Hepatitis C versus the immune system: the biology of hepatitis C transmission

Prevention in Focus PiF 2018 Fall

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In this article, we follow the journey of hepatitis C – from when a person is exposed to the virus to the development of a chronic infection and then onto cure. We explore how the hepatitis C virus can get in the body, and what it does once it's inside. We also look at how the body tries to stop the infection and when it is successful at defeating the virus. If the body’s response to the virus is unsuccessful, a chronic hepatitis C infection results.

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What fluids are implicated in hepatitis C transmission?

For someone to get hepatitis C there must be an exposure to the hepatitis C virus. This exposure occurs when body fluids from someone with hepatitis C that contain enough virus for transmission to occur, get into the blood of another person. The primary body fluid that is responsible for hepatitis C transmission is blood. This occurs by direct blood-to-blood contact. Hepatitis C virus has also been found in the semen and rectal fluid of some men with hepatitis C and HIV.

Hepatitis C virus has been isolated in semen and rectal fluid,1 menstrual fluid,2,3 vaginal fluid,4 saliva5 and breastmilk,6 which means there is a theoretical risk for hepatitis C transmission. However, the risk of transmission through these fluids is very low to non-existent.5,6,7,8,9

What happens if exposure occurs?

If a person is exposed to a body fluid that can pass the hepatitis C virus, it still needs to be able to get into the body for a person to get an infection. Our bodies are covered in skin and mucous membranes, which act as a protective layer that won’t allow hepatitis C to enter the body. For the virus to get into the body there needs to be a break in the skin or one of the mucous membranes.

In Canada, the most common way for hepatitis C to be passed is through a break in the skin. This predominately happens by injecting drugs with a needle (or reusing other drug use equipment) that has already been used by someone with hepatitis C.10 Hepatitis C was also commonly passed through blood transfusions in Canada prior to the introduction of hepatitis C blood supply screening in 1992.

A less common way that hepatitis C can enter the body is through the mucous membranes. This predominantly occurs among men who have sex with men during condomless anal sex. The virus is thought to get into the body through a tear in the delicate mucous membrane of the rectum or a sore caused by a sexually transmitted infection (STI) such as a syphilis ulcer. During sex, the virus can be passed into the rectum on a penis, hand (during fisting) or sex toy that has been in contact with blood (or possibly semen or rectal fluid containing hepatitis C).11

How common is hepatitis C transmission?

An estimated 220,697 to 245,987 Canadians were living with chronic hepatitis C in 2011. That is the equivalent of six to seven people out of every 1,000 Canadians (or 0.6% to 0.7% of the total Canadian population).12

Of the estimated 332,414 people who have ever had hepatitis C in Canada in 2011, 43% were people who used injection drugs and 35% were people from countries where hepatitis C is endemic,12 such as countries in central Asia and central sub-Saharan Africa.13 The main mode of transmission in these populations is blood-to-blood contact, either through the use of shared drug use equipment or through medical procedures in countries other than Canada, including the use of unscreened blood or unsterilized equipment. These two routes of transmission account for over three quarters of hepatitis C infections in Canada.

The sexual transmission of hepatitis C accounts for a more limited number of transmissions in Canada. Sexual transmission of hepatitis C is mainly occurring among HIV-positive gay and bisexual men, but also to a lesser degree in HIV-negative gay and bisexual men.14,15 A systematic review found that in industrialized countries the prevalence of hepatitis C was 8.3% in HIV-positive gay and bisexual men and 1.5% in HIV-negative gay and bisexual men.14 The most common factor in the sexual transmission of hepatitis C is condomless anal sex. The receptive partner (bottom) in condomless anal sex has a higher risk for the sexual transmission of hepatitis C then the insertive partner (top).16

There are several factors that have been found to increase the risk of sexual transmission of hepatitis C in gay and bisexual men:11,17

  • having receptive condomless anal sex
  • sharing sex toys
  • fisting without a glove
  • having multiple sex partners
  • engaging in rough sex
  • anal douching
  • having HIV
  • having an ulcerative STI (such as syphilis)
  • using recreational drugs before or during sex

A review of the literature on sexual transmission in monogamous heterosexual serodiscordant couples (where one of the partners has hepatitis C) found no increased risk of hepatitis C transmission.18 There was an increased risk of transmission with heterosexual couples who had multiple sex partners but this was most likely due to couples also using injection drugs. Finally, the presence of an STI or HIV also increased the risk of the sexual transmission of hepatitis C in heterosexual couples.18

The transmission of hepatitis C through perinatal transmission (during pregnancy and shortly after birth) is low. According to a meta-analysis, transmission of hepatitis C through vertical transmission is around 5.8%.19 Vertical transmission can happen during both pregnancy and delivery.7

What happens once the hepatitis C virus is in the body?

