December 27, 2007
Nigel Hawkes, Health Editor
From Times Online

　Cirrhosis of the liver, an irreversible condition usually caused by heavy drinking, may be reversible
after all.

　Experiments in mice show that the condition may be prevented — and the liver allowed to recover —
if a protein activated by liver injury can be silenced.

　Experiments by the same scientists show that humans with damaged livers have the same protein,
which suggests that the findings could one day lead to a treatment.

　A team at the University of California in San Diego has shown that the excessive scarring in mouse
cirrhosis is caused by the activation of a protein called RSK. It produces large amounts of hepatic
stellate cells (HSCs) which create the collagen that forms the scars.

　It is the scarring, which occurs in response to liver injury, that causes permanent damage and
prevents the organ from regenerating.

　Dr Martina Buck and colleagues developed a small protein, or peptide, that blocked the creation
of RSK. Mice given a toxin that causes cirrhosis developed the condition, but those given the RSK-
blockers at the same time as the toxin did not develop it. The peptide also activated an “executioner”
protein which killed scarring cells but not normal cells.

　The mice continued to be given the liver-damaging toxin throughout the study. While the treated mice
began to recover, the condition of the control group worsened, the team reports in PLOS Online.

　Dr Buck said: “All control mice had severe liver fibrosis, while all mice that received the RSK-
inhibitory peptide had minimal or no liver fibrosis.

　“The HS cells continue to do their normal, healing work but their excess proliferation is controlled.
Remarkably, the death of HSCs may also allow recovery from liver injury and reversal of liver fibrosis.”

　Almost 800,000 people die from cirrhosis each year worldwide. The condition has a number of
causes, but alcoholism and infection by the hepatitis C virus are the most common. Currently there is
no treatment.

　Tissue samples taken from patients with liver disease were found to contain active RSK, while those
from healthy people did not, suggesting that the same model applies in humans.

　The research may have implications for many other conditions besides liver cirrhosis. Excessive
tissue scarring is also found in pulmonary fibrosis in the lungs, scleroderma — a chronic disease which
causes hardening of the skin — and burn injuries.