Institute of Immunity and Transplantation


Understanding immunity to tackle liver diseases

Find out about Professor Mala Maini's research on understanding immunity to tackle liver diseases.

The liver is a common organ for transplantation, a frequent site for tumours and the niche where 3 of the most prevalent and devastating human pathogens (hepatitis B, hepatitis C and malaria) replicate.

Liver disease due to viruses, alcohol and fat is the only cause of mortality still increasing in the UK, due to their capacity to trigger chronic damage leading to fibrosis, cirrhosis and liver cancer. We dissect mechanisms by which the immune response can control or exacerbate liver disease by studying hepatitis B virus infection.

HBV is a small (3200 nucleotide) DNA virus that is hepatotropic and non-cytopathic. Liver disease results from the immune responses it triggers. One third of the world have been infected and approximately 350million remain persistently infected, causing around 600,000 deaths a year.

Hepatitis B paralyses host immunity by a combination of: longstanding high antigen load: patients are often infected from birth with extremely high viral loads and the production of huge amounts of viral antigen; and taking advantage of the tolerising properties of the liver environment.

For example, we recently discovered that natural killer cells (NK cells), that are present in very large numbers in the liver, can kill HBV-specific T cells through the TRAIL pathway - a form of fratricide (Peppa et al. Journal of Experimental Medicine 2013). By blocking these pathogenic interactions between NK cells and T cells we could recover an enhanced antiviral response to HBV. Insights such as this inform the development of novel immunotherapies for liver diseases like hepatitis B.