Once the hepatitis C virus is in the body it travels through the bloodstream to the liver. How the virus gains entry to a liver cell is not fully understood but the virus uses at least two of its own proteins (called E1 and E2) and several receptors on the liver cell to gain entry.20,21 Once inside the cell, the virus uses different parts of the cell’s machinery to make copies of (or replicate) its genetic material (RNA) to create new hepatitis C viruses.21 These new viruses leave the liver cell to enter other liver cells and continue to replicate.22 Replication of the virus occurs rapidly at first before the immune system is able to respond, resulting in high levels of the virus. This rapid replication slows abruptly when the body’s immune system starts to respond to try to control the virus.23

Very soon after the hepatitis C virus enters the body, the immune system attempts to stop the virus from replicating through a complex response involving many different immune cells and proteins.

The body’s immune response to hepatitis C virus

This immune response is not fully understood. What we do know is that at first the immune system detects the virus in the liver cell as foreign matter and responds by producing many proteins, including interferons. These proteins are able to slow down virus production in the cell but not stop it.23 Some of the proteins attract immune cells, called natural killer cells, which are able to identify and kill the virus-infected cells.

After approximately six to eight weeks, the immune system is able to better figure out how to identify the hepatitis C virus and launches a more targeted response.24 Some of the body’s immune cells (called B cells) start to make hepatitis C antibodies, which identify and bind to the hepatitis C virus. These antibodies are like a flag that help other immune cells (called CD8 T-cells) find and destroy the hepatitis C virus before they can infect other cells.25 More immune cells, called CD4 cells, are also critical in the immune system fight because they support the B cells and CD8 cells to maintain their responses.25

While the immune system is trying to fight and destroy the hepatitis C virus, the virus is trying to stop or evade the immune system’s attack on it. One way the virus does this is by mutating.24 Errors in the replication process cause mutations in the genetic material of the virus. It can make up to 1,000,000,000,000 mutations per day.26 Some of these mutations may affect the shape of proteins on the surface of the virus. As a result, in some people, the CD8 cells, whose job it is to find and destroy cells containing the hepatitis C virus, cannot identify the virus because it has mutated and changed. This slows down the destruction of infected liver cells by the CD8 cells.26,27

During the fight between the immune system and virus, the amount of the virus will fluctuate. If the immune system is able to remain strong – and the virus is not able to evade the immune system by mutating – it will be more likely to eliminate (or clear) all of the hepatitis C virus in the body. This is called spontaneous clearance, and occurs during the first six months of infection. The majority of people (approximately 75%) will not experience any signs or symptoms in these early stages of infection and may not be aware they had a hepatitis C infection and have successfully cleared the virus.28,29 The other 25% of people may develop yellowing of their eyes or skin during acute infection. If the immune cells become exhausted, the body is not able to destroy the virus and the infection becomes a chronic hepatitis C infection.30

How many people can clear the virus on their own (spontaneous clearance)?

Based on six studies in a recent international meta-analysis, 19.8% of people cleared the virus from their body within three months; 27.9% within six months; and 36.1% within 12 months. After two years, the percentage of people who cleared the virus only increased by 1% (37.1%).31

One of the studies used in the analysis consisted of data from nine cohorts from Canada, Australia, the Netherlands and the USA. The combined 12-month clearance rate from this study was 27.4%, a lower rate than that found in the meta-analysis.29

Who is more likely to clear the virus on their own?

The international meta-analysis31 identified groups of people that are more likely to clear the virus on their own:

  • Women are 1.5 times more likely than men to clear the virus on their own.
  • Indigenous people are 2.1 times more likely than non-Indigenous people to clear the virus on their own.
  • People with a symptomatic infection are 2.6 times more likely to clear the virus than those with an asymptomatic infection.
  • Black people are 2.6 times more likely than non-Black people to clear the virus.
  • Younger people (less than 45) are 1.9 times more likely to clear the virus than older people.
  • People who do not have HIV are 2 times more likely to clear hepatitis C than people with HIV.
  • People with hepatitis B are 4.2 times more likely to clear hepatitis C than people who do not have hepatitis B.
  • Those with hepatitis C genotype 1 virus are 1.6 times more likely to clear the infection than individuals with other hepatitis C genotypes.
  • People who do not use excess alcohol are 1.5 times more likely to clear the virus compared to people who use excess alcohol.
  • People who have no history of injecting drug use are 1.7 times more likely to clear the virus compared to people who have a history of injecting drug use.

What happens during chronic hepatitis C infection?

