Non-alcoholic fatty liver disease and type 2 diabetes mellitus. II. Treatment

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease. Non-alcoholic steatohepatitis (NASH), the aggressive form of NAFLD can progress to cirrhosis, and is becoming the leading cause of end-stage liver disease. NAFLD and NASH are prevalent in obese individuals and frequently coexist with type 2 diabetes mellitus as well as cardiovascular and renal complications. There is no approved therapy for the treatment of NAFLD and NASH. Their current management focuses on controlling risk factors, and lifestyle modification, weight reduction, caloric restriction, diet and exercise, but these can be difficult to achieve and maintain. Thus, there is an urgent need for effective pharmacotherapy. This review summarizes pharmacological agents available to treat diabetes mellitus, the main risk factor of NAFLD, drugs that could potentially be useful also for the therapy of NASH. Furthermore, we describe novel therapies targeting different pathogenic pathways of NAFLD, several agents that are under development specifically for the treatment of NASH. These new classes of medications may target hepatic fat accumulation, de novo lipogenesis, farnesoid X receptor-bile acid axis, oxidative stress, inflammation, gut microbiome and fibrogenesis. Until now, the use of pioglitazone and vitamin E has only been recommended by guidelines for selected patient groups with biopsy-proven NASH. It is likely that in the future, the combination of different types of targeted pharmacotherapies will provide an effective treatment for NASH. Since NAFLD is a systemic metabolic disease, cooperation between diabetologists, nephrologists, cardiologists and hepatologists is also highly advised in the management of these patients.