Methods for the treatment and prevention of liver disease
The presently disclosed invention is directed to the discovery that hepatocyte nuclear factor 4 alpha (HNF4α; also known as NR2A1), a transcription factor, reverses hepatocyte dysfunction in an animal model of cirrhosis, resulting in improvement in hepatic function, treatment of cirrhosis, and prolonged survival.
1. A method of treating hepatic failure in a human subject, comprising administering intravenously, to a human subject having liver failure, a therapeutically effective amount of a pharmaceutical composition comprising a therapeutic adeno-associated virus vector comprising a nucleic acid encoding a human HNF4α, protein operably linked to a promoter, wherein administration of said nucleic acid results in expression of the human HNF4α protein and improved liver function.
2. The method of claim 1 , wherein the improved liver function is indicated by an increase in serum albumin.
3. The method of claim 1 , wherein the improved liver function is indicated by decreased serum ammonia level.
4. The method of claim 1 , wherein the improved liver function is indicated by a decrease in total bilirubin.
5. The method of claim 1 , wherein the improved liver function is indicated by an improved encephalopathy score.
6. The method of claim 1 , wherein the administration of said nucleic acid treats Child-Pugh Class B or C.