%0 Journal Article
%T Nonalcoholic fatty liver disease: is the IFNL4 rs368234815 variant  protective from liver damage?
%A Enrico Galmozzi
%A Roberta D¡¯Ambrosio
%J SCIE-indexed Journal
%D 2018
%X Nonalcoholic fatty liver disease (NAFLD) consists of a spectrum of disorders characterized predominantly by hepatic steatosis in the absence of significant alcohol consumption, potentially evolving to nonalcoholic steatohepatitis (NASH), with increased hepatocellular injury and inflammation with or without fibrosis. Factors promoting deposition of fat in the liver include obesity, diabetes, insulin resistance, and alcohol ingestion (1). Racial and ethnic differences have been reported in the prevalence of NAFLD, which is most common in East Asian Indians followed by Hispanics, Asians, Caucasians, and less frequently in African Americans (2-4). Although the reasons for these ethnic differences are still unknown, inherited factors has been found play a major role in the susceptibility to NAFLD and in its severity. Indeed, genetic elements such as the common variants in the patatin-like phospholipase domain-containing protein 3 (PNPLA3) and transmembrane 6 superfamily member 2 genes (TM6SF2) have been strongly associated not only with the development but also with the histological progression of liver damage in NAFLD patients (5,6). However, the variants in the interferon lambda (IFNL) 3/4 locus were associated with the liver fibrosis progression in hepatitis C virus (HCV) patients only (7), while contrasting results have been reported in subjects with NAFLD (8,9). In this context, the study by Petta et al., conducted on a large cohort of Italian patients, adds important information about the independent role of IFNL4 variants in the pathogenesis of NAFLD-related liver damage (10). The IFNL4 gene harbors the rs12979860 C>T polymorphism (commonly referred to as IL28B) in strong linkage with the causal variant rs368234815 TT/¦¤G, whose ¦¤G allele generates the open reading frame for the IFN¦Ë4 protein associated with either spontaneous or IFN-induced HCV clearance (11,12). Petta and colleagues reported a similar distribution rate of the IFNL4 variants among the 946 patients with a histological diagnosis of NAFLD and the 379 healthy controls, thus suggesting that IFNL4 polymorphisms do not confer per se a risk toward hepatic fat accumulation. However, in the cohort of NAFLD patients after correction for clinical/metabolic risk factors and for PNPLA3 genotype as well as for NASH, the common IFNL4 rs368234815 TT allele emerged as a major determinant of liver damage in terms of severity of fibrosis (F3-F4 by Kleiner classification). As expected, similar results were observed also for the linked common rs12979860 C allele. Furthermore, the IFNL4 variants were
%U http://hbsn.amegroups.com/article/view/18965/19837