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Hepatitis C versus the Immune System: The Biology of Hepatitis C Transmission

September 5, 2018

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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 its 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.


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.5-9


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.

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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.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



Related: Hepatitis C: How Is It Transmitted and Who Should Be Tested?



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

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Related Stories

Hepatitis C: How Is It Transmitted and Who Should Be Tested?
An Overview of Hepatitis C Transmission and Prevention
Overview of HCV Disease Progression



This article was provided by Canadian AIDS Treatment Information Exchange. It is a part of the publication Prevention in Focus: Spotlight on Programming and Research. Visit CATIE's Web site to find out more about their activities, publications and services.

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