Clinical significance of hepatitis C virus genotypes. Clinical microbiology reviews, 13(2), pp.223-235.
  3. Cdc.gov. (2019). Hepatitis C Questions and Answers for Health Professionals | CDC. [online] Available at: https://www.cdc.gov/hepatitis/hcv/hcvfaq.htm [Accessed 21 Oct. 2019].
  4. Foster, G.R., Irving, W.L., Cheung, M.C., Walker, A.J., Hudson, B.E., Verma, S., McLauchlan, J., Mutimer, D.J., Brown, A., Gelson, W.T. and MacDonald, D.C., 2016. Impact of direct acting antiviral therapy in patients with chronic hepatitis C and decompensated cirrhosis. Journal of hepatology, 64(6), pp.1224-1231.
  5. Sulkowski, M.S., Naggie, S., Lalezari, J., Fessel, W.J., Mounzer, K., Shuhart, M., Luetkemeyer, A.F., Asmuth, D., Gaggar, A., Ni, L. and Svarovskaia, E., 2014. Sofosbuvir and ribavirin for hepatitis C in patients with HIV coinfection. Jama, 312(4), pp.353-361.
  6. Spach, D.H., AETC, M.W. and Coffey, S., Learning Objective Performance Indicators.
  7. Medscape. (2019). Predicting Progression to Cirrhosis in Chronic Hepatitis C Virus. [online] Available at: https://www.medscape.com/viewarticle/460551 [Accessed 21 Oct. 2019].
  8. Nkontchou, G., Ziol, M., Aout, M., Lhabadie, M., Baazia, Y., Mahmoudi, A., Roulot, D., Ganne‐Carrie, N., Grando‐Lemaire, V., Trinchet, J.C. and Gordien, E., 2011. HCV genotype 3 is associated with a higher hepatocellular carcinoma incidence in patients with ongoing viral C cirrhosis. Journal of viral hepatitis, 18(10), pp.e516-e522.

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