The liver is known for its ability to regenerate (see last issue’s cover story for more information). It can completely regrow itself even after two-thirds of its mass has been surgically removed. But damage from medications, alcohol abuse or obesity can eventually cause the liver to fail. Currently, the only effective treatment for end-stage liver disease is transplantation.
However, there is a dearth of organs available for transplantation. Patients may have to wait from 30 days to over five years to receive a liver for transplant in the U.S. Of the over 11,600 patients on the waiting list to receive a liver transplant in 2021, only a little over 9,200 received one.
But what if, instead of liver transplantation, there was a drug that could help the liver regenerate itself?
I am the founding director of the Pittsburgh Liver Research Center and run a lab studying liver regeneration and cancer. In our recently published research, my team and I found that activating a particular protein with a new medication can help accelerate regeneration and repair after severe liver injury or partial surgical removal in mice.
The liver performs over 500 key functions in your body, including producing proteins that carry fat through the body, converting excess glucose into glycogen for storage and breaking down toxins like ammonia, among others.
Liver cells, or hepatocytes, take on these many tasks by a divide-and-conquer strategy, also called zonation. This separates the liver into three zones with different tasks, and cells are directed to perform specialized functions by turning on specific genes active in each zone. However, exactly what controls the expression of these genes has been poorly understood.
Over the past two decades, my team and other labs have identified one group of 19 proteins called Wnts that play an important role in controlling liver function and regeneration. While researchers know that Wnt proteins help activate the repair process in damaged liver cells, which ones actually control zonation and regeneration, as well as their exact location in the liver, have been a mystery.
To identify these proteins and where they came from, my team and I used a new technology called molecular cartography to identify how strongly and where 100 liver function genes are active. We found that only two of 19 Wnt genes, Wnt2 and Wnt9b, were functionally present in the liver. We also found that Wnt2 and Wnt9b were located in the endothelial cells lining the blood vessels in zone 3 of the liver, an area that plays a role in a number of metabolic functions.
Eliminating the two Wnt genes from endothelial cells also completely stopped liver cell division, and thus regeneration…
To our surprise, eliminating these two Wnt genes resulted in all liver cells expressing only genes typically limited to zone 1, significantly limiting the liver’s overall function. This finding suggests that liver cells experience an ongoing push and pull in gene activation that can modify their functions, and Wnt is the master regulator of this process.
Eliminating the two Wnt genes from endothelial cells also completely stopped liver cell division, and thus regeneration, after partial surgical removal of the liver.
We then decided to test whether a new drug could help recover liver zonation and regeneration. This drug, an antibody called FL6.13, shares similar functions with Wnt proteins, including activating liver regeneration.
Over the course of two days, we gave this drug to mice that were genetically engineered to lack Wnt2 and Wnt9b in their liver endothelial cells. We found that the drug was able to nearly completely recover liver cell division and repair functions. Lastly, we wanted to test how well this drug worked to repair the liver after paracetamol overdose.
Paracetamol, or acetaminophen, is an over-the- counter medication commonly used to treat fever and pain. However, an overdose of paracetamol can cause severe liver damage. Without immediate medical attention, it can lead to liver failure and death. Paracetamol poisoning is one of the most common causes of severe liver injury requiring liver transplantation in the U.S. Despite this, there is currently only one medication available to treat it, and it is only able to prevent liver damage if taken shortly after overdose.
…one dose was able to decrease liver injury biomarkers … in the blood and reduce liver tissue death.
We tested our new drug on mice with liver damage from toxic doses of paracetamol. We found that one dose was able to decrease liver injury biomarkers—proteins the liver releases when injured— in the blood and reduce liver tissue death. These findings indicate that liver cell repair and tissue regeneration are occurring.
One way to address liver transplantation shortages is to improve treatments for liver diseases. While current medications can effectively cure hepatitis C, a viral infection that causes liver inflammation, other liver diseases haven’t seen the same progress.
Because very few effective treatments are available for illnesses like nonalcoholic fatty liver disease and alcoholic liver disease, many patients worsen and end up needing a liver transplant.
My team and I believe that improving the liver’s ability to repair itself could help circumvent the need for transplantation. Further study of drugs that promote liver regeneration may help curb the burden of liver disease worldwide.
– Satdarshan (Paul) Singh Monga, Professor of Pathology and Medicine, University of Pittsburgh
This article is republished from The Conversation under a Creative Commons license. Read the original article.
]]>The Guide, available for viewing and downloading at liverwell.org.au, promotes steps that Aboriginal people can take to look after the health of their liver and promote healthy activity, food and drink in their family and community.
