A breakthrough in hepatitis treatment: targeting the liver, not the immune system

"Current treatments suppress the entire immune system, leaving patients vulnerable to infections," explains Zania. "We need therapies that target the liver more precisely, without affecting the rest of the body."

By uncovering how the liver controls immune responses, Zania’s research is paving the way for therapies that could reduce inflammation in autoimmune hepatitis and boost immune defences in viral hepatitis and liver cancer - all without the severe side effects of existing treatments.

The limits of existing treatments

Autoimmune and viral hepatitis are treated in very different ways, but both approaches have serious drawbacks.

For autoimmune hepatitis, patients are typically given immunosuppressants, such as steroids. These drugs help to reduce liver inflammation, but they also weaken the entire immune system, leaving patients more vulnerable to infections. "Steroids have significant adverse effects, including weight gain, bone thinning, and diabetes," explains Zania. "And for about one in five patients, these drugs don’t work at all."

For viral hepatitis, antiviral drugs can suppress the virus, but they rarely eliminate it completely. Hepatitis B, for example, is difficult to cure. "For hepatitis B, we desperately need treatments that can cure the infection, not just control it," says Zania. Hepatitis C, in contrast, can be cured with direct-acting antivirals, but these drugs are extremely expensive, limiting access to treatment globally. "If cost weren’t a barrier, we could eradicate hepatitis C from the face of the planet," Zania explains.

A major scientific discovery

Thanks to your support, Zania and her team have uncovered a completely new biological process in the liver, which they named enclysis.

Enclysis, from the Greek meaning "to enclose," describes how liver cells engulf regulatory T cells - a type of immune cell that normally helps keep inflammation under control.

"We used to think regulatory T cells died or moved away when their job was done," says Zania. "But our research shows that the liver plays an active role in determining their fate."

This discovery has major implications for treating liver disease. "We’ve discovered that enclysis plays a key role here,” says Zania. “Now, we want to find ways to either block or enhance this process - depending on the disease we are treating."

Testing new treatments

Zania’s team tested a large collection of existing medicines to see if any could influence enclysis - identifying several drugs that could either block or boost the process.

For autoimmune hepatitis, blocking enclysis could help preserve regulatory T cells, reducing liver inflammation while keeping the immune system intact.

Conversely, for viral hepatitis and liver cancer, boosting enclysis is useful. "On the flip side, boosting enclysis could enhance immune responses in the liver against infections and even cancer," says Zania.

With these early breakthroughs, Zania’s team has begun testing potential treatments in human liver tissue, working with Europe’s largest solid organ transplant centre in Birmingham. This approach ensures that any new treatment is developed with a direct path to benefiting patients.

A lasting legacy

Zania’s fellowship was funded in memory of Andrea Colville, who passed away from autoimmune hepatitis, leaving behind a young family.

"Knowing that my research was made possible by donations in Andrea’s memory has had a profound impact on me," says Zania. "Charitable funding accelerates discoveries that could change lives. It allows researchers to take bold steps into unexplored areas of science - leading to treatments that would not otherwise be possible."

This funding has also been pivotal in shaping Zania’s career. "This fellowship has been transformative - it allowed me to establish my own research team and pursue a high-risk project that could lead to new treatments for liver disease."

Thanks to your support, Zania’s team is making discoveries that could change the future of liver disease treatment - offering hope to those with hepatitis.

"These donations make a huge difference," says Zania. "Having the flexibility to explore new ideas, particularly in a high-risk field, is invaluable. This funding has been a lifeline."