Understanding the body’s immune responses to HIV and HBV co-infection

A new study published in Hepatology, part-funded by the Medical Research Foundation, reveals novel insights around immune responses to HIV-HBV co-infection. These findings could lead to improved and earlier treatment options for patients infected with hepatitis B.

Why is research into hepatitis B important?

The vast majority of viral hepatitis-related deaths are specifically caused by hepatitis B, one of just a few viruses that can cause chronic infections in humans, persistently damaging the liver over time.

While antiviral therapies for hepatitis do exist, they are non-curative, and current treatments don’t target hepatitis B virus (HBV) particles in the liver. There is an urgent need to develop more effective treatment options for HBV.

Dr Upkar Gill, from Queen Mary University of London, is making vital progress in this field. In this new study, Dr Gill and his team observed novel immune responses in patients infected with both HIV and HBV, compared to those infected with only HBV.

HIV and HBV co-infection

Many HIV patients undergo chronic HBV co-infection due to the shared transmission routes of the two viruses – i.e., both can be passed through contact with the blood or bodily fluids. When infected with both viruses, it is thought that patients often see an accelerated impact of chronic HBV symptoms, leading to faster end-stage liver disease and cancers.

At the cellular level, both viruses lead to dysregulation of the immune system. Specifically, the viruses create changes in natural killer (NK) cells, which are responsible for destroying infected cells and therefore integral to the body’s natural immune system.

In this work, led by both Dr Gill and Dr Dimitra Peppa (University College London), the team carried out in-depth cell analysis of blood samples from patients undergoing anti-viral therapy at The Royal London, Royal Free Hospital & Mortimer Marker Centre. The researchers conducted high-throughput single-cell analysis on immune NK cells from the blood, to ascertain their composition and function.

Understanding the immune cell landscape in both patient groups

The team uncovered a key difference in the make up of NK cells between these two distinct patient groups – they observed an ‘adaptive’, less exhausted signature of NK cells in people with HIV-HBV co-infection. In other words, patients with the co-infection exhibited lower levels of immune cell dysfunction compared to those with only HBV.

The findings also revealed that people with HBV mono-infection presented higher circulating levels of the hepatitis B surface antigen (HBsAg) and HBV RNA - which reflects higher disease activity in the liver and a higher disease burden than those with the co-infection of HIV and HBV.

Dr Gill explains, “We previously believed that people infected with the two viruses would have a more ‘exhausted’ immune phenotype with progressive disease. However, on the contrary, our findings show that people with HBV mono-infection in fact exhibit an unfavourable disease profile.”

It is likely that the less exhausted immune phenotype in co-infection is due to starting antiviral therapy earlier, which should now be strongly advocated for HBV mono-infected patients too.

Dr Gill’s study provides the foundations required to carry out further work on NK liver cells for these two patient groups. He adds, “The results from this study provide a springboard to modify treatment guidelines for HBV mono-infection, with the notion to offer earlier therapy to improve clinical outcomes.

“NK-cell focussed immune therapies are being used for various cancers and immune conditions at present. There is potential to tailor NK-cell directed methods to advance HBV cure strategies in the future as well.”

Read the full paper: 10.1097/HEP.0000000000000877