Cutting-edge science offers improved care for liver diseases

05/12/04

Risk factor identification, stem cell therapy targeted in new research

New Orleans, LA The liver is the largest organ in the human body, and proper functioning is critical for health and well being. Promising research in the identification, treatment and prevention of liver disease is being presented today at Digestive Disease Week in New Orleans. Digestive Disease Week (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.

"Liver disease is among the top 10 killers in the U.S.," said Anna Lok, M.D., of the University of Michigan. "The size of this population requires more attention from the research community for improved preventive and treatment solutions."

Transplantation of Human Umbilical Cord Blood Cells to Injured Liver (Abstract 101357*)

While stem cell transplantation continues to be controversial, research has shown significant clinical benefit for a variety of diseases. In this study, researchers from the Tokyo Medical and Dental University investigated the potential benefit of transplanting human umbilical cord blood cells (UCB) to repair damaged livers in recipient mice. UCB cells have many advantages as a source of stem cell transplantation because of the immaturity of newborn cells compared with adult cells.

To identify the benefit, the team collected UCB samples from full-term human deliveries (in Japan) with informed consent, and cultured the isolated cells with a combination of relevant growth/differentiation factors. UCB cells were transplanted into SCID mice carrying a gene modeling chronic liver injury. SCID mice are used to examine the effects and efficacy of transplants, because the mouse model does not reject engraftment (growth and development within the liver). In each model, the UCB cells were evaluated for engraftment and production of albumin (ALB, a protein indicating proper liver function) from three to 55 weeks after transplantation.

"What we found was that human umbilical cord blood cells may have the capacity to differentiate into functional liver cells after transplantation into humans," said Sei Kakinuma, M.D., Ph.D., lead author of the study. "These cells could be a potentially valuable source of cell transplantation, which could have an enormous positive effect on both acute and chronic liver injury therapy."

In the primary culture, about half of the UCB cells expressed ALB, and the hepatocyte-lineage markers were co-expressed in the ALB-positive cells in a 21-day culture. In addition, five to 10 percent of the ALB-expressing cells co-expressed cytokeratin-19, indicating that they were hepatic progenitor cells. In the transplantation model for chronic liver injury, inoculated UCB cells appeared at higher frequencies than the model for acute injury, and UCB-derived cells produced ALB in the recipient-mouse liver.

Gender, Race and Obesity Determine Differences in Children with Pediatric versus Adult-type NASH Histology (Abstract 105757*)

Potentially life-threatening non-alcoholic fatty liver disease (NAFLD) in obese children has distinct characteristics, often different from that found in adults, according to a University of California, San Diego (UCSD) School of Medicine study led by Dr. Jeffrey Schwimmer, assistant professor of pediatrics. The findings describe a new paradigm for diagnosis in this common condition found in obese children and offer the potential for improved care.

Between 1997 and 2003, the investigators identified 100 children ages two to 18 with biopsy-proven NAFLD. The investigators found clearly different patterns and locations of liver scarring and inflammation in children as compared to that typically seen in adults. They focused on the most severe form of NAFLD, called nonalcoholic steatohepatitis, or NASH, and divided it into two types; the adult pattern or Type 1, and the pediatric pattern or Type 2.

The researchers found that Type 2 NASH was more common than Type 1 NASH in children. Advanced liver scarring and cirrhosis were seen only in children with Type 2 NASH. In addition, they found that boys were more likely than girls to have Type 2 NASH and less likely to have Type 1. Type 2 NASH was also more common in children of non-white race or Hispanic ethnicity.

"We speculate that Type 2 NASH may also occur in adults and this needs to be looked for," said Jeffrey Schwimmer, M.D. "We also believe that the different injury pattern in children suggests differences in causation and, potentially, treatment and outcome."

Source: Eurekalert & others

Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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