Long-Term Effect of PNPLA3 on the Aggravation of Nonalcoholic Fatty Liver Disease in a Biopsy-Proven Cohort.

The PNPLA3 rs738409 G allele increases the risk of not only nonalcoholic fatty liver disease (NAFLD) but also nonalcoholic steatohepatitis (NASH) or fibrosis. It also affects the prognosis of patients with NAFLD in specific conditions. After liver transplantation, patients with NAFLD carrying the rs738409 GG genotype have a higher risk of graft steatosis or development of hepatocellular carcinoma. In addition, rs738409 modifies the effects of medical intervention: patients with NAFLD carrying the GG genotype showed a lower effect of omega-3 polyunsaturated fatty acid treatment on the reduction of liver fat; in contrast, they were more sensitive to the beneficial effects of lifestyle modifications..