Taking us closer to a cure for chronic hepatitis B

Thanks to your support, we’ve funded life-saving research into this disease. Dr Upkar Gill from Queen Mary University is investigating the immune and viral outcomes of treatments in patients with chronic hepatitis B. This work could lead to much-needed new therapies for this serious condition.

What is chronic hepatitis B?

“The hepatitis B virus is a DNA virus that, once infected, replicates in liver cells,” Upkar explains. “The viral particles or DNA are released into the blood, which is how we detect the infection.”

When a person is first infected with the hepatitis B virus, it is referred to as an ‘acute’ infection.

Upkar adds, “Over 90% of adults can clear the infection without treatment, due to a good natural immune response. Chronic infection is diagnosed when two blood tests, taken six months apart, measure the presence of what’s called a ‘surface antigen’ of hepatitis B. This is a substance which triggers an immune response in the body.

“We see most chronic infections in children or newborns, who haven’t been vaccinated. The replication of the virus in chronic infections can cause inflammation, leading to serious consequences such as scarring, cirrhosis, and eventually, liver cancer.

“Unfortunately, symptoms are so rare that people often feel fine until the disease is quite advanced. Detecting hepatitis B without blood tests is nearly impossible, so the goal is to stop the disease spreading before scarring occurs, so that patients can live as normally as possible.”

Investigating the body’s immune response to infection

In most cases, when the body detects a virus, natural killer (NK) cells serve as one of the first lines of defence. NK cells are a type of immune cell, or white blood cell. They can recognise unfamiliar substances and work directly to kill virally infected or tumour cells, either by engulfing them or releasing particles that cause their death.

NK cells are present in the blood and circulate throughout the body, including the liver and other organs, while some reside in tissues to provide localised defence.

“Sometimes, however, NK cells can mistakenly attack healthy cells,” Upkar explains. “This causes inflammation.”

Harnessing natural killer immune cells to target hepatitis B

In hepatitis B infections, immune cells play a critical role in controlling the virus. NK cells, in particular, contribute significantly to this process by destroying infected liver cells.

“The problem is that NK cells can’t always distinguish between infected and healthy liver cells, leading to collateral damage. We want the immune cells to focus on killing infected liver cells, while leaving healthy ones intact.”

Upkar therefore set out to explore populations of NK cells. He wanted to determine whether there are adaptive or healthy NK cells that could be harnessed for potential therapies to treat HBV infections.

“We wanted to see if certain treatments could boost these NK cells and maintain their effectiveness in combatting the virus, without becoming exhausted themselves.”

To test their theories, the Queen Mary University team, in collaboration with colleagues at UCL, compared chronic HBV infection with HBV-HIV co-infection, finding specific properties in NK cells that could be vital to target.

“We also noticed that hepatitis B infection alone might be more inflammatory than co-infection of both HIV and HBV, because we’re not treating it early enough.

“We’re also exploring the impact of metabolic conditions, like cardiovascular disease, on hepatitis B outcomes. Our work suggests that earlier treatment overall could help to mitigate inflammation and the impact of all these co-occurring factors.”

Through detailed investigations of NK cell populations, Upkar and his team are taking us one step closer to effective treatments for chronic hepatitis B.

“Our work could lead to new therapies that boost the right type of immune cells, while minimising liver damage.”

“We’re also exploring how to reduce liver inflammation caused by the immune response to viral clearance, possibly by modifying and using older drugs in new and innovative ways.”

In addition, Upkar plans to investigate how metabolic risk factors caused by other conditions could affect patients' outcomes. “I think integrating these factors will be key as our population continues to age,” he explains.

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