Behind the Headlines - 'Friendly' virus repairs damaged liver cells (but only in mice)

Behind the Headlines
What is Behind the Headlines?
Each day the NHS Choices team selects health stories that are making headlines. These, along with the scientific articles behind the stories, are sent to Bazian, a leading provider of evidence-based healthcare information. Bazian's clinicians and scientists analyse the research and produce impartial evidence-based assessments, which are edited and published by NHS Choices.

'Friendly' virus repairs damaged liver cells (but only in mice)

Friday June 3 2016

There are more than 100 different types of liver disease

"Have scientists found a cure for alcoholism?," the Mail Online asks, missing the point of the research entirely.

Researchers were able to improve liver damage in mice, but this does not amount to curing an addiction to alcohol.

The study showed it was possible to create "bespoke friendly" viruses to infect cells known as myofibroblasts, which are cells associated with tissue repair. The virus passed on instructions that transformed the myofibroblasts into healthy liver cells in mice who had fibrosis (scarring) of the liver, known as cirrhosis.

Not all the experiments in the mice worked, but in those that did, the transformed liver cells looked and behaved normally, replaced some of the diseased liver cells, and led to less liver scarring.

Researchers will now attempt to refine this technique before seeing if it works in humans.

Right now, this technique is not available as a new treatment. It represents one of the earliest stages of treatment discovery and development, which can take decades from start to finish.

If you do have a lifestyle that increases your risk of liver disease, such as heavy alcohol consumption, being obese, or injecting drugs, you should ask your GP for a liver function test. The symptoms of liver disease often only occur once it is too late to undo the damage.

Taking action to reduce your risk before this happens could restore your liver back to good health.

Where did the story come from?
The study was carried out by researchers from The University of California and funded by grants from the US National Institutes of Health.

The study was published in the peer-reviewed science journal Cell – Stem Cell.

The Mail Online's reporting was poor, failing on three main points.

Firstly, it asked an inappropriate question in its headline – "Have scientists found a cure for alcoholism?". A cure, or at least a partial repair, of liver damage would not amount to a cure for alcohol addiction. The headline confused alcohol with its main health consequence – alcoholic liver disease. There are many other consequences of chronic alcohol misuse – be it social, financial or mental health-related.

Secondly, nowhere in the article (let alone in the headline) did it mention that the study was on mice, so readers might naturally assume it involved people.

Thirdly, there are other causes of liver disease aside from alcohol, such as obesity (non-alcoholic fatty liver disease) or infection with the hepatitis C virus. The mice studied didn't have alcohol-induced liver disease.

What kind of research was this?
This was a laboratory study investigating a potential new treatment approach for liver fibrosis.

Liver fibrosis is the scarring and demise of your liver, following repeated cell damage and inflammation. Fibrosis can have many causes, including viruses (like hepatitis B and C), alcohol misuse, and fatty liver disease.

Despite the liver's somewhat unique ability to recover and regenerate, when liver cells are repeatedly damaged, such as through sustained heavy alcohol use, they gradually die and the organ stops working. Part of the damage is the build-up of collagen, which causes scarring and restricts blood flow.

The poorly functioning liver and restricted blood flow causes symptoms including jaundice, weight loss, swelling of the abdomen, vomiting blood and, ultimately, death.

The only cure for severe liver scarring, where the liver loses most of its functioning ability (liver failure), is a liver transplant. But there are not enough organs to meet demand, so medical researchers are always looking for alternatives.

What did the research involve?
The researchers reprogrammed types of cells called myofibroblasts into liver cells by injecting reprogramming instructions, via a "designer virus", into mice with liver disease.

Myofibroblasts were chosen as the target, as they produce the excess collagen which causes scarring.

The researchers carefully analysed whether the reprogrammed cells behaved like normal liver cells in the lab and had similar DNA and protein profiles. They also tested whether once injected they were able to grow, repair and replace some or all of the liver damage.

Part of the challenge was devising a safe and effective way to deliver the reprogramming instructions to the mice myofibroblast cells. They used adeno-associated virus 6 (AAV6) vectors to act as delivery vehicles.

This involved taking the packaging of a virus and modifying it, so instead of infecting a mouse and causing disease, it infects the mouse and makes the modifications they wanted – in this case, turning myofibroblasts into liver cells. This involves replacing and modifying the virus DNA – that instructs the virus cell – with DNA encoding instructions you want.

What were the basic results?
The researchers overcame the delivery and reprogramming challenges to influence some cells to change from myofibroblasts into liver cells by injecting the reprogramming instructions into the bloodstreams of the mice using different AAV vectors.

Not all of the vectors worked. But in those that did, not only did some cells change, they appeared to function like normal liver cells, were able to grow and multiply, and reduced the amount of problematic collagen.

This partially alleviated two of the main causes of liver fibrosis – liver cell death and collagen build up – in mice with liver disease.

How did the researchers interpret the results?
The researchers concluded: "Our study establishes the feasibility of in vivo reprogramming of myofibroblasts into fully functional hepatocytes [liver cells] using AAV vectors, a gene delivery tool that proved to be safe and effective in clinical trials of liver-directed gene therapy".

Conclusion
This study showed it was possible to engineer and inject instructions that transform myofibroblasts into liver cells in mice with liver disease, which is quite a feat. Not all delivery mechanisms, called vectors, worked, but in those that did, the new liver cells looked normal, replaced some of the dying cells, and led to less damage due to collagen build up.

Despite the alcoholism-related headline, the mice did not have alcohol-induced liver damage – although this is a major cause of liver damage in people.

This study serves to prove this approach is feasible, and was successful in doing this. Researchers will now need to refine the technique before testing to see if it works in human trials.

The good news is the vector delivery system has been used in human trials before – although not containing the same liver cell transformation message – so has a better chance than normal of working in people.

Right now this technique is not available as a new treatment. It represents one of the earliest types of treatment development, which can take decades from start to finish.

Currently the only cure for severe liver scarring is an organ transplant, but many die while waiting for a transplant as need far outstrips supply. If you are not on the register, you could save lives by joining the NHS Organ Donor Register today.

The liver is tough and can regenerate itself, but it can only take so much damage. Moderating your alcohol consumption, maintaining a healthy weight, and reducing your risk of contracting hepatitis C (mainly spread by injecting drugs), will do much to keep your liver healthy.

Analysis by Bazian. Edited by NHS Choices. Follow NHS Choices on Twitter. Join the Healthy Evidence forum.