A new study to combat chronic hepatitis B

A new study to combat chronic hepatitis B

Publication date: 22-02-2024

Updated on: 22-02-2024

Topic: Research

Estimated reading time: 1 min

Over 300 million people worldwide are affected by the chronic form of hepatitis B, one of the leading risk factors for liver cirrhosis and liver cancer. In patients with this chronic infection, the immune system fails to eradicate the virus responsible for the disease, which continues to survive and reproduce within liver cells. A group of researchers from Vita-Salute San Raffaele University, through close collaboration with the American start-up Asher Biotherapeutics, has tested a molecule capable of reactivating the immune system against chronic hepatitis B for the first time in the world in preclinical models.

The findings published today in the prestigious scientific journal Science Translational Medicine lay the groundwork for the development in the clinic of an immunotherapy for this serious disease. 

The study was coordinated by Professor Matteo Iannacone, director of the Division of Immunology, Transplantation and Infectious Diseases at San Raffaele Research Hospital, who returned to Italy after a long research experience in the United States, supported by a Career Development Award from the Armenise-Harvard Foundation.

Hepatitis B virus and current therapies

Hepatitis B virus (HBV) is transmitted: 

  • by contact with infected blood;
  • by the sexual route;
  • from mother to child during childbirth. 

Unlike when an adult contracts the virus, more than 90% of infants infected at birth develop the chronic form of hepatitis B. 

In patients with the chronic form of infection, the immune system fails to eradicate the virus responsible for the disease, which continues to survive and reproduce within liver cells.

There currently exists a preventive vaccine for the disease, but infected patients cannot benefit from it. Scientific research is progressing significantly in the field of antivirals, for which San Raffaele is an international benchmark.

The research of Matteo Iannacone's group, in close collaboration with the unit headed by Professor Luca Guidotti, deputy scientific director of the Institute, has in fact contributed in recent years to the development of some of the antivirals commonly used today to treat the disease in its chronic form.

How to awaken the immune system: the San Raffaele’s proposal

Why does the immune system remain ineffective and how can it be awakened? This question has already been addressed by scientists in a research published in Nature in 2019. The researchers demostrated how through molecular analysis using intravital microscopy techniques that T lymphocytes (cells of the immune system deputed to attack the HBV virus) fail to eradicate the infection and are dysfunctional from the moment they are activated.  

The work on characterizing dysfunctional T lymphocytes also enabled researchers at San Raffaele to identify molecules that were more suitable and effective in awakening these cells. Among them is interleukin-2, a molecule-messenger of the immune system that acts as a kind of immunotherapy, which has already been successfully tested both in cultured cells obtained from patient samples and in the animal model. 

Interleukin-2, unfortunately, when administered systemically, produces serious side effects: it increases the permeability of blood vessels, causing severe edema. This happens because the molecule is not only able to reach its target, T lymphocytes, but also acts on Natural Killer cells, which induce toxicity, and in addition on regulatory cells that inhibit the immune response.

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