Potential therapeutic strategy for fulminant hepatic failure

Mar 30 2009

Fulminant hepatic failure is a serious clinical disease and may threaten the life of patients. However, because of the damage of mass liver cells, the organ function is often irreversible due to the liver cell degeneration, swelling, or apoptosis.

Thus, to supply new sources of functional liver cells is a valuable choice for these patients.

A research team led by Dr. Yi -Jun Wang from Tianjin Medical University of China addressed this issue and their study will be published on March 28, 2009 in the World Journal of Gastroenterology .

In their study, HOC from rats were labeled with green fluocescent protein (GFP) or 5,6-carboxyfluorescein diacetate succinmidyl ester (CFDASE). Cell fluorescence was observed under fluorescent microscope at 6, 24, 48 and 72 h after labeling. CFDASE labeled HOC (5 × 106 cells each rat) were injected into livers of rats with FHF induced by D-galactosamine. Serum albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) levels were measured at different time points. Liver function of rats was examined on days 3, 7, 14 and 21 after HOC transplantation.

They found that the positive rate of GFP and CFDA-SE labeled HOC was 10% and 90%, respectively, with no significant change in cell viabilities. The survival rate was higher in HOC transplantation group than in control group, especially 48 (9/15 vs 6/15) and 72 h (9/15 vs 4/15) after HOC transplantation. The serum ALT, AST and TBil levels were decreased while the serum Alb level was increased after HOC transplantation. Fluorescence became faded and diffused in liver tissues, suggesting that proliferation and differentiation occur in transplanted HOC. The results of this study suggest that the presence of single nucleotide polymorphisms (SNPs) in certain positions had direct effect on the response of HCV patients to interferon therapy. Taking into consideration the positions of these mutations, different real-time PCR or other assays can be developed for detection of the SNPs to allow the prediction of the response to interferon therapy as a step for identification of patients who are more likely to respond to therapy.

Their result indicated that CFDA-SE is superior to GFP in labeling HOC, although fluorescence intensity is decreased progressively with cell division. HOC transplantation could improve the liver function and increase the survival rate of recipients.