Where to Begin?
When it comes to the subject of liver research, it’s hard to know where to begin as new advances are continuously evolving.
However, the biggest hurdle comes from the lack of funding from both Government and private enterprises. Far more money is needed if we
are going to resolve the unacceptably high death rate due to liver disease, which is increasing exponentially year on year.
The Gut
There are a number of studies presently looking at and understanding the role the gut plays in liver disease. The Roger
Willimans Institute of Hepatology at King’s College, London have been doing some remarkable work looking at the gut-
liver-brain axis in chronic liver disease.
The team is headed up be Prof Debbie Shawcross.
In this rather lengthy “The Inside Matters” podcast from 2022 (1hr 15min) Prof Debbie Shawcross talks with Dr James McIlroy about
Revolutionising Liver and Gut Health: The Future of FMT (faecal microbiota transplantation) and Diet.
I should point out to those who may be interested, that there are some further excellent podcasts available in this “The Inside Matters” series
which can be found here: https://insidematters.health/
More Guts “
Ammonia build-up kills liver cells but can be prevented using existing drugs”.
For those who have been reading about Hepatic Encephalopathy (HE) as mentioned in the “Ammonia” section, on page two (Wonderful World
of Astrocytes) you’ll know by now that the production of ammonia in the gut is a natural occurrence. But what has recently been discovered is
that high levels of ammonia kill liver cells by damaging the mitochondria that power the cells.
Of the 100 million people in the world with cirrhosis (scarring of the liver), about three million are hospitalised with an episode of confusion or
coma that is associated with elevated ammonia levels in blood and brain tissues, with 10-15% of these expected to die within three months of
the episode.
In promising news for these patients, the research demonstrated that an existing drug, called YAQ-005 (previously known as TAK-242), can
halt damage to the mitochondria in liver cells, allowing them to do their job of converting ammonia into urea so that it can be excreted as urine
(a process called the urea cycle).
Troels Jordansen, CEO of Yaqrit, added: “We are looking forward to advancing this innovative drug, licensed from UCL, into phase II trials in
acute-on-chronic liver failure. This is a complicated life-threatening condition and there is an urgent need for new approaches.”
A phase II clinical trial for YAQ-005, which will be sponsored by Yaqrit and funded by a European Union grant, is due to begin recruiting
patients with liver failure in mid-2025, which will provide the first proof of concept for this treatment in human patients.
More about this can be found here: https://www.ucl.ac.uk/news/2025/mar/ammonia-build-kills-liver-cells-can-be-prevented-using-existing-
drug
YAQRIT is a UCL spinout company dedicated specialising in interventions in liver disease, based on 20 years of research
and development at the University College London (UCL). There website can be found here: https://yaqrit.com/
Can Carbon beads help restore healthy gut microbiome and reduce liver disease progression?
The study has found that the carbon beads, licensed to UCL-spinout Yaqrit, were
effective in restoring gut health and had a positive impact on liver, kidney and brain
function in rats and mice. They were also found to be safe for human use.
The next step will be to see if the same benefits can be realised in humans, which
would pave the way for them to be used to treat diseases linked to poor gut health.
Worldwide, it is estimated that there are around 100 million people living with
cirrhosis of the liver and 10 million who have cirrhosis plus an additional complication.
Explaining the current clinical challenges, senior author Professor Rajiv Jalan from
the UCL Institute for Liver and Digestive Health, said: “The influence of the gut
microbiome on health is only just beginning to be fully appreciated. When the balance
of the microbiome is upset, ‘bad’ bacteria can proliferate and out-compete the ‘good’
bacteria that help keep the gut healthy.
“One of the ways they do this is by excreting endotoxin, toxic metabolites and
cytokines that transform the gut environment to make it more favourable to them and
hostile to good bacteria. These substances, particularly endotoxin, can trigger gut
inflammation and increase the leakiness of the gut wall, resulting in damage to other
organs such as the liver, kidneys and brain.
“In cirrhosis, a condition characterised by scarring of the liver, it is known that
inflammation caused by endotoxins can exacerbate liver damage. Part of the standard
treatment for cirrhosis is antibiotics aimed at controlling bad bacteria, but this comes
with the risk of antibiotic resistance and is only used in late-stage disease.”
To overcome this, scientists at UCL, in collaboration with Yaqrit, developed tiny oral
carbon beads, that have a special microscopic physical structure designed to adsorb
both large and small molecules in the gut.
In the study, researchers from UCL tested the effectiveness of the carbon beads, known by the product name CARBALIVE, to restore gut
health and assessed the impact on liver, kidney and brain function in rats and mice.
