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8/16/2000

Possible Cirrhosis Therapy Discovered

Cheryl A. Thompson

Restoration of telomerase activity in hepatic cells could limit the development of liver cirrhosis or failure but also facilitate tumor formation, researchers suggested in the Feb. 18 issue of Science.

Telomerase maintains the integrity of telomeres—the protective endcaps on chromosomes. Working from another group’s discovery that the shortening of telomeres beyond a critical length causes hepatocytes to stop proliferating, Harvard Medical School researcher Ronald A. DePinho and colleagues studied genetically modified mice that did not produce telomerase. 

Without telomerase, telomere lengths and hepatocyte proliferation decreased in response to liver injuries. Restoration of telomerase activity by virus-assisted gene transfer before exposure to a hepatotoxin delayed the onset of ascites and development of liver fibrosis and steatosis—symptoms of liver cirrhosis in humans. 

Benefits from reactivating telomerase activity in human hepatocytes, the researchers cautioned, must be weighed against the potential formation of liver tumors. Other researchers have reported that more than 80 percent of hepatomas show evidence of telomerase activity. 

DePinho and colleagues suggested that the ideal candidate for telomerase therapy might be the patient with end-stage liver cirrhosis awaiting liver transplantation. Telomerase therapy could extend the survivable waiting time for a transplant, and then removal of the damaged organ should minimize the potential risk for cancer, they wrote.