When acute hepatitis develops into chronic hepatitis
Researchers at the Helmholtz Centre in Braunschweig demonstrate how the immune system reacts to a hepatitis B infection
Hepatitis B is the most prevalent infectious disease in the world. It results in either an acute infection or, in rare cases, it can develop into a chronic disease. Researchers at the Helmholtz Centre for Infection Research (HZI) in Braunschweig have now examined the way in which the immune system reacts differently to both chronic and acute hepatitis B. To achieve this, Carlos A. Guzmán, Head of the “Vaccinology and Applied Microbiology” working group and Robert Geffers, Head of the “Gene Expression Analysis” platform, examined the incidence and species of special defence cells, T helper cells, along with their role in the development of the disease in conjunction with their Indian colleagues. With the aid of genetic analysis, they showed how the genes in these immune cells are regulated differently according to the development of the disease. These new results can help doctors to discover whether an infection is curable or whether by settling in the liver, it will develop into a chronic case. These results are now published in the scientific journal, “Hepatology”.
Approximately 300 to 420 million people (5 to 7% of the world’s population) have a chronic hepatitis B infection. India is one of the countries, in which hepatitis B is very common. A differentiation is made with the development of the disease between acute and chronic hepatitis B. The most common symptom of an acute infection is jaundice. In 5% of the infections, the disease becomes chronic, that is to say, the viruses remain in the liver. If left untreated, chronic hepatitis B can lead to a change in consciousness, cirrhosis and cancer of the liver. Until today scientists have not fully understood the role that the immune system plays in characterising an acute or chronic hepatitis B infection.
A decisive factor in achieving an appropriate immune reaction is the quick mobilisation of immune cells. These specifically attack the infected liver cells without destroying any unnecessary liver tissue in the process. Subspecies of the T helper cells play a decisive role in achieving this necessary balance between immunological defence and tolerance: effector T cells and regulatory T cells (Treg). Whilst the effector T cells fight a virus infection and kill off the infected host cells, the Treg cells shut down an immune reaction and cut off the effector T cells. They counteract any destruction of the tissue.
The international team of research scientists examined how these T helper cells influence the development of the hepatitis B disease. To this end, they took blood samples from Indian patients with hepatitis B and compared the extent to which the altered incidence of the T cell subsets in the blood influences the development of the illness and which genes are responsible for this.
Guzman’s and Geffers’s teams were able to show that, with acute hepatitis B, the effector T cells are extremely active and destroy infected host cells. Treg cells prevent effector T cells damaging healthy liver tissue during this stage of the infection. On the other hand, T effector cells are largely inactive with chronic hepatitis B infections: the Treg cells prevent an immune reaction and, in doing so, increase the number of hepatitis B viruses that are able to live in the organ. The immune system’s constant struggle against the virus leads to a slow destruction of the liver tissue. The researchers checked their observations with gene activity: They demonstrated that more that one hundred genes in effector T cells are regulated differently in an immune reaction to acute hepatitis B than to a chronic case.
“The molecular mechanisms and the specific gene activities of a hepatitis B infection were unknown up until now. We now have a much better understanding of how acute and chronic hepatitis B infections develop and which processes are involved”, says Carlos A. Guzmán. “With gene analysis we are able to further investigate the molecular links, which, in many ways, are a reason for the clinical observations”. The doctor thus has an opportunity to improve his diagnosis with so-called “marker genes” and to improve his treatment of the patients with targeted, immunotherapeutic measures”, says Robert Geffers, who conducted the gene analysis of the blood tests.
Article: Nirupma TrehanPati, Robert Geffers, Sukriti, Syed Hissar, Peggy Riese, Tanja Toepfer, Jan Buer, Manoj Kumar, Carlos A. Guzman, Shiv Kumar Sarin. Gene expression signatures of peripheral CD4+ T cells clearly discriminate between patients with acute and chronic hepatitis B infection. Hepatology 2009. DOI 10.1002/hep.22696