Efficacy and Safety of Roflumilast in Patients with Non-Alcoholic Steatohepatitis: A Randomized Controlled Study

Abstract

Background: Non-alcoholic fatty liver disease is the most prevalent chronic liver disease globally. There is no defined therapy for non-alcoholic steatohepatitis (NASH). Aim: This study aimed at evaluating the efficacy and safety of Roflumilast in patients with non-alcoholic NASH. Methods: This randomized controlled parallel study involved 55 patients with NASH who were randomized into vitamin E group or control group (n=24) which received vitamin E 1000 mg once daily and roflumilast group (n=31) which received roflumilast 500 μg once daily for three months. Patients were assessed at baseline and after intervention through liver stiffness measurement (LSM) using fibro-scan and through evaluation of serum levels of tumor necrosis factor –alpha (TNF-α), Malondialdehyde (MDA), transforming growth factor-beta 1 (TGF-ß1). In addition, liver enzymes, lipid panel, fasting blood glucose and fasting insulin level with subsequent calculation of homeostatic model assessment for Insulin resistance (HOMA-IR) were also assessed. Results: Compared to the control group, after 3 months of roflumilast treatment resulted in a non-significant reduction in body weight and body mass index (P=0.126), (P=0.713) respectively, significant improvement in liver enzymes, blood glucose, HOMA-IR, triglyceride, TNF-α, MDA, TGF-ß1 levels and significant improvement in liver stiffness (all P<0.001). In addition, oral roflumilast proved safety in patients with NASH since it doesn't provoke any serious adverse reaction. Conclusion: Roflumilast may be a promising therapy for NASH as it may decrease hepatic steatosis and fibrosis through its anti-inflammatory and anti-oxidative effect.