A hepatitis C genotype refers to the type, or strain, of the virus you have contracted. Genotypes may not play a role in the progression of the virus, but they help in developing a treatment plan.

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Hepatitis C virus (HCV) is a viral infection that causes inflammation of the liver.

According to the Centers for Disease Control and Prevention (CDC), seven HCV genotypes and more than 67 subtypes have been identified.

In this article, Dr. Kenneth Hirsch, who has extensive clinical practice working with people who have HCV, answers common questions about HCV genotypes.

HCV is a single-stranded RNA virus, which means the genetic code of each virus particle is contained within one continuous piece of the nucleic acid RNA.

Every strand of nucleic acid (RNA or DNA) is made up of a chain of building blocks. The sequence of these blocks determines the proteins an organism requires.

Unlike HCV, the human genetic code is carried by double-stranded DNA. The human genetic code goes through strict proofreading during the process of DNA replication.

Random changes (mutations) to the human genetic code occur at a low rate because most mistakes in DNA replication are recognized and corrected.

In contrast, HCV’s genetic code isn’t proofread when it’s replicated. Random mutations occur and stay in the code.

HCV reproduces very quickly — up to 1 trillion new copies per day. So certain parts of HCV genetic code are highly varied and change frequently, even within a single person with an infection.

Genotypes are used to identify particular strains of HCV. They’re based on differences in particular regions of the viral genome.

Additional branching subcategories within a genotype include subtypes and quasispecies.

The different HCV genotypes and subtypes have different distributions throughout the world:

  • Genotypes 1, 2, and 3 are found worldwide.
  • Genotype 4 occurs in the Middle East, Egypt, and Central Africa.
  • Genotype 5 is present almost exclusively in South Africa.
  • Genotype 6 is seen in Southeast Asia.
  • Genotype 7 has recently been reported in the Democratic Republic of Congo.

Genotype 1 is the most common HCV genotype in the United States. It’s found in nearly 75% of all HCV infections in the country, according to the U.S. Department of Veterans Affairs.

Most of the remaining people in the United States with HCV infection carry genotypes 2 or 3.

All HCV genotypes could be transmitted through blood, such as during injections, tattooing, and blood transfusions.

Genotypes used to play a more important role in determining the best type of treatment and predicting its outcome.

For example, a combination of ribavirin and pegylated interferon (PEG) was an effective treatment for HCV genotype 1 but not genotypes 2 and 3.

Sometimes a combination of different treatments may be used to help treat specific genotypes.

Traditionally, anti-HCV therapy was a combination of PEG and ribavirin, which targets your immune system to help it recognize and eliminate cells affected by HCV.

Now, HCV treatment for genotypes 1 to 6 most commonly involves using a combination of direct-acting antiviral (DAA) drugs.

DAAs target the virus by using small molecules designed to inhibit the specific viral proteins responsible for the reproduction of HCV in your body.

The two most common DAA treatments are:

  • glecaprevir (300 milligrams [mg]) and pibrentasvir (120 mg)
  • sofosbuvir (400 mg) and velpatasvir (100 mg)

These are known as simplified treatments, which are for people who do not have cirrhosis and have not previously received HCV treatment.

The Food and Drugs Administration (FDA) has approved 11 DAAs for the treatment of HCV. If you have decompensated cirrhosis, a doctor may refer you to a hepatologist to discuss other treatment options available.

DAAs could cure HCV in up to 95 out of 100 people, according to the World Health Organization (WHO).

How long does HCV treatment last?

The duration of your treatment will depend on the HCV genotype you have and your treatment plan.

With PEG/ribavirin treatment alone, HCV used to require up to 48 weeks of treatment. With the development of DAAs, HCV may be treated in 8 to 12 weeks.

No, not anymore.

Due to the effectiveness of newer DAA treatments, all genotypes have a recovery rate of 95% in people without decompensated cirrhosis.

Each of HCV’s essential proteins works the same, regardless of genotype. However, small mutations may cause these essential proteins to be structurally different.

Because these proteins are essential for the HCV life cycle, the structure of their active sites is least likely to change due to random mutation. A protein’s active site is also relatively consistent between different genotypes.

How well a particular DAA works is affected by where it binds to the target protein. The effectiveness of those agents that bind most directly to the protein’s active site is least likely to be affected by the virus genotype.

All DAAs suppress ongoing HCV replication, but they do not eject the virus from its host cell or remove infected cells. The immune system does this job.

Several variables may affect the type of treatment your doctor prescribes, such as whether you:

  • have decompensated or compensated cirrhosis
  • have hepatitis B or hepatocellular carcinoma (liver cancer)
  • are pregnant
  • have received a liver transplant

Possibly.

Some research suggests genotypes 1 and 3 are associated with higher rates of cirrhosis and hepatocellular carcinoma than other genotypes.

However, it’s important to note the progression of liver damage is slow and often happens over decades.

If you receive an HCV diagnosis, your doctor will most likely assess you for liver damage. Liver damage is an indication for therapy.

The risk of developing liver cancer doesn’t appear to be related to HCV genotype. In chronic HCV infection, hepatocellular carcinoma only develops once cirrhosis has been established.

If your treatment is successful before developing cirrhosis, then the infecting genotype isn’t a factor. That said, if you have already developed cirrhosis, some data suggests genotypes 1b or 3 may increase the risk of cancer.

Screening for liver cancer is recommended for everyone who has HCV with cirrhosis. Some doctors recommend more frequent screening for those with genotypes 1 and 3.

What is the hardest genotype of hepatitis C to cure?

Limited research exists on the specific success rates for treating HCV genotypes 5, 6, and 7. That said, some research suggests genotype 3 is least likely to respond to newer treatments like DAAs.

How long does a hepatitis C genotype test take?

HCV genotypes are usually determined by a blood test, according to the CDC. The blood test itself will take a few minutes. Results may take anywhere from 20 minutes to a few weeks, depending on the type of blood test you receive.

What is the most resistant HCV genotype?

Research suggests genotype 1a is the most resistant to some types of DAAs.

HCV genotypes refer to the type of HCV infection you are affected by.

There are seven genotypes with many subtypes.

It’s important for a healthcare professional to determine your genotype, as this will help them develop a treatment plan that’s right for you.


Dr. Kenneth Hirsch earned his doctor of medicine from Washington University in St. Louis, Missouri. He did postgraduate training in both internal medicine and hepatology at the University of California, San Francisco (UCSF). He did additional postgraduate training at the National Institutes of Health in allergy and immunology. Dr. Hirsch also served as the chief of hepatology at the Washington, D.C., VA Medical Center. Dr. Hirsch has held faculty appointments at the medical schools of both Georgetown and George Washington Universities.

Dr. Hirsch has extensive clinical practice serving patients with the hepatitis C virus. He also has years of experience in pharmaceutical research. He has served on advisory boards for industry, national medical societies, and regulatory bodies.