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CiiM and MHH study investigates biomarkers to predict the success of treatment
Hepatitis B is a viral infection of the liver that can lead to liver cirrhosis and hepatocellular carcinoma. Antiviral therapies can suppress the infection, but a functional cure is rare. Novel immunotherapies should lead to an actual cure more frequently. However, it is still unclear which patients benefit most from these new therapies. Researchers at the Centre for Individualised Infection Medicine (CiiM), a joint Facilities or Institutions of the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), as well as the MHH and the German Center for Infection Research (DZIF), have now identified a biomarker that should enable predictions about the success of the therapy. The results have been published in the journal Gut.
It is estimated that more than 250 million people worldwide are chronically infected with the hepatitis B virus. Cytotoxic T cells and T helper cells play an important role in the fight against viral infections. The constant activation of these immune cells in chronically infected people leads to their exhaustion in the long term. However, their ability to be activated is a prerequisite for benefiting from immunotherapies. Infected liver cells are also induced by the virus to produce large quantities of hepatitis B surface protein complexes ("hepatitis B surface antigen", HBsAg). Antibodies bind to these proteins, which further weakens the immune response. HBsAg is therefore currently assumed to be a decisive factor for the impaired immune response and is used to stratify patients for new treatment options.
In the current study, the team led by Prof. Markus Cornberg and PD Dr. Anke Kraft examined the T-cell response of patients with a chronic hepatitis B virus infection. Cornberg, Deputy Director of the Clinical Department of Gastroenterology, Hepatology, Hepatases and Endocrinology at the MHH, heads the "Infectiology with a Focus on Hepatology" working group at the CiiM together with Kraft, is Clinical Director of the HZI and Deputy Coordinator of the "Hepatitis" research area at the German Center for Infection Research (DZIF). The researchers found that the T-cell responses were not associated with the HBsAg level in the blood, but were rather influenced by the age of the patients. "Younger patients, who have presumably not been chronically infected with the virus for so long, show a stronger T-cell response to the virus," says Cornberg. "As this is a prerequisite for successful immunotherapy against the virus, new immunotherapies should primarily be investigated in these patients."
The team also looked for alternative biomarkers in order to be able to make therapy predictions. They found that the T cells of infected patients with a low blood level of another viral marker ("hepatitis B core-related antigen", HBcrAg) had better immune function. "Our study shows us factors that we can use to identify patient groups in which immunotherapy may be particularly promising," says Kraft. New methods to treat infectious diseases individually are also the goal of the research of Prof. Yang Li, Co-Director of the CiiM and Head of the Department "Bioinformatics of Individualized Medicine" at the HZI, who was also involved in the study. She says: "For many infectious diseases, we can achieve better therapeutic success if we take individual differences into account. With the biomarker that we are describing in this study, we are taking a step in this direction in hepatitis B therapy."
Text source (author): Charlotte Wermser / HZI
Original publication:
Elmira Aliabadi, Melanie Urbanek-Quaing, Benjamin Maasoumy, Birgit Bremer, Martin Grasshoff, Yang Li, Christian E Niehaus, Heiner Wedemeyer, Anke R M Kraft, Markus Cornberg. Impact of HBsAg and HBcrAg levels on phenotype and function of HBV-specific T cells in patients with chronic hepatitis B virus infection. Gut Published Online First: October 26, 2021. doi: 10.1136/gutjnl-2021-324646
Comment on the publication:
Bertoletti A, Boni C. HBV antigens quantity: duration and effect on functional cure. Gut. 2021 Nov 19:gutjnl-2021-326258. doi: 10.1136/gutjnl-2021-326258. Online ahead of print. PMID: 34799373
- http://dx.doi.org/10.1136/gutjnl-2021-326258