Use of clemizole compounds for treatment of inflammatory conditions

1. A method for treating lobular inflammation in a subject who has non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH), comprising:

administering to the subject an effective amount of clemizole, a deuterated analog of clemizole, or a clemizole metabolite.

2. The method of claim 1 , wherein the effective amount is 200-500 mg administered daily, twice daily, or thrice daily.

3. The method of claim 1 , wherein the clemizole, the deuterated analog of clemizole, or the clemizole metabolite is administered for greater than 2 months.

4. The method of claim 1 , wherein a result of the administering is reduction of inflammation, improved organ function, or reduced risk of development of disease or disease progression.

5. The method of claim 1 , wherein the administration is oral.

6. The method of claim 1 , wherein the administrating is intravenous.

7. The method of claim 1 , further comprising administering an effective amount of an inhibitor of CYP3A4.

8. The method of claim 7 , wherein the inhibitor of CYP3A4 is ritonavir or cobicistat.

9. The method of claim 1 , further comprising administering a second anti-inflammatory treatment.

10. The method of claim 9 , wherein the second anti-inflammatory treatment comprises: aspirin, ibuprofen, naproxen, corticosteroids, plumbagin, or immune selective anti-inflammatory derivatives.

11. The method of claim 1 , wherein the subject is administered the clemizole.

12. The method of claim 1 , wherein the lobular inflammation occurs in a subject with non-alcoholic steatohepatitis (NASH).

13. The method of claim 1 , wherein the lobular inflammation is characterized by an elevated plasma level of alanine aminotransferase in the plasma of the subject as compared to a level associated with a normal healthy control population.

14. The method of claim 1 , wherein the lobular inflammation in the subject is lobular inflammation characterized by a plurality of foci of infiltrating immune cells in a histological sample.

15. The method of claim 1 , wherein the lobular inflammation in the subject is diagnosed from examination of a sample obtained from a liver biopsy.

16. The method of claim 1 , wherein the lobular inflammation in the subject is diagnosed by ultrasound, computerized tomography, magnetic resonance imaging, a blood test, or NMR spectroscopy, including hyperpolarized 13 C-NMR spectroscopy.

17. The method of claim 1 , wherein the administering significantly reduces the subject's plasma level of alanine aminotransferase.

18. The method of claim 1 , further comprising administering an effective amount of an anti-NASH agent.

19. The method of claim 18 , wherein the anti-NASH agent is an FXR agonist, an LOXL2 inhibitor, a caspase protease inhibitor, cysteamine bitartrate, a galectin-3 inhibitor, a CCR2 and CCR5 pathway inhibitor, a cysteine depleting agent, a SGLT-2 inhibitor, GLP-1, bile acids, synthetic fatty acid and bile acid conjugates, a Sirtuin stimulant, an immunomodulator, or a PPAR agonist.

20. The method of claim 1 , further comprising treating the subject for insulin resistance by administering to the subject an effective amount of a medicament that increases insulin sensitivity in the subject.

21. The method of claim 20 , wherein the medicament that increases insulin sensitivity is metformin, thiazolidinedione, pioglitazone, or rosiglitazone.

22. The method of claim 1 , further comprising administering to the subject an effective amount of a medicament that decreases cholesterol and/or high triglycerides in the subject.

23. The method of claim 22 , wherein the medicament that decreases cholesterol and/or high triglycerides is a statin, a bile acid sequestrant, a cholesterol absorption inhibitor, a fibric acid derivative, or nicotinic acid.

24. The method of claim 12 , further comprising administering an effective amount of an inhibitor of CYP3A4.

25. The method of claim 24 , wherein the inhibitor of CYP3A4 is ritonavir or cobicistat.