September 30, 2022

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Hepatitis B: A few copies of cccDNA are enough to start HBV

Hepatitis B: A few copies of cccDNA are enough to start HBV

 

Hepatitis B: A few copies of cccDNA are enough to start HBV. Global researchers of hepatitis B are concerned that a few copies of cccDNA are enough to start HBV.

The doctors of medicine and chemistry who are responsible for the new drug project of hepatitis B around the world have different concerns. For example, some experimenters will pay attention to the role of cccDNA in maintaining the persistence of HBV and causing the progression of liver disease. In fact, cccDNA is the template for all HBV mRNA, and a few copies of cccDNA in each liver are enough to restart HBV infection.

 Hepatitis B: A few copies of cccDNA are enough to start HBV 

 

Global researchers are concerned about hepatitis B, a few copies of cccDNA are enough to start HBV

The main characteristic of patients with chronic hepatitis B is weak innate immunity and HBV-specific immune response. In order to help patients with chronic hepatitis B regain their immunity, researchers in related fields worldwide have considered TLR agonists, engineered T cells, immune checkpoint inhibitors, and therapeutic vaccines. It seems that the new immunomodulator may have fewer side effects than interferon, but more data is needed to prove its clinical advantage in eliminating serum hepatitis B surface antigen.

Still connected to the previous topic, the functional cure of HBV infection, the current mainstream thinking of global researchers is that it may come from a combination of new drugs that work through different mechanisms. The combination of directly targeting the hepatitis B virus life cycle and inducing host immunity may be the most effective. Of course, these drug development ideas require further research to prove their safety and effectiveness. On the whole, the long-term efforts of global scientific researchers for the functional cure of chronic hepatitis B have been reported with high enthusiasm and expectations.

Hepatitis B: A few copies of cccDNA are enough to start HBV

We return to the original intention of HBV treatment, or call it the goal. The development of drugs for the treatment of chronic hepatitis B virus infection-related hepatitis. These drugs should ultimately be able to reduce the risk of CHB developing cirrhosis and liver-related complications, including hepatocellular carcinoma.

At present, among the viral markers, HBV-DNA suppression (i.e. virological response), and chronic hepatitis B patients with positive and negative hepatitis B e antigen, their e antigen or surface antigen seroconversion, are currently mainly used to measure HBV The effectiveness index of treatment.

However, researchers have found that although virological and serological reactions strongly reduce the probability of liver cirrhosis and liver cancer, there is still a residual risk. So, back to the beginning, some global hepatitis B drug project leaders are more concerned about the role of cccDNA in maintaining the continuity of HBV and causing the progression of liver disease. It is the root of hepatitis B virus.

What does functional cure of HBV mean? That is, continuous non-drug-inhibited serum hepatitis B surface antigen and seroconversion into anti-HBV antibodies (HBsAb). This sentence means that hepatitis B surface antigen clearance must be met, with or without hepatitis B surface antibodies, but at this time Although cccDNA is still continuously in transcriptional activity.

Hepatitis B: A few copies of cccDNA are enough to start HBV

What does it mean to completely cure HBV? That is, continuous non-drug seroconversion into HBsAb, which is related to the eradication of cccDNA and completely eliminates hepatitis B virus from the body. The two tools introduced earlier can be used to accurately determine whether the cure is complete. They are cccDNA and serum HBV-RNA. HBV-RNA can be easily diagnosed by the laboratory and is widely used. There are currently approved drugs, how much effect can they achieve? Existing drugs mainly refer to pegIFN and NAs.

Many medical journals around the world have their research and development process, namely preclinical research and phase III clinical trial data. After these data are on the market, it has been further proved that they can achieve the virological response of chronic hepatitis B, and in a few cases, it can also achieve a serological response. Although they may partially inhibit the transcription of established cccDNA, they cannot prevent the initial formation of cccDNA after hepatocyte reinfection.

 

At present, researchers around the world are not fully aware of the reasons for the decline of cccDNA during the development and application of NAs. However, scientific opinions have been proven: pegIFN can directly mutate the deaminase APOBEC and destroy the hepatitis B virus cccDNA.

 

(source:internet, reference only)


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