A team of researchers from the University of Pittsburgh state that it might be possible to heal cirrhotic liver disease by rebooting the genes that control liver cell function. If validated in human studies, the game-changing strategy, described in an opensource study published in the Journal of Clinical Investigation, could potentially treat patients who are too sick for liver transplantation and, in the future, reduce the need for transplants.
The project grew out of the observation that not everyone who develops cirrhosis, or scarring of the liver, progresses to liver failure and its life threatening complications.
Even with the large amount of scar tissue that comes with cirrhosis, there should still be enough cells left to carry out the normal functions of the liver. So when the liver fails, it is the liver cells themselves that aren’t working properly. In this study, the team has demonstrated what has caused the problem, and more importantly, a way to repair it.
In the current study the researchers team developed a rat model of liver disease that mimics the form of human cirrhosis that progresses to organ failure. In previous work, they found that liver cells taken from animals with cirrhosis, but no liver failure, immediately functioned properly when transplanted into another animal. But cells transplanted from animals with both cirrhosis and liver failure did not function normally at first, indicating that both the liver cells and the liver tissue environment were damaged.
The researchers then compared the genes in the liver cells of the two groups of cirrhotic rats and found unusually low activity levels of the genes that control proteins which play a central role in liver cell function, the most important being a factor called HNF4. In the current study the team showed that restoring production of HNF4 by precision medicine reboots the liver cells to normal function. The team first showed this in lab tests and then in rats with liver failure.
The researchers noted that the animals got better almost immediately. Remarkably, the tests indicated that it wasn’t stem cells, regeneration or growth of new liver cells that caused improvement. Instead, the diseased cells had healed. It seems that in at least some forms of cirrhosis, chronic injury reprograms the liver cells to shut down HNF4 production, a dysfunction that eventually causes liver failure.
HNF4 precision medicine provided unique insight into the cause of liver failure and has significant potential for human therapy, but the investigators are now looking for other gene targets to develop simpler therapies, such as drugs that block the pathways that mediate failure. The team is now confirming their results with human liver cells.
Michelle Petersen is the founder of Healthinnovations, having worked in the health and science industry for over 21 years, which includes tenure within the NHS and Oxford University. Healthinnovations is a publication that has reported on, influenced, and researched current and future innovations in health for the past decade.
Michelle has been picked up as an expert writer for Informa publisher’s Clinical Trials community, as well as being listed as a blog source by the world’s leading medical journals, including the acclaimed Nature-Springer journal series.
Healthinnovations is currently indexed by the trusted Altmetric and PlumX metrics systems, respectively, as a blog source for published research globally. Healthinnovations is also featured in the world-renowned BioPortfolio, BioPortfolio.com, the life science, pharmaceutical and healthcare portal.
Most recently the Texas A&M University covered The Top 10 Healthinnovations series on their site with distinguished Professor Stephen Maren calling the inclusion of himself and his team on the list a reflection of “the hard work and dedication of my students and trainees”.
Michelle Petersen’s copy was used in the highly successful marketing campaign for the mega-hit film ‘Jumanji: The Next Level, starring Jack Black, Karen Gilian, Kevin Hart and Dwayne ‘The Rock’ Johnson. Michelle Petersen’s copywriting was part of the film’s coverage by the Republic TV network. Republic TV is the most-watched English language TV channel in India since its inception in 2017.
An avid campaigner in the fight against child sex abuse and trafficking, Michelle is a passionate humanist striving for a better quality of life for all humans by helping to provide traction for new technologies and techniques within healthcare.