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

• Published in: Journal of gastroenterology 2011, Vol.46 (1), p.101-107
• Main Authors: Park, Hyohun, Shima, Toshihide, Yamaguchi, Kanji, Mitsuyoshi, Hironori, Minami, Masahito, Yasui, Kohichiroh, Itoh, Yoshito, Yoshikawa, Toshikazu, Fukui, Michiaki, Hasegawa, Goji, Nakamura, Naoto, Ohta, Mitsuhiro, Obayashi, Hiroshi, Okanoue, Takeshi
• Format: Article
• Language: English
• Subjects: Abdominal Surgery; Adult; Anticholesteremic Agents - administration & dosage; Anticholesteremic Agents - therapeutic use; Azetidines - administration & dosage; Azetidines - therapeutic use; Biliary Tract; Biomarkers - blood; Biopsy; Care and treatment; Colorectal Surgery; Development and progression; Drug Administration Schedule; Ezetimibe; Fatty acid metabolism; Fatty acids; Fatty liver; Fatty Liver - blood; Fatty Liver - drug therapy; Fatty Liver - pathology; Female; Gastroenterology; Hepatology; Humans; Insulin resistance; Leptin; lipid metabolism; Liver - pathology; Liver Cirrhosis - classification; Liver Cirrhosis - pathology; Low density lipoproteins; Male; Medical colleges; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Middle Aged; NAFLD; Non-alcoholic Fatty Liver Disease; Original Article—Liver; Pancreas; Surgical Oncology; Treatment Outcome
• ISSN: 0944-1174; 1435-5922
• DOI: 10.1007/s00535-010-0291-8

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.