Fibrosis Can Be Reversed and Cured

A new discovery could lead to the first cure for cirrhosis of the liver.

San Diego researchers have proven liver fibrosis can be stopped and reversed in mice. This could help scientists develop new treatments and cures for conditions that cause excessive scarring such as viral hepatitis, fatty liver disease, cirrhosis, pulmonary fibrosis, scleroderma, and burns.

Previous research from the University of California, San Diego found the cause of the excess fibrous growth that leads to liver fibrosis and cirrhosis and developed a way to block it in mice. Now the researchers show that by blocking a protein linked to overproduction of scar tissue they can stop fibrosis from progressing in mice as well as reverse some of the cell damage already done.

In conditions such as cirrhosis, oxidative stress activates hepatic stellate cell (HSC) which results in a lot of collagen. Collagen is necessary to heal wounds but too much of it causes scar tissue. The study shows activating a protein called RSK triggers HSC and is critical for liver fibrosis to progress. Researchers developed an RSK inhibitory peptide to block the activation of RSK.

When scientists gave mice the RSK-inhibitory peptide it stopped RSK activation which kept the HSC from growing, blocking the excessive collagen response. The peptide also killed the cells producing liver cirrhosis but did not harm the normal cells.

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

The study found similar results in humans with severe liver fibrosis but not in control livers which suggests the pathway is also relevant in human liver fibrosis.

SOURCE: PLoS, published online Dec. 26, 2007