METHODS OF TREATING OR PREVENTING NONALCOHOLIC STEATOHEPATITIS AND/OR PRIMARY BILIARY CIRRHOSIS

1 . A method of treating or preventing non-alcoholic fatty liver disease (“NASH”) or primary biliary cirrhosis (“PBC”) in a subject, of inhibiting Novosphingobium aromaticivorans in a mammal, or of inhibiting Farnesoid X receptors (FXR) in a mammal, the method comprising administering orally to the subject or to the mammal ethyl eicosapentaenoate.

2 . The method of claim 1 , wherein the method comprises administering orally to the subject or mammal about 2 g to about 4 g per day of the ethyl eicosapentaenoate.

3 . The method of claim 1 , wherein the method comprises administering orally to the subject or mammal about 2 to about 4 capsules per day, each capsule comprising about 900 mg to about 1.1 g of ethyl eicosapentaenoate and not more than about 20% docosahexaenoic acid or its esters, by weight of all fatty acids present.

4 . The method of claim 1 , wherein prior to administration of ethyl eicosapentaenoate, the subject or mammal has one or more of: an elevated baseline alanine aminotransferase (“ALT”) level, an elevated baseline aspartate aminotransferase (“AST”) level, liver fibrosis, an elevated baseline gamma-glutanyl transferase level, an elevated baseline alkaline phosphatase level, an elevated baseline antimitochondrial antibody level, an elevated baseline antinuclear antibody level, an elevated total serum bilirubin level, and/or an elevated transaminase level.

5 . The method of claim 1 , wherein after administration of the ethyl eicosapentaenoate for a period of time, the subject or mammal has one or more of: a reduced alanine aminotransferase (“ALT”) level, a reduced aspartate aminotransferase (“AST”) level, reduced liver fibrosis, a reduced gamma-glutanyl transferase level, a reduced alkaline phosphatase level, a reduced antimitochondrial antibody level, a reduced antinuclear antibody level, a reduced total serum bilirubin level, and a reduced transaminase level compared to baseline, to a second subject who has not received ethyl eicosapentaenoate, or to placebo control.

6 . The method of claim 5 , wherein a triglyceride level, an IgM level, and/or a C-reactive protein level is reduced in the subject or mammal compared to baseline, compared to a second subject who has not received the ethyl eicosapentaenoate, or compared to placebo control.

7 . The method of claim 6 , wherein the subject or mammal exhibits one or more of: a reduction in an IgM level of at least about 0.5 g/L compared to baseline and a reduction in C-reactive protein of at least about 30% compared to baseline.

8 . The method of claim 1 , wherein the subject or mammal is administered the ethyl eicosapentaenoate daily for a period of at least 2 weeks.

9 . The method of claim 1 , wherein the ethyl eicosapentaenoate is administered in a pharmaceutical composition wherein the ethyl eicosapentaenoate comprises at least about 80% or at least about 90%, by weight, of all fatty acids present in the composition.

10 . The method of claim 9 , wherein the pharmaceutical composition comprises at least about 96%, by weight of all fatty acids present, ethyl eicosapentaenoate.

11 . The method of claim 10 , wherein the pharmaceutical composition comprises less than about 10%, by weight of all fatty acids present, docosahexaenoic acid or its esters.

12 . The method of claim 11 , wherein the pharmaceutical composition comprises less than about 3%, by weight of all fatty acids present, docosahexaenoic acid or its esters.

13 . The method of claim 12 , wherein the pharmaceutical composition comprises substantially no docosahexaenoic acid or its esters.

14 . The method of claim 1 , wherein the subject or mammal is not administered an additional NASH or primary biliary cirrhosis therapeutic agent.

15 . The method of claim 14 , wherein the additional NASH or primary biliary cirrhosis therapeutic agent is selected from the group consisting of:

L -alanine and pharmaceutically acceptable salts thereof;

obeticholic acid or a pharmaceutically acceptable salt, ester, glycine conjugate or taurine conjugate thereof;

ursodeoxycholic acid or a pharmaceutically acceptable derivative thereof;

23-N-carbacinnamyloxy-3α,7α-dihydroxy-5β-norcholanylamine;

a bile acid derivative of formula (I):

wherein R is H or alpha-hydroxy and the hydroxyl group at position 7 is in the alpha- or beta-position, or pharmaceutically acceptable salts, solvates or amino acid conjugates thereof;

a bile acid derivative of formula (II):

wherein R is ethyl, propyl or allyl;

a bile acid derivative of formula (III):

wherein R 1 is hydrogen, hydroxy, substituted or unsubstituted alkyl, or halogen; R 2 is hydrogen or α-hydroxy; R 3 is hydrogen, hydroxy, NH(CH 2 ) m SO 3 H, or NH(CH 2 ) n CO 2 H; R 4 is hydrogen, substituted or unsubstituted alkyl, or halogen; R 5 is unsubstituted or substituted alkyl, or aryl; R 6 is hydrogen, unsubstituted or substituted alkyl, or R 5 and R 6 taken together with the carbons to which they are attached form a ring of size 3, 4, 5, or 6 atoms; R 7 is hydrogen, substituted or unsubstituted alkyl, or hydroxy; R 8 is hydrogen, substituted or unsubstituted alkyl; R 9 is hydrogen, substituted or unsubstituted alkyl or taken together R 8 and R 9 form a carbonyl; R 10 is R 3 or SO 3 H; m is an integer 0, 1, 2, 3, 4, or 5; and n is an integer 0, 1, 2, 3, 4, or 5;

chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA), and/or the taurine and/or glycine conjugates thereof; and

organic or inorganic selenium, β-carotene and/or vitamin A.

16 . The method of claim 1 , wherein the subject or mammal is administered about 3.5 to about 4.5 g of ethyl eicosapentaenoate per day.

17 . The method of claim 3 , wherein the subject or mammal is administered about 4 capsules per day.

18 . The method of claim 1 , wherein the primary biliary cirrhosis is associated with Novosphingobium aromaticivorans bacterium.

19 . The method of claim 1 , wherein the subject or mammal consumes a Western diet.