Efficacy and Safety of Roflumilast in Patients with Non-Alcoholic Steatohepatitis: A Randomized Controlled Study
Tarek Mohamed Mostafa
Clinical Pharmacy Department, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
Mokhtar Salem Mohamed
*
Clinical Pharmacy Department, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
Sherief M Abdel-salam
Department of tropical medicine and Infectious disease, Faculty of Medicine, Tanta University, Tanta, Egypt.
Dalia Refaat El-Afify
Clinical Pharmacy Department, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
*Author to whom correspondence should be addressed.
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.
Keywords: NASH, roflumilast, PDE-4, LSM, TNF-α, MDA, TGF-ß1, ALT, AST, lipid profile, OMA-IR