Fibrosis is the accumulation of tough scar tissue; in the liver, it can impair function, eventually leading to liver failure. Liver fibrosis can occur in both chronic and acute liver diseases, including hepatitis, cirrhosis and cancer. The only effective treatment for fibrosis is to remove the underlying cause of the damage, which may not be possible in many cases of liver disease, leaving those affected with no effective therapies. But new results from rodent studies suggest that ghrelin, a naturally occurring gut hormone, has antifibrotic effects in the liver and may be a useful treatment for fibrosis in humans.

The studies were led by Ramón Bataller (Hospital Clínic, Barcelona, Spain) and reported in Hepatology (51, 974–985; 2010). First, the researchers assessed the effects of recombinant ghrelin in a rat model of chronic liver injury (induced by prolonged ligation of the bile duct). Treatment with ghrelin markedly reduced deposition of collagen and fibrosis (by ∼40%) and also reduced damage to liver cells. The group then tested recombinant ghrelin in a rat model of acute liver injury (induced by a single intraperitoneal injection of carbon tetrachloride). Rats that received ghrelin had significantly less liver-cell damage, inflammation and oxidative stress than did control rats. In a third set of experiments, Bataller and his colleagues investigated whether naturally occurring ghrelin had similar protective effects on the liver in mice. They induced chronic liver injury (by repeated injections of carbon tetrachloride) and then observed the fibrogenic responses in both wild-type and ghrelin-deficient mice. Ghrelin-deficient mice had more collagen deposition and liver damage than wild-type mice.

Taken together, the results indicate that ghrelin limits fibrosis and protects the liver from damage in rodents. Bataller's group further found that blood levels of ghrelin were lower in humans with chronic liver disease than in controls and, moreover, were lower in people with advanced fibrosis than in those with mild fibrosis. These findings suggest that ghrelin may regulate fibrogenesis in humans, making it a potentially valuable antifibrotic therapy for people with liver diseases.

Ghrelin is already known to have protective effects on various organs, including the pancreas, heart and gastrointestinal tract. It also has a role in regulating food intake. It has been tested in humans as a treatment for anorexia, caquexia and gastroparesis and, in those studies, had no major adverse effects. Further studies should evaluate the safety and efficacy of ghrelin as a treatment for liver disease.