Treatment of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis with delayed-release 6-mercaptopurine
Methods of treating patients suffering from non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), including those also suffering from type II diabetes mellitus (T2DM), with a delayed release pharmaceutical composition comprising 6-mercaptopurine are disclosed.
1. A method of treating a human patient suffering from nonalcoholic fatty liver disease (NAFLD), comprising periodically orally administering to the human patient a delayed release pharmaceutical composition comprising a pharmaceutically acceptable carrier and an amount of 6-mercaptopurine (6-MP) effective to treat the human patient, wherein the delayed release pharmaceutical composition administered to the human patient contains from about 1 mg to about 120 mg of 6-MP.
2. The method of claim 1 , wherein the NAFLD is simple steatosis.
3. The method of claim 1 , wherein the human patient is also suffering from type II diabetes mellitus (T2DM), type I diabetes mellitus (T1DM), pre-diabetes or insulin resistance or obesity, wherein obesity is defined as the patient having a body mass index of ≥30.
4. The method of claim 1 , wherein the patient has a NAFLD activity score of 0 or more.
5. The method of claim 1 , wherein the patient has evidence of liver fibrosis, inflammation or steatosis.
6. The method of claim 1 , wherein the patient does not have evidence of liver fibrosis.
7. The method of claim 5 , wherein the patient has a fibrosis score assessed by transient elastography of ≤F1.
8. The method of claim 1 , wherein the patient is male and has an alanine aminotransferase (ALT) level between 31 and 105 IU/L, inclusive; or wherein the patient is female and has an ALT level between 20 and 120 IU/L, inclusive.
9. The method of claim 1 , wherein the patient is also being administered thiazolidinediones (glitazones), a stable dose for 3 months of dipeptidyl peptidase 4 inhibitors (gliptins), or glucagon-like peptide-1 analogs or long acting insulin.
10. The method of claim 1 , wherein the patient is also being administered metformin and/or sulfonylureas or DDP4 and/or long acting insulin.
11. The method of claim 1 , wherein the patient is also being administered immune modulatory agents.
12. The method of claim 1 , wherein the delayed release pharmaceutical composition administered to the patient contains 40 mg to 120 mg of 6-MP.
13. The method of claim 1 , wherein the delayed release pharmaceutical composition is administered daily or twice a day.
14. The method of claim 1 , wherein the treatment results in an improvement in insulin resistance.
15. The method of claim 9 , wherein the patient is also being administered glucagon-like peptide-1 analogs.
16. The method of claim 1 , wherein said release of 6-MP occurs (a) at least 1 hour after passage of the pharmaceutical composition through the stomach or (b) about 5 to about 6 hours after ingestion of said pharmaceutical composition by the patient.
17. A method of treating a human patient suffering from nonalcoholic steatohepatitis (NASH), comprising periodically orally administering to the human patient a delayed release pharmaceutical composition comprising a pharmaceutically acceptable carrier and an amount of 6-MP effective to treat the human patient, wherein the delayed release pharmaceutical composition administered to the human patient contains from about 1 mg to about 120 mg of 6-MP.
18. The method of claim 7 , wherein the patient has a fibrosis score assessed by transient elastography.
19. The method of claim 17 , wherein said release of 6-MP occurs (a) at least 1 hour after passage of the pharmaceutical composition through the stomach or (b) about 5 to about 6 hours after ingestion of said pharmaceutical composition by the patient.