Association between nonalcoholic fatty liver disease and metabolic parameters, controlled attenuation parameter, transient elastography,PNPLA3 RS738409 and TM6SF2 RS58542926 gene variants

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder and encompasses a histological spectrum that ranges from simple steatosis (NAFL) to nonalcoholic steatohepatitis (NASH). We aimed to investigate associations between NAFLD and metabolic syndrome, components of this syndrome, noninvasive methods such as controlled attenuation parameter and ultrasound which detect steatosis, transient elastography which is another noninvasive method detecting stiffness of liver, two single nucleotide polymorhisms found in exome wide studies named as PNPLA3 rs738409 and TM6SF2 rs58542926. After excluding alcohol intake and secondary causes of hepatosteatosis; we investigated labaratory, imaging and anthropometric features as well as results of sequencing of two genes mentioned of 234 healthy individuals admitted to the check-up department of the hospital. While grade 2 and 3 steatosis detected by ultrasound could predict hepatosteatosis accurately, grade 0 and 1 could not differentiate hepatosteatosis and normal liver in accordance with CAP measurements. We observed higher degree of steatosis among indiviuals with high body mass index, insulin resistance, male sex, metabolic syndrome, high trigyceride, high GGT and low HDL levels, respectively. Liver was stiffer in subjects with high liver enzymes and insulin resistance. PNPLA3 gene variant was associated solely with high GGT levels. However, homozygosity for this SNP was associated with higher liver stiffnes, high ALT anf GGT levels. Except for low triglyceride levels, there were no differences in any parameter between normal and heterozygote individuals for TM6SF2 gene variant. NAFLD is a multifactorial disorder with insulin resistance playing an important role in every stage. Individuals who are overweight and have insulin resistance are most likely to have simple steatosis, while high liver stiffness and liver enzymes are more predictive for NASH in clinical practice. PNPLA3 gene variant is associated with necroinflammatory component of NASH rather than steatosis especially in homozygous state. TM6SF2 gene variant appears to be not associated with NAFLD.