A drug that reverses severe liver damage could be used to treat disease in heavy drinkers who find it impossible to give up alcohol. Scientists developed the drug after discovering a way to prevent the formation of excessive scar tissue caused by cirrhosis, hepatitis and other medical conditions.
To their surprise the drug not only slowed progression of the disease but also reversed damage to the organ.
The drug could have a profound impact on public health if it is proven to work in wider clinical trials. In Britain the rise in binge drinking has led to soaring rates of liver disease since the 1960s, with doctors warning cirrhosis is commonplace among men and women in their 20s and 30s.
Liver disease is the fifth largest killer in Britain, with cirrhosis alone claiming the lives of around 3,000 people each year. Worldwide the disease kills nearly 800,000 annually.
The liver is usually one of the body's most resilient organs and is the only one capable of regenerating after damage or injury. But excessive alcohol intake, hepatitis and damage from burns triggers the growth of fibrous scar tissue inside the liver which spreads and eventually destroys its ability to carry out crucial tasks such as combating infection and breaking down toxins.
Researchers led by Dr Martina Buck at the University of California, San Diego School of Medicine, found that damage to the liver, such as cirrhosis from heavy drinking, caused a specific group of cells known as hepatic stellate cells to go into overdrive and churn out large amounts of collagen, a tough connective tissue.
At normal levels collagen helps to heal wounds, but too much causes excessive scarring. The scientists then found that the cells only overproduced collagen in response to a chemical signal carried by a protein in the body called RSK. This signal, they realized, was critical to the progression of liver disease.
The scientists reasoned that if they could block the RSK signal they might be able to halt liver disease in its tracks.
To test the idea the scientists took two groups of mice and treated both with a toxin that is known to cause liver damage. One group was then given a drug called a peptide to block RSK while still receiving the toxin. The scientists found that while all of the mice in the untreated group developed severe liver disease, all of those given the drug had minimal or no liver disease.
Further investigation revealed that as well as blocking the formation of scar tissue in the liver, the drug was also killing off the overactive liver cells, allowing the organ to heal.
The drug is particularly promising, because biopsies from people with liver disease have revealed that RSK triggers liver cells to produce scar tissue in humans too. Cirrhosis can occur without any symptoms, but when they do appear they can include jaundice, a loss of appetite, nausea, itchy skin and tiredness.
Most hospitals will not perform liver transplants on heavy drinkers who show no intention of cutting down their alcohol intake. A drug could potentially protect a patient's liver while they have treatment to wean them off alcohol.
(China Daily January 1, 2008)
