Effect of PNPLA3, TM6SF2 and MBOAT7 Genetic Variants on Non-alcoholic Fatty Liver Disease Therapeutic Outcome.

Patatin-like phospholipase domain-containing protein-3 (PNPLA3), the transmembrane 6 superfamily member 2 protein (TM6SF2) and membrane bound O-acyltransferase domain containing 7 (MBOAT7) genes are involved in non-alcoholic fatty liver disease (NAFLD) development and worsening. Following the actual scientific knowledge, some studies have identified the genetic background surrounding NAFLD, counting up to forty different genetic variants that seem to exert also a crucial role in the disease evolution, according to the natural history, until hepatocellular carcinoma onset. However, few data exist regarding their influence on the treatment response. The aim was to explore the effect of 303 mg of silybin-phospholipids complex, 10 mg of vitamin-D and 15 mg of vitamin-E twice a day for six months in NAFLD patients carrying PNPLA3-rs738409, TM6SF2-rs58542926 and MBOAT7-rs641738 genetic variants. The assessed mutations are independently associated with no response to a silybin/vitamin D-based therapy and could be useful therapeutic predictive markers in this context.