Methods of treating fibrotic liver diseases or conditions with indeglitazar
The present invention relates to methods of treating alcoholic hepatitis in a subject, comprising administering to the subject a therapeutically effective amount of indeglitazar or a pharmaceutically acceptable salt thereof.
1. A method of treating alcoholic hepatitis in a subject, comprising administering to the subject a therapeutically effective amount of indeglitazar or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the treatment results in an improvement in a fibrosis marker selected from TIMP-1, TIMP-2, hyaluronic acid, P3NP, NFS, FIB-4 score, ELF score, Pro-C3, and combinations thereof.
3. The method of claim 1 , wherein the treatment results in a reduction of alanine aminotransferase (ALT) activity in liver of at least 50%.
4. The method of claim 1 , wherein the treatment results in a reduction of the fibrosis marker hepatic hydroxyproline of at least 25%.
5. The method of claim 1 , wherein the treatment results in a reduction in the marker bilirubin of at least 15%.
6. The method of claim 1 , wherein the treatment results in a reduction in plasma TGF-β1 of at least 25%.
7. The method of claim 1 , wherein the treatment results in a reduction in plasma TNF-α of at least 25%.
8. The method of claim 1 , wherein the treatment results in a reduction of liver triglycerides of at least 15%.
9. The method of claim 1 , wherein the treatment results in an increase in plasma adiponectin of at least 100%.
10. The method of claim 1 , wherein the treatment results in a reduction of alanine aminotransferase (AST) activity in liver of at least 50%.
11. The method of claim 1 , wherein the subject does not have type 2 diabetes.
12. The method of claim 1 , wherein hepatocellular karyomegaly is reduced in the subject following treatment.
13. The method of claim 1 , wherein hepatocyte ballooning is reduced in the subject following treatment.
14. The method of claim 1 , wherein the treatment results in an improvement in levels of fibrinogen, hsCRP, alpha2 macroglobulin, haptoglobin, or a combination thereof.
15. The method of claim 1 , wherein the subject has a BMI greater than 30.
16. The method of claim 1 , wherein the subject has an F1 grade of fibrosis.
17. The method of claim 1 , wherein the therapeutically effective amount of indeglitazar comprises about 50 mg/day or about 100 mg/day.
18. The method of claim 1 , wherein indeglitazar is administered orally.
19. The method of claim 1 , wherein the subject is administered one or more additional therapeutically active agents.
20. The method of claim 19 , wherein the one or more additional therapeutically active agents is selected from prednisolone, pentoxifylline, and a combination thereof.
21. The method of claim 1 , wherein the method results in an improvement in NASH CRN fibrosis score.
22. The method of claim 1 , further comprising administering an effective amount of resmetirom to the subject.