Original Article—Liver, Pancreas, and Biliary Tract

Journal of Gastroenterology

, Volume 46, Issue 1, pp 101-107

Efficacy of long-term ezetimibe therapy in patients with nonalcoholic fatty liver disease

  • Hyohun ParkAffiliated withDepartment of Gastroenterology and Hepatology, Saiseikai Suita HospitalDepartment of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
  • , Toshihide ShimaAffiliated withDepartment of Gastroenterology and Hepatology, Saiseikai Suita Hospital
  • , Kanji YamaguchiAffiliated withDepartment of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
  • , Hironori MitsuyoshiAffiliated withDepartment of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
  • , Masahito MinamiAffiliated withDepartment of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
  • , Kohichiroh YasuiAffiliated withDepartment of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
  • , Yoshito ItohAffiliated withDepartment of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
  • , Toshikazu YoshikawaAffiliated withDepartment of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
  • , Michiaki FukuiAffiliated withDepartment of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
    • , Goji HasegawaAffiliated withDepartment of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
    • , Naoto NakamuraAffiliated withDepartment of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
    • , Mitsuhiro OhtaAffiliated withDepartment of Medical Biochemistry, Kobe Pharmaceutical University
    • , Hiroshi ObayashiAffiliated withDepartment of Molecular Biochemistry, Institute of Bio-Response Informatics
    • , Takeshi OkanoueAffiliated withDepartment of Gastroenterology and Hepatology, Saiseikai Suita HospitalDepartment of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Email author 

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Abstract

Background

Hyperlipidemia, insulin resistance, and oxidative stress can heavily contribute to the initiation and progression of nonalcoholic fatty liver disease (NAFLD). Currently, there is no established treatment for this disease. Recently, several studies have shown that ezetimibe (EZ), a lipid-lowering drug, attenuates liver steatosis in an experimental NAFLD model. This study was designed to assess the efficacy of long-term EZ monotherapy in patients with NAFLD.

Methods

A total of 45 patients with newly diagnosed liver biopsy-proven NAFLD were treated with EZ (10 mg/day) for 24 months. NAFLD-related biochemical parameters, imaging by computerized tomography, and liver biopsy were studied before and after treatment.

Results

Ezetimibe therapy significantly improved NAFLD-related metabolic parameters including visceral fat area, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-R), triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-Ch), oxidative-LDL, the net electronegative charge modified-LDL, profiles of lipoprotein particle size and fatty acids component, and estimated desaturase activity. EZ therapy also significantly lowered serum alanine aminotransferase and high-sensitivity C-reactive protein levels, whereas no significant changes were found in serum type IV collagen 7S, adiponectin, leptin, and resistin levels. Histological features of steatosis grade (P = 0.0003), necroinflammatory grade (P = 0.0456), ballooning score (P = 0.0253), and NAFLD activity score (NAS) (P = 0.0007) were significantly improved from baseline. However, the fibrosis stage was not significantly (P = 0.6547) changed.

Conclusion

The results in this study suggest that the long-term EZ therapy can lead to improvement in metabolic, biochemical, and histological abnormalities of NAFLD. Therefore, EZ may be a promising agent for treatment of NAFLD.

Keywords

Ezetimibe NAFLD Insulin resistance Lipid metabolism Fatty acid metabolism