Efficacy of probucol for the treatment of non-alcoholic steatohepatitis with dyslipidemia: An open-label pilot study
Tomokazu Ishitobi
Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan
Search for more papers by this authorCorresponding Author
Hideyuki Hyogo
Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan
Correspondence: Hideyuki Hyogo, Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minamiku, Hiroshima 734-8551, Japan. Email: [email protected]Search for more papers by this authorHironori Tokumo
Department of Gastroenterology and Hepatology, JA Hiroshima General Hospital, Hiroshima, Japan
Search for more papers by this authorKoji Arihiro
Department of Pathology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
Search for more papers by this authorKazuaki Chayama
Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan
Search for more papers by this authorTomokazu Ishitobi
Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan
Search for more papers by this authorCorresponding Author
Hideyuki Hyogo
Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan
Correspondence: Hideyuki Hyogo, Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minamiku, Hiroshima 734-8551, Japan. Email: [email protected]Search for more papers by this authorHironori Tokumo
Department of Gastroenterology and Hepatology, JA Hiroshima General Hospital, Hiroshima, Japan
Search for more papers by this authorKoji Arihiro
Department of Pathology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
Search for more papers by this authorKazuaki Chayama
Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan
Search for more papers by this authorAbstract
Aim
Oxidative stress plays a pivotal role in the transition from simple steatosis to non-alcoholic steatohepatitis (NASH). Probucol is a lipid-lowering agent with strong antioxidant properties, and is reported to be effective for the treatment of NASH in several studies. The aim of the present study was to evaluate the efficacy of probucol for the treatment of NASH with dyslipidemia.
Methods
Twenty-six patients with biopsy-proven NASH accompanied by dyslipidemia were treated with 500 mg of probucol daily for 48 weeks. Body mass index, visceral fat area, liver function tests, serum lipids, fibrosis markers, ferritin, adiponectin, leptin, urinary 8-hydroxy-2′-deoxyguanosine (U-8OHdG) and elasticity were measured periodically during the study. Follow-up liver biopsy was performed in 18 patients.
Results
Serum levels of aminotransferases, total cholesterol and U-8OHdG significantly decreased (P < 0.01). Levels of hemoglobin A1c (HbA1c), the Homeostasis Model of Assessment – Insulin Resistance index and serum levels of ferritin, type IV collagen 7S and hyaluronic acid significantly decreased (P < 0.05). The serum levels of adiponectin tended to be increased. Liver stiffness significantly decreased from 8.8 ± 6.8 to 6.6 ± 4.0 kPa (P < 0.01). Non-alcoholic fatty liver disease activity scores were significantly improved from 4.2 ± 1.4 to 3.4 ± 1.6 (P < 0.05) and fibrotic stages tended to be improved from 1.6 ± 0.8 to 1.3 ± 1.1, respectively. No adverse effects of this treatment were noted.
Conclusion
Probucol improved clinical and histological findings probably through its ability to reduce insulin resistance and oxidative stress. Probucol therapy was safe and effective for Japanese NASH patients with dyslipidemia.
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