Treatment of fibrosis using FXR ligands
The present invention relates to a method for inhibiting fibrosis that occurs in an organ where the farnesoid X receptor (FXR) is expressed. This method involves the step of administering a high potency, activating ligand of FXR in an effective amount to a patient who is not suffering from a cholestatic condition. The invention also provides pharmaceutical compositions containing an effective amount of an FXR ligand and kits for dispensing the pharmaceutical compositions.
1. A method of treating liver fibrosis in a human not suffering from a cholestatic condition, comprising the steps of selecting a human who is not suffering from a cholestatic condition and administering to the human 6-ethyl-chenodeoxycholic acid at a daily dose of 5-500 mg orally.
2. The method of claim 1 , wherein the cholestatic condition is defined as having abnormally elevated serum levels of alkaline phosphatase, γ-glutamyl transpeptidase (GGT), and 5′ nucleotidase.
3. The method of claim 2 , wherein the cholestatic condition is further defined as presenting with at least one clinical symptom.
4. The method of claim 3 , wherein the symptom is itching (pruritus).
5. The method of claim 1 , wherein the cholestatic condition is selected from the group consisting of primary biliary cirrhosis, primary sclerosing cholangitis, drug-induced cholestasis, hereditary cholestasis, and intrahepatic cholestasis of pregnancy.
6. The method of claim 1 , wherein the human is not suffering from a cholestatic condition associated with a disease or condition selected from the group consisting of primary liver and biliary cancer, metastatic cancer, sepsis, chronic total parenteral nutrition, cystic fibrosis, and granulomatous liver disease.
7. The method of claim 1 , wherein the human has liver fibrosis associated with a disease selected from the group consisting of hepatitis B; hepatitis C; parasitic liver diseases; post-transplant bacterial, viral and fungal infections; alcoholic liver disease (ALD); non-alcoholic fatty liver disease (NAFLD); non-alcoholic steatohepatitis (NASH); liver diseases induced by methotrexate, isoniazid, oxyphenistatin, methyldopa, chlorpromazine, tolbutamide, or amiodarone; autoimmune hepatitis; sarcoidosis; Wilson's disease; hemochromatosis; Gaucher's disease; types III, IV, VI, IX and X glycogen storage diseases; α 1 -antitrypsin deficiency; Zellweger syndrome; tyrosinemia; fructosemia; galactosemia; vascular derangement associated with Budd-Chiari syndrome, veno-occlusive disease, or portal vein thrombosis; and congenital hepatic fibrosis.
8. A method of treating non-alcoholic steatohepatitis in a human not suffering from a cholestatic condition, comprising the steps of selecting a human who is not suffering from a cholestatic condition and administering to the human 6-ethyl-chenodeoxycholic acid at a daily dose of 5-500 mg orally.