Treatment of diseases associated with hepatic stellate cell activation using ammonia-lowering therapies

1. A method of treating or delaying the onset or progression of a disease associated with hepatic stellate cell (HSC) activation, comprising administering an ammonia-lowering agent to a subject in need thereof, wherein the ammonia-lowering agent comprises ornithine phenylacetate.

2. The method of claim 1 , wherein the administration is oral, intravenous, intraperitoneal, intragastric, or intravascular administration.

3. The method of claim 2 , wherein the administration is intravenous administration.

4. The method of claim 2 , wherein the administration is oral administration.

5. The method of claim 1 , wherein the disease associated with HSC activation is non-alcoholic fatty liver disease (NAFLD).

6. The method of claim 5 , wherein the NAFLD is non-alcoholic steatohepatitis (NASH).

7. The method of claim 5 , wherein the NAFLD is steatosis.

8. The method of claim 1 , wherein the disease associated with HSC activation is liver cancer.

9. The method of claim 1 , wherein the disease associated with HSC activation is a fibrotic condition.

10. The method of claim 9 , wherein the fibrotic condition is liver fibrosis.

11. A method of preventing non-alcoholic fatty liver disease (NAFLD), comprising administering an ammonia-lowering agent to a subject in need thereof.

12. The method of claim 11 , wherein the NAFLD is non-alcoholic steatohepatitis (NASH).

13. The method of claim 11 , wherein the NAFLD is steatosis.

14. The method of claim 11 , wherein the ammonia-lowering agent comprises a magnesium phosphate product (MGP), glycerol phenylbutyrate (GPB), sodium phenylacetate, sodium phenylbutyrate (NaPBA), glutamine, sodium benzoate,L-arabinose, a laxative, an antibiotic, ornithine in combination with at least one of phenylacetate and phenylbutyrate, or any combination thereof.

15. The method of claim 14 , wherein the ammonia-lowering agent comprises ornithine in combination with at least one of phenylacetate and phenylbutyrate.

16. The method of claim 15 , wherein separate pharmaceutically acceptable salts of the ornithine and at least one of phenylacetate and phenylbutyrate are administered to the subject.

17. The method of claim 16 , wherein at least one of phenylacetate and phenylbutyrate is administered as a sodium phenylacetate or sodium phenylbutyrate.

18. The method of claim 15 , wherein the ornithine is administered as a free monomeric amino acid or physiologically acceptable salt thereof.

19. The method of claim 15 , wherein the ornithine and phenylacetate is administered as ornithine phenylacetate.

20. The method of claim 11 , wherein the administration is oral, intravenous, intraperitoneal, intragastric, or intravascular administration.

21. The method of claim 20 , wherein the administration is intravenous administration.

22. The method of claim 20 , wherein the administration is oral administration.