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Antiviral therapy of chronic hepatitis B virus infections: is resistance still a challenge?

Published on August 30, 2011 Archived on January 30, 2022   62 min

A selection of talks on Pharmaceutical Sciences

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0:00
I am Professor Fabien Zoulim and I am the head of the Liver department at the Civil de Lyon and Hepatitis Research Laboratory at INSERM U871, located in Lyon. Today, I will try to give you another view on the antiviral therapy of chronic hepatitis B virus infection and we will see with HPV resistance is still a challenge for therapy.
0:29
Chronic Hepatitis B virus infections remain a major public health problem. Indeed, the World Health Organization estimates that more than 300 million people are chronic carriers of that virus despite the availability of an efficient vaccine. Chronic hepatitis B remains the first cause of primary liver cancer, also called hepatocellular carcinoma. In the last decade, there was major progress in the treatment of chronic hepatitis B with the development of potent nucleoside and nucleotide analogs. The goals of antivirals therapy are to obtain viral suppression, which is a identified by undetectable HPV DNA viral real-time PCR assays and to achieve remission of liver disease. However, the treatment of chronic hepatitis B remains a clinical challenge because viral eradication is not yet possible.
1:38
The natural history of liver damage in chronic hepatitis B is a result of the interplay between viral replication in infected parasite and the host immune response against the infected cells. It's a measure of phases of natural history of the disease are depicted on this slide. The first phase of the chronic hepatitis B infection is the immuno-tolerant phase. It is characterized by high viral load and identified by the positivity of HBe antigen and high HPV DNA levels with normal ALT levels in the serum. This is usually associated with minimal liver disease or minimal chronic hepatitis. This is followed by the immunoreactive phase, where the immune system's kicks in and tries to kill infected cells, try to eradicate the infection. There is an equilibrium between the rate of cell killing and the rate of viral replication. Chronic liver lesions can occur. This is characterized by decreasing HPV DNA in the serum because of the number of infected cells that are killed by the immune system which is associated by rising ALT levels. This defines a chronic hepatitis phase where a liver biopsy may show moderate to severe chronic hepatitis. These patients are at risk of developing liver cirrhosis. In this phase, treatment is indicated when the immune system can take over or when antiviral treatment is efficient. This phase is followed by the inactive phase associated with a low replication level. Usually, HBe antigen and becomes negative, and anti-HIV antibodies seroconversion occurs. HBV DNA levels are below 2,000 international units per mL and ALT levels become normal. This is associated with a remission of liver disease and usually, even the biopsy shows inactive diseases. Also, the state may occur at a stage of advanced fibrosis or cirrhosis. Since the virus can persist in the liver then this phase may be followed by a reactivation phase; whereas the level of HPV DNA may go up again, as well as ALT levels. In this phase, we can observe moderate to severe chronic hepatitis, which may be associated with liver cirrhosis. Again, in this phase, treatment is indicated. After prolonged infection, often after dictates of chronic HPV infection and occult infection may occur where HBS antigen may become undetectable and HPV DNA may be detected only in the liver. This occult infection may be associated with severe disease.
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Antiviral therapy of chronic hepatitis B virus infections: is resistance still a challenge?

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