Mechanism of action of interferon in the treatment of chronic hepatitis B

  Interferon is a multifunctional protein (biologically called a cytokine) that is produced when the body is infected by a virus. We’ve all had influenza, and when you have a fever, muscle and joint aches all over your body, and general weakness, you feel the presence of interferon. Of course there are other cytokines involved as well, but interferon is one of the most prominent cytokines produced during viral infections. If you have ever had an interferon injection, your doctor will tell you that you will have “flu-like symptoms” after taking interferon because the symptoms of the flu are actually caused by interferon.  Interferon is a multifunctional protein that is an important part of the body’s natural immune system.       In general, interferon has the following important roles: 1. antiviral effect. When our body is infected with a virus, the body will produce a large amount of interferon.  2, anti-proliferative effect. This is the reason why interferon can be used to treat many kinds of tumors.  3, immunomodulatory effect. Interferon is part of natural immunity, but interferon is also involved in a variety of specific cellular immunity, such as enhancing the expression of infected hepatocytes to express proteins recognized by T lymphocytes, helping T cells to recognize virus-infected cells, etc.  4. Anti-fibrotic effect. This is why liver fibrosis is significantly better in patients treated with interferon.  In addition, interferon has a variety of functions such as anti-neovascular proliferation and promotion of apoptosis. However, in the treatment of chronic hepatitis B, the antiviral effect and immunomodulatory effect, as well as the anti-fibrotic effect may be the main.  How does interferon work? Does interferon need to “break through the hepatocyte membrane”?  Interferon does not need to break through the hepatocyte at all. Interferon must bind to the interferon receptor on the cell surface in order to exert its biological effects.  Interferon has antiviral, immunomodulatory, and antifibrotic effects, but these effects are not achieved by the direct action of interferon itself, but by binding to receptors on the cell surface and transmitting “signals” from the cell surface to the nucleus, where it activates a series of genes and expresses a series of proteins that exert the effects of interferon. Interferon activates these proteins to carry out the function of interferon.  Interferon binds to interferon receptors located on the cell surface and transmits the interferon signal to the nucleus, where it activates the genes that interferon is intended to activate, resulting in the expression of a series of proteins that perform interferon functions. The two most important and iconic proteins are PKR and 25OAS, which in turn activate the production of other proteins with specific functions to achieve antiviral or immune enhancing effects. For example, through PKR, interferon can stimulate cells to produce an RNA enzyme that, when produced in the cell, can directly hydrolyze viral RNA or single-stranded DNA, directly reducing viral production. The interferon-activated protein can also interfere with the assembly of the virus within the cell, causing a decrease in the amount of virus. More importantly, interferon can stimulate infected cells to produce marker proteins on the cell surface, which facilitates immune cells to recognize infected hepatocytes and will help cytotoxic T lymphocytes to remove the infected hepatocytes when entering the immune clearance phase and together with the cccDNA. This effect of viral clearance through immune enhancement is what fundamentally distinguishes interferon from nucleoside analogs. Interferon also promotes apoptosis of infected hepatocytes through a series of proteins that it activates, among others. In addition, there are still many unexplored aspects of interferon that need to be further clarified so far.  In summary, the binding of interferon to interferon receptors on the cell surface is the key for interferon to exert its biological effects. When active interferon binds to the interferon receptor, it exerts antiviral and antiviral immune enhancing effects by activating a series of proteins. Interferon stimulates cells to produce a variety of direct antiviral proteins that directly inactivate or hydrolyze the virus. More importantly, it enhances antiviral immune function to achieve lasting suppression of the virus.  However, interferon cannot help if the patient’s own immunity is not activated and the patient does not enter the immune clearance phase. It must be activated by the body’s cellular immunity against the hepatitis B virus before it can fully play its role. To use a figurative analogy, “a star fire can start a prairie fire”, this star fire has to be lit by the patient himself, once there is a star fire, interferon can help start a prairie fire. It is also like a car to run must first fire, fire and then refuel the car will run up. “It is up to the patient to start the fire, and interferon can play a role in fueling the car.  In contrast to nucleoside analogues, the greatest effect of interferon is the activation of the patient’s autoimmunity, and after a limited course of treatment, a durable response after discontinuation of the drug is achieved. A small number of patients can even turn surface antigens negative and surface antibodies positive, achieving the ultimate cure.