Efficacy and Safety of Oltipraz in the Patients With Non-alcoholic Fatty Liver Disease

• change in ALT, AST and total bilirubin [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• change in Cholesterol, Triglyceride [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• change in HOMA-IR [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• change in BMI [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• changes in NAS [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Subjects with liver biopsy:

Dithiolethiones, a novel class of adenosine monophosphate-activated protein kinase (AMPK) activators, prevent insulin resistance through AMPK-dependent p70 ribosomal S6 kinase-1 (S6K1) inhibition. And it is well known that the modulation of S6K1 by oltipraz inhibited the development of insulin resistance and hyperglycemia through the AMPK-S6K1 pathway.Also some research reported that LXRg (a member of the nuclear hormone receptor)-mediated increases in SREBP-1c (the sterol regulatory element-binding protein-1c gene) promote the expression of lipogenic genes and enhance fatty acid synthesis and oltipraz inhibits LXRg and SREBP-c. Therefore, Oltipraz inhibits fatty acid synthesis through AMPK-S6K1 pathway and LXRg-SREBP-1c pathway in liver.

• Drug: Placebo
  30mig/bid or 60mg/bid P.O
• Drug: Oltipraz
  30mig/bid or 60mg/bid P.O

• Placebo Comparator: Placebo
  Intervention: Drug: Placebo
• Experimental: Oltipraz
  Intervention: Drug: Oltipraz

Inclusion Criteria:

• Patients over 18, under 75 years of age
• Patients with non-alcoholic fatty liver disease

Exclusion Criteria:

• Over 2 ratio of AST to ALT
• Type 1 diabetes mellitus (insulin-dependent diabetes mellitus)
• Disorder in liver function with an exception of non-alcoholic fatty liver (e.g. Virus infection, biliary atresia, autoimmune hepatitis and etc.)
• Patients who have been taken drugs induced fatty liver for over 3 month within 1 year of participation in this study; amiodarone, tamoxifen, methotrexate, tetracyclines, glucocorticoids, anabolic steroids, over usual dose of estrogen for hormone replacement therapy and valproate
• Patients who has been taken any medications that could affect the treatment for non-alcoholic steatohepatitis: insulin, insulin sensitizer(metformin, thiazolidinedione), high dose of vitamin E, high dose of UDCA, pentoxifylline, SAM-e, Betaine, types of Statin, types of fibrate and orlistat
• Patients who had a Bariatric surgery less than 6 month prior to the participation in the study
• Patients who are judged by investigator that participation of the study is difficult due to disease as follow; hepatic cirrhosis, Wilson's disease, malignant tumor, serious metabolic disease, severe renal disease, severe pulmonary disease, severe cardiovascular disease, severe nervous disease/psychiatric disorder, muscle disease and etc
• Any history of immune disorder which affect the changes in cytokine:

inflammatory bowel disease, autoimmune thrombocytopenic purpura, system lupus erythematosus, autoimmune hemolytic anemia, severe psoriasis, rheumatic arthritis and etc

• Patients who have received treatment that may affect liver function within 1 month prior to the participation in the study
• Patient who has been administered other investigational product within 1 month prior to the participation in the study
• Patient who is not allowed to get MRS test: pacemaker, shunt and etc
• Pregnant or nursing women
• Patient who considered ineligible for participation in the study as Investigator's judgment