Genetic Contribution to Non-alcoholic Fatty Liver Disease and Prognostic Implications

Abstract

Purpose of Review Non-alcoholic fatty liver disease (NAFLD) is a major and increasing health burden, with the potential to overwhelm hepatology services. However, only a minority of patients develop advanced liver disease. The challenge is early identification of patients at risk of progression. This review aims to summarize current knowledge on the genetic predisposition to NAFLD, and its implications for prognostication and risk stratification. Recent Findings PNPLA3-I148M is the most robustly associated genetic variant with NAFLD. Recently, variants in TM6SF2, MBOAT7, GCKR and HSD17B13 have also been implicated. NAFLD is a complex disease, and any one genetic variant alone is insufficient for risk stratification, but combining multiple genetic variants with other parameters is a promising strategy. Summary It is anticipated that, in the near future, analysis of data from large-scale prospective cohorts will reveal NAFLD subtypes and enable the development of prognostic models. This will facilitate risk stratification of patients, enabling optimisation of resources to effectively manage the NAFLD epidemic.

Nonalcoholic Fatty Liver Disease: Focus on New Biomarkers and Lifestyle Interventions

“…Literature data indicate that the pathogenesis of NAFLD is closely linked with increased adiposity, dyslipidemia, and insulin resistance [9]. Recently, the influence of genetic factors in the development of hepatic steatosis, as well as its progression in more severe forms of liver disease, has been reported in both experimental and observational studies [10,11]. Genome wide association studies (GWAS) have demonstrated the presence of genetic variants associated with NAFLD [12].…”

Genetic Polymorphisms and Clinical Features in Diabetic Patients With Fatty Liver: Results From a Single-Center Experience in Southern Italy

“…There is a significant heterogeneity in the clinical phenotype and natural history of NAFLD because it is a multifactorial disease resulting from the interaction between the genetic background and environmental factors ( 4 ). Obesity, type 2 diabetes, reduced physical activity, and genetic variants are the most important risk factors; however, it is unclear which of them plays a decisive role in the disease promotion and progression.…”

“…Obesity, type 2 diabetes, reduced physical activity, and genetic variants are the most important risk factors; however, it is unclear which of them plays a decisive role in the disease promotion and progression. Therefore, in clinical practice, it is unknown which patients have the greatest risk of suffering from liver damage or developing liver cirrhosis ( 4 ).…”

Correlation between Non-Alcoholic Fatty Liver Disease (NAFLD) fibrosis score (NFS) with Left Ventricular Mass Index (LVMI) in patients with NAFLD

“…A number of non-invasive methods have been developed by combining clinical and serological variables that are able to determine the occurrence of advanced fibrosis in patients with NAFLD. 13 NAFLD fibrosis score (NFS) is one of the non-invasive methods that has been validated in its application for determining the degree of liver fibrosis in patients with NAFLD. NFS has been recommended by the American Association for Study of Liver Disease (AASLD), American College of Gastroenterology (ACG), American Gastroenterological Association (AGA) and by the European Association for the Study of the Liver (EASL).…”

“…NFS has been recommended by the American Association for Study of Liver Disease (AASLD), American College of Gastroenterology (ACG), American Gastroenterological Association (AGA) and by the European Association for the Study of the Liver (EASL). 13,14 NAFLD is known to be a risk factor for the occurrence of subclinical abnormalities in myocardial metabolism and is associated with subclinical changes over time in left ventricular structure function, which causes both structural and functional heart abnormalities. 14 Left ventricular mass index (LVMI) is an adjusted mass of the left ventricle to the total surface area of the body.…”