They found that when ingested every day for several weeks, the beads were effective in preventing the progress of liver scarring and injury in
animals with cirrhosis, and reduced mortality in animals with acute-on-chronic-liver-failure (ACLF).
The beads were also tested on 28 cirrhosis patients and proved to be safe with negligible side effects. If the same benefits observed in animal
models occur in humans, the beads could be an important new tool to help tackle liver disease.
Michal Kowalski, a Vice President and the CARBALIVE product lead at Yaqrit, said: “These novel, engineered carbon beads, which are
swallowed and pass through the body unaltered, are smaller than a grain of salt. They work by absorbing the endotoxins and other metabolites
produced by ‘bad’ bacteria in the gut, creating a better environment for the good bacteria to flourish and helping to restore microbiome health.
This prevents these toxins from leaching into other areas of the body and causing damage, as they do in cirrhosis.
“The results in animal models are very positive, with a reduction in gut permeability, liver injury, as well as brain and kidney dysfunction.”
The results open the door for further trials to test the efficacy of the carbon beads in humans, one of which is due to start soon. If the beads are
proven to be effective at halting or slowing the progression of liver damage, they could be an invaluable tool for treating liver disease and
possibly other conditions associated with poor microbiome health.
Professor Jalan, is a Professor of Hepatology at UCL and consultant at the Royal Free Hospital, added: “I have high hopes that the positive
impact of these carbon beads in animal models will be seen in humans, which is exciting not just for the treatment of liver disease but
potentially any health condition that is caused or exacerbated by a gut microbiome that doesn’t work as it should. This might include
conditions such as irritable bowel syndrome, for example, which is on the rise in many countries.
We are what we eat
I think there should be a more research and information readily available on the use of artificial sweeteners and colourings in our day-to-day lives.
If a person has stopped drinking alcohol, they will often go in search of a social substitute. Alcohol-free drinks, like Beer, wines and spirits are not
advisable. These are seen by healthcare professionals as signs that a person still has a yearning for the taste and wouldn’t be accepted if a person
were to later require an liver transplant. The risk of relapsing is considered too great. So, think about this possible scenario.
A 42-year-old man with end-stage liver disease who suffers from bouts of
Hepatic Encephalopathy and is also a type 2 diabetic due to his liver now being
insulin-resistant. He regularly drinks Diet Coke and Sainsbury’s Fiery Ginger
Beer (non-alcohol), as a substitute for alcohol. So, let's look at these two drinks.
Diet Coke
This product is seen as being one of the healthiest drinks available with four green traffic lights symbols.
Caramel E150d, also known as sulphite ammonia caramel, and is a food additive that can create a potentially carcinogenic residue when
processed with another ammonia-based colouring, E150c. The excerpt below has been taken from “The Royal Institution of Science” lecture
given by Dr Chris Van Tulleken back in 2023. The full lecture for those who are interested can be found here: https://youtu.be/KCCH0eP4nMQ
The other worrying factor is the use of artificial sweeteners. The Sainsbury’s Firey Ginger Beer contains Sucralose. It's also known by the brand
name Splenda. Sucralose is commonly used as a sugar substitute in both cooking and baking. It’s also added to thousands of food products
worldwide. It is said to be approximately 600 times sweeter than sugar.
But what of the side effects of eating/drinking too much Sucralose
• Leaky gut
Sucralose can cause bloating, diarrhoea, and gas. It can also damage the binding elements in intestinal cells, making the gut leaky. This can lead
to inflammatory bowel disease (IBD) and worsen chronic liver disease.
• Blood sugar levels
Sucralose can elevate blood sugar levels, which may increase the risk of type 2 diabetes, heart disease, and stroke.
• Immune system suppression
High doses of sucralose can suppress the immune system by lowering T-cell levels.
• Drug Effectiveness
Sucralose can reduce the absorption of certain therapeutic drugs, including those for cancer and heart disease.
• Inflammation
Sucralose can increase inflammation in the body, which can lead to problems like obesity and diabetes.
• Insulin resistance
Sucralose may cause increased insulin resistance.
• Intolerance
Symptoms of sucralose intolerance include:
Headaches
Mood changes
Dizziness
Hives
The severity of symptoms can vary widely among individuals and even between different types of artificial sweeteners. I think more advice is
certainly needed as many people will be led to believe that they are taking a sensible, healthy option when unbeknown to them, more damage
may be being done.
I think the golden rule here should be to check out all these sweeteners and colourings and use them sparingly.
More information can be found here at the British Heart Foundation website: https://www.bhf.org.uk/informationsupport/heart-matters-
magazine/news/behind-the-headlines/are-artificial-sweeteners-safe
