This week, a group of interdisciplinary researchers from the University College London (UCL) released study findings in which they made a discovery that could have important implications in several clinical disciplines. The study entitled, “Metabolic regulation of hepatitis B immunopathology by myeloid-derived suppressor cells,” focused on the reasons why the immune system cannot control hepatitis B virus (HBV) infection once it becomes established in the liver, and the findings could potentially lead to new therapeutic drug targets to treat HBV infections. The study was published in the latest edition of Nature: Medicine.
About the Hepatitis B Virus
The HBV is a major risk factor for developing liver cancer (LC). LC is the second most common cancer worldwide, with 700,000 new cases diagnosed each year; approximately 33,000 of which will occur in the U.S. The virus is easily transmittable through blood and infected bodily fluids, as well as a high rate of perinatal (mother to child during birth) transmission. According to the CDC, the global burden of HBV includes 240 million people chronically infected and an estimated 786,000 deaths each year.
About the Study
The study was conducted in the laboratory of Dr. Mala Maini, PhD, Deputy Head of the Department of Immunology, Professor of Viral Immunology, Division of Infection & Immunity, UCL. Dr. Maini’s laboratory research aims are focused on dissecting the immune system components of chronic viral infection and liver damage in order to allow the development of novel immunotherapeutic strategies for HBV.
In a University press release, Dr. Maini explains her lab’s previous work and how it relates to this study, “Hepatitis B patients usually don’t have symptoms for decades, so can carry the virus unknowingly and can spread it through childbirth, sexual contact or contaminated needles. Our work has shown that during this ‘silent phase’ of infection, specialized suppressor cells switch off the immune response by cutting off its food supply. This is one of the many ways the liver protects itself from inflammation and immune damage but at the same time, prevents elimination of pathogens like hepatitis B. If we could boost the immune system and counteract the liver’s suppressive effect, then the infection could potentially be cleared after a large ‘burst’ of immune activity. This might cause short-term damage to the liver, but would prevent the long-term damage from scarring and liver cancers that we see in chronic patients.”
To understand why the immune system cannot control HBV infection once it becomes established in the liver, Dr. Maini and her colleagues compared blood samples from 138 chronic hepatitis B patients and 99 healthy controls; they also looked at liver tissue samples from 42 patients.
The findings showed that during the silent phase of infection patients had high levels of cells called granulocytic myeloid-derived suppressor cells (gMDSCs) that accumulated in the liver. The gMDSCs suppress T cells (immune cells) by cutting off their food supply.
In an explanation about the meaning of the findings, Dr. Laura Pallett, PhD, Professor Division of Infection & Immunity, UCL, and lead study author, stated, “The gMDSCs suppressed both the T cells that fight hepatitis B virus and those that cause inflammation in the liver. So patients with more gMDSC tended to have less liver damage but were unable to control hepatitis B virus. Women had higher levels of gMDSC than men, which fits with their threefold lower risk of developing liver inflammation from hepatitis B.”
Dr. Maini agreed with her colleague and added, “If these cells can prevent immune cells from damaging the liver in hepatitis B patients, perhaps they could help to prevent immune rejection of transplanted livers. Similarly, such suppressor cells could potentially be harnessed to protect specific organs from damage in patients with autoimmune diseases.”