There are higher rates of liver disease in Aboriginal communities and it is getting worse. Aboriginal and Torres Strait Islander people are 10 times as likely to be diagnosed with viral hepatitis as non-Aboriginal populations.
Melanie Eagle, LiverWELL CEO, was excited to have the guide available in time for NAIDOC week. “LiverWELL is committed to offering specially designed tools to assist the community to take control of their health and counteract the disproportionate impact of liver disease. We hope that the community will find this a useful resource, and we envisage it evolving over time with further contributions and stories from community members.”
Though designed and published in Victoria, the information in the guide is general enough to be useful for Indigenous Australians everywhere, including in South Australia. Designed by Aboriginal graphic designer Sean Miller, it features a number of exciting Indigenous art pieces to add to its appeal. It is endorsed by Creative Director of the ILBIJERRI Theatre Company, Kamarra Bell-Wykes, who is a strong advocate for good liver health in Aboriginal communities, with whom Hepatitis SA has a strong relationship. Her advice? “Love your liver! Love your life! Love yourself!”
]]>It’s the time of year when articles about the magical benefits of detoxing flood the media. A fresh start is always appealing, especially when you’ve over-indulged. Unfortunately, detoxing—the idea that you can flush away stored toxins from bad food, alcohol or drugs—is a myth; our bodies simply don’t work this way.
To begin with, these toxins aren’t stored in our bodies. Luckily for us, our liver, kidneys, lungs and skin are breaking down and removing them all of the time. Nothing we do can make this system work better, aside from being healthier. (See medical researcher Nick Fuller’s article: Science or Snake Oil: can a detox actually cleanse your liver? )
… some detox products even contain ingredients that could be harmful for your liver. This is especially worrying for people with … liver disease.
Sadly, quick-fix detox is a big business and this multi-billion dollar industry takes advantage of the fact that their products are unregulated. Manufacturers try to lure us in with promises of renewed energy, glowing skin and healthier livers. The truth is that not only can’t they prove these miraculous results but some detox products even contain ingredients that could be harmful for your liver. This is especially worrying for people with viral hepatitis or liver disease.
Strict diets and juice fasts are also promoted as a way to detox but these won’t affect how quickly your body deals with toxins either. Depending on the diet you may feel better or worse, it’s anybody’s guess.
In contrast, looking after yourself properly has real benefits that can’t be matched by a mythical detox. Here are our top tips for feeling better this year.
Fresh fruit and vegetables, good carbohydrates, good fats, lean sources of protein and low-fat dairy (or substitutes) are all high on the list of foods that are good for you and make you feel good. While the occasional treat is good for your mood, living on a regular diet of junk-food is not. Our Eat Well For Your Liver resource has more information and recipes.
Our liver has a clock and needs a good block of sleep at night to perform some of its most important functions. Aim for 7-8 hours most nights. See our post on sleep for some tips if this is hard for you. See Working with your liver’s clock to learn more about your liver’s cycle.
We all have different capabilities but some form of exercise is beneficial for most people, most of the time. Low intensity, unfocussed exercise such as a stroll or roll around the park can really lift your mood. Regular, moderate exercise can improve fitness, wellbeing and quality of life. Think about what is possible and enjoyable for you and aim to do a bit more than you do now, building up over time.
People with viral hepatitis or liver disease need to be especially careful about the amount of alcohol they drink. If you want to drink it’s best to discuss it with your doctor or specialist so you know what’s right for you. Drinking more than your liver can handle can make you feel bad now and damage your liver in the long term.
Not only does smoking increase the risk of developing liver cancer for people with viral hepatitis, smoking makes you feel bad, mentally and physically. If you still smoke quitting can make a real difference to your health and how well you feel day to day. The Quitline can help – 13 78 48
Most importantly, if you have viral hepatitis or other liver disease, make sure you are getting the proper medical attention.
You can’t control all aspects of how viral hepatitis makes you feel but if you haven’t been getting the care you need, be sure to visit your doctor or contact the viral hepatitis nurses. People with hepatitis C can now be treated with an over 95% success rate and new hepatitis B treatments are managing the condition better than ever before. If you have hepatitis B or other liver diseases regular monitoring is vital to maintaining your health and helping you feel better.
Call our Helpline on 1800 437 222 for more information. Click here for a list of South Australian liver clinics.
Further reading on the detox myth
https://theconversation.com/do-you-really-need-a-detox-52077
https://www.theguardian.com/lifeandstyle/2014/dec/05/detox-myth-health-diet-science-ignorance
https://www.sbs.com.au/food/article/2018/01/11/no-detoxing-isnt-actually-thing