Innovative Therapeutic Approaches in Non-Alcoholic Fatty Liver Disease: When Knowing Your Patient Is Key

Abstract

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of disorders ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Hepatic steatosis may result from the dysfunction of multiple pathways and thus multiple molecular triggers involved in the disease have been described. The development of NASH entails the activation of inflammatory and fibrotic processes. Furthermore, NAFLD is also strongly associated with several extra-hepatic comorbidities, i.e., metabolic syndrome, type 2 diabetes mellitus, obesity, hypertension, cardiovascular disease and chronic kidney disease. Due to the heterogeneity of NAFLD presentations and the multifactorial etiology of the disease, clinical trials for NAFLD treatment are testing a wide range of interventions and drugs, with little success. Here, we propose a narrative review of the different phenotypic characteristics of NAFLD patients, whose disease may be triggered by different agents and driven along different pathophysiological pathways. Thus, correct phenotyping of NAFLD patients and personalized treatment is an innovative therapeutic approach that may lead to better therapeutic outcomes.

Keywords: fatty liver; patient phenotyping; personalized medicine; steatohepatitis.

Figure 1

Non-alcoholic fatty liver disease (NAFLD) includes a spectrum of liver manifestations ranging from steatosis to cirrhosis. Progression of the disease is determined by different pathological pathways, mainly metabolism impairment and liver inflammation, which are influenced by patients’ lifestyles, genetics, microbiomes and environmental factors. Interventions on these factors could promote regression at early stages of the disease.

Figure 2

Non-alcoholic fatty liver disease (NAFLD) includes a wide spectrum of patients whose phenotype is determined by the different affection of key processes involved in the pathophysiology of the disease, including body weight and composition, the presence of metabolic syndrome and type 2 diabetes mellitus, liver histological features, genetic predisposition, the use of toxic substances such as small amounts of alcohol and steatogenic drugs, infections and alterations in the gut microbiome, development of vascular disease and systemic inflammation.