Genetics and Epigenetics in the Clinic: Precision Medicine in the Management of Fatty Liver Disease

Abstract

This narrative review will discuss the current evidence supporting the possible application of precision or personalized medicine to the management of nonalcoholic or “metabolic” fatty liver disease (NAFLD), based on recent progress in the understanding of the genetics and epigenetics of the disease. The prevalence of NAFLD, which can progress to cirrhosis and hepatocellular carcinoma, is constantly increasing worldwide. Accurate noninvasive predictors of liver disease progression, as well as of cardiovascular complications of NAFLD, are urgently needed. Evidence is now reporting that the genetic and epigenetic factors involved in NAFLD development can be used to develop risk scores for liver-related complications, which may show the possibility to implement programs for targeted screening and surveillance of complications. Moreover, genetic and epigenetic factors identifying specific sub-phenotypes of NAFLD can predict the individual response to pharmacological therapies. Finally, we describe opportunities for gene-targeted therapeutic approaches in NAFLD, where the genetic variants represent therapeutic targets for precision therapy approaches.

A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement

“…MAFLD may, in the future, be sub-classified based on new knowledge that might indicate the predominant pathophysiological pathway that drives the development of a morphologically limited set of histological features (steatosis, ballooning, inflammation and fibrosis) but which leads to different clinical outcomes. Such sub-classification will be particularly valuable for MAFLD given its substantial heterogeneity [57][58][59]. Thus, while we suggest the umbrella term MAFLD, it is in the knowledge that further sub-classification will likely ensue.…”

Genetic predisposition similarities between NASH and ASH: Identification of new therapeutic targets

“…Genetics is highlighting at the same time the sources of heterogeneity and possible ways for treatment personalization. Nowadays, molecular genetics is providing new tools to directly manipulate a wide array of potential disease pathways in the liver [24,25]. In this review, we will discuss the common genetic mechanisms underlying both NASH and ASH, and their possible use to design innovative therapeutic approaches.…”

Perspectives on Precision Medicine Approaches to NAFLD Diagnosis and Management

“…Precision medicine approaches in NAFLD treatment are still in their infancy [ 5 , 6 , 22 ]. Indeed, more information needs to be gathered to generate tailored therapeutic plans to the different and heterogenous patient categories grouped under the acronym NAFLD.…”

“…Recent advances in our knowledge of NAFLD genetics and in systems biology have fueled the potential application of precision medicine approaches to this disease [ 5 , 6 , 22 ]. In the present review article, we aim at providing a critical overview of selected research topics that relate to a more precise sub-phenotyping of patients with NAFLD based on sex and reproductive status, genetics, intestinal microbiota diversity, endocrine and metabolic status, as well as the degree of physical activity.…”