Focus on emerging drugs for the treatment of patients with non-alcoholic fatty liver disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disorder in Western countries and is increasingly being recognized in developing nations. Fatty liver disease encompasses a spectrum of hepatic pathology, ranging from simple steatosis to non-alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma and end-stage liver disease. Moreover, NAFLD is often associated with other metabolic conditions, such as diabetes mellitus type 2, dyslipidemia and visceral obesity. The most recent guidelines suggest the management and treatment of patients with NAFLD considering both the liver disease and the associated metabolic co-morbidities. Diet and physical exercise are considered the first line of treatment for patients with NAFLD, but their results on therapeutic efficacy are often contrasting. Behavior therapy is necessary most of the time to achieve a sufficient result. Pharmacological therapy includes a wide variety of classes of molecules with different therapeutic targets and, often, little evidence supporting the real efficacy. Despite the abundance of clinical trials, NAFLD therapy remains a challenge for the scientific community, and there are no licensed therapies for NAFLD. Urgently, new pharmacological approaches are needed. Here, we will focus on the challenges facing actual therapeutic strategies and the most recent investigated molecules.

Keywords: Non-alcoholic steatohepatitis, Non-alcoholic fatty liver disease, Fatty liver, Steatosis, Emerging drugs

Core tip: At the moment, there is no standardized treatment for non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH); the first-line approach remains lifestyle changes (diet and physical exercise). The high risk of complications associated with NAFLD/NASH, such as cardiovascular diseases and the incidence of hepatocellular carcinoma, make it necessary to apply appropriate medications to stop the progression of the disease. Considering the pathogenetic pathways known today, several therapeutic targets have been proposed, including some that look very promising; still, innovative pharmacological strategies are absolutely needed. Below, we report the real efficacies of fatty liver therapies and the most recent studies investigating this field.