Genes and lifestyle: Which of the two is more relevant in driving NAFLD progression?

A wide spectrum of factors conjointly operate in the pathogen- esis of NAFLD and in liver disease progression towards advanced liver disease and comorbidities [1]. At one extreme we find ge- netic factors: they provide mechanism(s) facilitating liver fat accu- mulation well before birth, as expressed by epigenetic studies [2], and are operative throughout life. In recent years several studies have shown that a lot of gene polymorphisms are associated with an increased risk of NAFLD, variably linked with obesity, with the risk of cardiovascular events, with the risk of progression to hep- atocellular cancer [3]. They have expanded to the area of NAFLD solid concepts linking non-communicable diseases to familial clus- tering and studies in homozygotic/dizygotic twins [4]. A few genes may also drive different outcomes, or make individuals more re- sistant to NAFLD development (protective genes) [5]. Scores have been generated to predict risks, although based on the number of mutated alleles, without any balance according to risk severity [6].