How Hepatitis C Affects the Liver
In chronic hepatitis C (HCV) infection, HCV enters the cells of the liver. This triggers an immune response, resulting in inflammation. In most cases of HCV infection, the body’s immune system is not able to get rid of the virus by itself. Without antiviral treatment, HCV-related inflammation of the liver persists, causing scarring of the liver called fibrosis. Eventually, areas of scarring become interconnected and the texture of the liver itself changes. Over time, fibrosis can progress to an advanced stage called cirrhosis. With extensive fibrosis (cirrhosis), blood is no longer able to flow through the liver and liver function becomes significantly impaired.1
Your immune system and HCV
The job of our immune system is to defend the body from invasion by foreign substances or organisms, such as bacteria or viruses like HCV. Think of the redness and swelling you experience when you get a splinter in your finger. Your immune system reacts to the splinter and the bacteria that enter the body with it by sending a range of immune system cells to the site of invasion or injury to fight infection. These cells produce chemicals that serve as tools in fighting the invasion. The inflammation at the site of the splinter is a sign that your immune response is working.
The same thing happens when your immune system detects invasion by HCV. It mounts an attack both inside and outside of infected liver cells (hepatocytes). Inside hepatocytes, various immune system cells and chemicals, including natural killer (NK) cells and substances called cytokines, interferons (IFN), interleukins (IL), and growth factors, mount an attack on the virus. At the same time, another immune response is also being launched outside of hepatocytes by a group of immune system cells that patrol the body and go to the site of invasion to respond to the invader. Included in this group are white blood cells (also called leukocytes, from the Greek words, leukos for white and cytes for cells). These leukocytes include B and T lymphocytes (B- and T-cells, for short). B-cells specialize in generating antibodies against a specific antigen (an invader) and are designed to fight invasion that occurs outside of cells. T-cells, of which there are two main types: helper T-cells (Th cells) and killer T-cells, specialize in neutralizing antigens (this is a term used for a foreign microorganism) that invade the fluid inside the cell (intracellular fluid), where B-cells are not effective.2
When the immune system encounters HCV, specialized cells called macrophages bring the antigen to B-cells and also display part of the antigen to circulating Th cells (T helper cells). The antigen is “fingerprinted” by the B-cell and this information is used to develop an antibody, a protein (called an immunoglobulin [Ig]) that specializes in attacking that antigen. Th cells also closely examine the antigen and determine whether they should stimulate production of B-cells for antibody production or stimulate production of killer T-cells. Killer T-cells are produced if the antigen has invaded cells. The killer T-cell attaches itself to an infected cell and in most cases destroys that cell.
Liver damage related to HCV
The damage that HCV causes starts when the virus enters the cells of the liver (hepatocytes). When a virus enters the body, it needs to find a place where it can reproduce or replicate in order to survive. HCV can enter a number of different cells in the body for this purpose. However, hepatocytes are the key site for replication. When HCV enters a liver cell, it uses the chemicals in that cell to help it reproduce and generate copies of itself. It releases these new copies into the bloodstream and they travel to other liver cells to begin the cycle of replication again. The process of reproduction inside a liver cell can result in cell damage or destruction to the cell. However, most of the damage to hepatocytes (and the fibrosis that develops because of it) occurs because of the body attempting to fight invasion by HCV. When the body detects an invader such as HCV, the immune system launches an immune response, sending many different cells and chemical to the site of infection to destroy the virus. In the process of this attack, infected cells are often destroyed along with the virus.1
Inflammation of the liver, which characterizes HCV infection, results from the immune response to HCV invasion. Because HCV is good at staying ahead of the immune system, the immune response is seldom successful at eliminating the virus from the body. Instead, an insufficient immune response continues, resulting in chronic inflammation. Liver cells are destroyed in the process of this immune response and, over time, fibrosis progresses.1
How does fibrosis form in HCV?
Fibrosis or scarring results when liver cells are destroyed due to HCV infection. Fibrosis is the formation of excessive connective tissue that builds up in the liver due to injury resulting from chronic inflammation. Fibrosis itself may have no symptoms. However, it can lead to decreased blood flow through the liver and impaired liver function. Eventually, areas of scarring become interconnected and the texture of the liver itself changes. Over time, fibrosis can progress to an advanced stage called cirrhosis. With extensive fibrosis (cirrhosis), blood is no longer able to flow through the liver and liver function becomes significantly impaired.1
- Friedman SL. Pathogenesis of hepatic fibrosis. Uptodate. Runyon, BA, Travis AC, eds. Accessed at: www.uptodate.com. 2014.
- Spengler U, Nischalke HD, Nattermann J, Strassburg CP. Between Scylla and Charybdis: the role of the human immune system in the pathogenesis of hepatitis C. World J Gastroenterol 2013;19:7852-66.