Love Your Liver Month January 2022

January is Love Your Liver Month! Hosted by the British Liver Trust, the campaign is devoted to liver health awareness and helping people to understand how to keep their liver healthy. King’s College Hospital is at the forefront of liver research and treatment. To celebrate Love Your Liver month, we provide a snapshot of just some of the exciting research being done at the Trust with support from the NIHR/Wellcome King’s CRF that will help us and you to Love Your Liver!

Hepatitis B: a functional cure

King's College Hospital (KCH) is currently delivering and leading on multiple Phase 1 clinical trials that are testing drugs that provide different mechanisms to achieve a functional cure for hepatitis B. This is a viral infection that causes acute and chronic liver disease and, with 290 million people affected worldwide with a person dying from hepatitis B-related liver complications every 20 seconds, it represents a globally important pandemic.

While hepatitis B can be transmitted in many ways, such as through sexual intercourse or contact with infected blood, it is most commonly transmitted from mother to child during delivery. This usually results in chronic hepatitis B infection which can lead to debilitating and life-threatening conditions such as cirrhosis and liver cancer and represents the majority of illness and death associated with the disease.

Current treatments for chronic hepatitis B involve a range of antiviral therapies which stop the virus from replicating, yet this merely suppresses infection and many of these treatments have complications such as bone and kidney toxicity after long term treatment.

Dr Kosh Agarwal, KCH Consultant Hepatologist and NIHR CRN South London Clinical Director is currently leading a range of clinical trials that will lead to a functional cure for hepatitis. One such trial, a global study being led by KCH with support from the NIHR/Wellcome King’s CRF, will investigate the ability of small pieces of DNA – called oligonucleotides – to switch off essential machinery used by the hepatitis B virus to multiply in human liver cells. The first participant of many will be given the new drug on the 25th January and, if successful, this drug should prevent hepatitis B from growing in the liver and reduce viral load.

Dr Agarwal reflected:

“Given the success of hepatitis C drugs which means we now aim for elimination of this virus, our focus is now on a functional cure of hepatitis B with multiple new mode of action drugs. Given the rich ethnic diversity in south London, we have a higher prevalence of hepatitis B and it’s important we are able to offer clinical research to our local and regional population”.

Varices:

Prevention...

Dr Agarwal is also leading on clinical trials which aim to treat other drivers of liver disease. Non-Alcoholic Fatty Liver Disease, or NAFLD is mainly – but not always - caused by being overweight or obese and is estimated to affect around one in the three people in the UK. While early-stage NAFLD doesn’t usually cause symptoms or harm, it can progress to inflammation, damage and scarring of the liver. This advanced type of NAFLD is called Non-Alcoholic SteatoHepatitis (NASH) and, in turn, can lead to cirrhosis which can be fatal. Furthermore, a key complication of NASH is the development of swollen veins – also known as varices – in the oesophagus which develop due to pressure changes in the abdomen. If the varices rupture, the bleeding that ensues can be fatal.

Headed by Dr Agarwal and supported by the NIHR/Wellcome King’s CRF, the Liver Research team at KCH is leading a global Phase 2/3 clinical trial which will assess the safety and effectiveness of a new drug, belapectin, in preventing the formation of varices in NAFLD/NASH. The drug works by blocking the action of a molecular driver of fatty liver and fibrosis. Early reports have suggested that it may reduce blood pressure in vessels entering the liver and may in turn prevent the development of life-threatening varices.

...and treatment.

As well as preventing the formation of varices, researchers at KCH are finding ways to stop them from bleeding once they are formed, with the hope of saving lives.

The national BOPPP trial is an NIHR-funded Phase 4 clinical trial that is currently recruiting patients across over 40 NHS hospitals all over the UK, with KCH being the lead site. Led by KCH liver consultants Drs Vishal Patel and Mark McPhail and held at the NIHR/Wellcome King’s CRF, the trial aims to find out whether a widely-used beta blocker called carvedilol can prevent bleeding from these varices in patients with chronic liver disease.

Researchers will recruit 1,200 people from many different hospitals across the UK. Half of the people in the study will receive a placebo, or dummy drug, while the other half will receive carvedilol over the course of a three-year follow-up period. During that time, the research team will assess participants for any complications of cirrhosis (including bleeding) or side effects, as well as evaluating the cost-effectiveness of the drug.

The BOPPP trial also has an in-built sub-study called MBOP. Led by Dr McPhail, patients recruited to BOPPP can opt to provide annual blood, saliva and stool samples to help researchers to find out if carvedilol can prevent any other complications of liver disease or provide further insight into the drivers of liver disease, potentially uncovering novel therapeutic targets.

Of the study, Trial lead Dr Patel said:

“BOPPP is one of the largest portal hypertension studies to ever be conducted and will help to potentially guide clinical practice in the future to prevent complications in patients with cirrhosis at risk of bleeding”.

Dr McPhail added:

"This is an opportunity to define the therapeutic role and underlying mechanism of beta blockers in patients with cirrhosis".

Regular news and updates on the BOPPP and MBOP trials can can be found by following trial Twitter accounts @BOPPPtrial & @MBOPmechanistic.

Love your liver

While representing just a snapshot of liver research being undertaken at the Trust and the NIIHR/Wellcome King's CRF, these research stories show just three key ways in which our staff are working towards better liver care and even cures for significant liver diseases. In 2022, you too can Love Your Liver by sticking to a healthy diet, exercising regularly and moderating alcohol use while remaining aware of the symptoms of liver disease. Head to the British Liver Trust to find out more.