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)