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New Hope for Liver Diseases
Date:5/23/2008

Scientists generate liver cells from embryonic stem cells, find clues to predict response to therapy

FRIDAY, May 23 (HealthDay News) -- Human liver cells have been generated from embryonic stem cells using a new model, hopefully opening the door to help scientists screen for harmful side effects of new drugs before they are used in patients.

That was one of several reports on advances against liver diseases that were presented this week at Digestive Disease Week 2008 in San Diego.

Other presentations involved ways to predict which patients with hepatitis C might benefit from long-term antibiotic therapy and information about how monitoring the body's viral load in hepatitis B patients may help predict liver cancer.

Scientists from the University of Edinburgh, Scotland, reported they had efficiently generated human liver cells from embryonic stem cells without the problems that have plagued scientists in the past. The new model is unique, said Dr. David Hay, a senior fellow at the university's MRC Centre for Regenerative Medicine, who spoke at a press conference Tuesday.

His team developed a model that allows them to focus on key enzymes which are crucial in drug metabolism. Other clinical applications, he said, include the fact that the liver cells generated in vitro could be used in bioartificial devices, helping maintain normal function when the liver fails.

Down the road, said another investigator, Dr. Philip Newsome, the hope is that the cells could be used in liver transplantation.

The advance was praised by the press conference moderator, Dr. John M. Vierling, chief of hepatology at Baylor College of Medicine, in Houston.

The team produced "highly differentiated cells that maintain function," Vierling said, a feat that has thus far proved elusive to others working on the effort. "It is an extraordinarily rich advance to be exploited in many ways," he added.

Predicting which patients with chronic hepatitis C infection, another liver ailment, will respond to treatment may be done by monitoring the dendritic cells, the cells that are the most potent stimulator of the immune system's T-cells, said Dr. John Mengshol, a fellow in the department of gastroenterology and hepatology at the University of Colorado Health Sciences Center, in Denver.

Treatment for hepatitis C virus routinely involves 48 weeks of combination antiviral therapy. Side effects include flu-like symptoms, and treatment is successful in only half of patients.

So, predicting who will and won't respond would be helpful. Mengshol and his colleagues evaluated 64 patients with hepatitis C virus of the genotype 1, the most common strain and the most difficult to treat.

Researchers have found that therapy affects the dendritic cells differently. Mengshol's team studied blood samples from each patient before treatment and at 24 weeks after starting it. They looked at the population of two different types of dendritic cells, among other factors.

Levels of one type of dendrite cells normalized in those who responded to the treatment, while levels of those who did not respond did not.

Why some patients respond to therapy and others don't has been an ongoing mystery, Mengshol said. Monitoring the dendritic cells may help doctors determine who might respond to therapy.

In another study, Dr. Uchenna Iloeje, director of virology for Global Clinical Research at Bristol-Myers Squibb Co., reported that monitoring the viral load of hepatitis B virus in patients with that disease is a significant predictor of who will be likely to get liver cancer.

In the study, researchers followed more than 3,500 patients for 11.5 years, Iloeje said.

"Over time, those at highest risk of liver disease had a sustained hepatitis B load," he said.

The liver is the largest organ inside the body. It changes food into energy, cleans alcohol and poisons from the blood, and makes bile, a liquid that aids digestion.

More information

For more on liver diseases, go to Medline Plus.



SOURCES: John M. Vierling, M.D., professor, medicine and surgery, chief, hepatology, Baylor College of Medicine, Houston; John Mengshol, M.D., Ph.D., fellow, University of Colorado School of Medicine, Denver; Uchenna Iloeje, M.P.H, M.B.B.S., director, virology, Global Clinical Research, Bristol-Myers Squibb; May 20, 2008, presentations, Digestive Disease Week 2008, San Diego


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