Having hepatitis C in the body causes liver cells to die. It is unclear whether the hepatitis C virus or the immune system kills the liver cells. It is likely a combination of both factors, with the immune system causing the most injury. Liver cells that are infected with hepatitis C virus release signals that tell immune cells to come to the liver cells. These immune cells kill the virus-infected cells, but the death of the liver cells results in an inflammatory response in the liver. The end result of this inflammatory process is scarring in the liver because damaged tissue is not able to repair itself properly.32

For most people, liver injury progresses slowly. People will develop scarring in their liver, and over time this scarring will increase and more of the liver will become injured. This is called fibrosis. Fibrosis can be measured using a scale of F0 to F4, with F0 being no liver fibrosis to F4 being an advanced level of liver injury known as cirrhosis. It can take 20 to 30 years to develop cirrhosis or liver cancer but in some people it can happen more quickly.33

Is there a cure for Hepatitis C?

Hepatitis C treatment with direct-acting antiviral medications (DAAs) cures most people with the virus. Treatments are simple to take, have few side effects and are usually taken for 12 weeks or less. If a person is cured through treatment it means the virus is no longer in their body. The earlier that someone is treated, the less likely they are to develop advanced liver damage.

When a person is cured, the liver damage usually stops progressing and the liver will begin to heal in some people.34 This is less likely to happen for people who have advanced cirrhosis.35 For a small proportion of people who are cured of hepatitis C, the liver continues to become injured and progresses to cirrhosis. This is usually linked to other factors such as alcohol use or fatty liver disease.34 Being cured of hepatitis C decreases the likelihood of a person getting liver cancer, liver failure or dying from liver problems.36 People with advanced liver disease will need to be followed up with regular ultrasound scans after cure because there is still a risk of liver cancer developing. There are also many non-liver related health benefits from being cured of hepatitis C, including a reduced risk of diabetes mellitus, mixed cryoglobulinaemia (a blood disorder), glomerulonephritis (a type of kidney disease), porphyria cutanea tarda (a build up of chemicals that affects the skin and nervous system), and possibly non-Hodgkin lymphoma (a cancer that starts in blood cells).37

Being cured of hepatitis C does not give a person immunity. A person can become infected again if they are exposed to the hepatitis C virus.

Key messages for service providers

Encourage people to practise safer drug use, safer sex and other prevention strategies

Service providers can support people who inject, snort or inhale drugs to prevent them from getting hepatitis C by encouraging them to use new equipment every time they use drugs.

Service providers can support gay and bisexual men who are vulnerable to the sexual transmission of hepatitis C by encouraging them to:

  • use a new condom for each partner
  • use a new glove each time for fisting
  • use a new condom on sex toys for each partner
  • use individual lube containers
  • use their own drug use equipment and don’t share it
  • get tested regularly for other STIs

Service providers can support people who get tattoos and piercings to use a professional studio with proper sterilizing equipment, such as an autoclave. For people who are getting tattoos and piercings outside professional studios encourage them to have the artist use a sterile tattoo machine and as much new equipment as possible.

Service providers can also encourage people to not share personal care items, such as razors, toothbrushes and nail clippers.

Encourage people to get tested for hepatitis C

People at ongoing risk for hepatitis C – such as people who inject, snort or inhale drugs, and gay and bisexual men who have condomless sex – should be encouraged to speak to their healthcare provider about how often they should get tested. Service providers can offer testing to immigrants and newcomers from countries where hepatitis C is endemic. The CCHIR tool can help determine if screening is appropriate.

Explain that testing requires two different tests, a hepatitis C antibody test for screening and a hepatitis C RNA test to confirm if someone has a hepatitis C infection. Two RNA tests separated by at least six months may be required to confirm a chronic infection.

If a baby is born to a pregnant person with hepatitis C, the baby can be tested for hepatitis C antibodies 12 to 18 months after they are born. If they are tested at 12 months a follow up test should be done at 18 months. Antibody testing prior to 18 months is not perfect because the test may detect antibodies from the parent that were transferred to the baby during pregnancy but are not the baby’s own antibodies. If the parents are anxious about their child having hepatitis C, a hepatitis C RNA test can be done two months after the birth. If the child tests positive for RNA there is still a chance of them clearing the virus, so follow up RNA testing will need to be done every six months. If the child tests negative for hepatitis C RNA, an antibody test can be done at 12 or 18 months. Testing prior to 18 months does not change the management of hepatitis C in children.7

Link people with chronic hepatitis C to treatment

If a client is diagnosed with chronic hepatitis C, share the good news about how effective, manageable and accessible hepatitis C treatment is. It cures over 95% of people who take it, causes few side effects, is usually taken for 12 weeks or less, and is simple to take. All provinces and territories have programs that cover all or most of the cost of treatment.

It is also important to let people know that if they have cleared the virus on their own or been cured through treatment, they can get infected again if they are re-exposed so it is still necessary to take steps to prevent getting hepatitis C again.

Service providers can play a key role in supporting individuals and communities most affected by hepatitis C through advocating for testing, treatment and prevention strategies.

 

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About the author(s)

Scott Anderson is currently studying to become a nurse. Prior to this, he was CATIE's hepatitis C researcher/writer and a research coordinator at the Centre for Addiction and Mental Health.