The role of ATP released by damaged cells in the extracellular space, the activation of the P2X7 receptor, together with the involvement of NLRP3 inflammasome and pro-inflammatory cytokines production is now also well-proven in the liver, with substantial evidence showing the involvement of the P2X7 receptor/NLRP3 inflammasome in the induction of NAFLD/NASH and liver fibrosis, at least in animal models, involving the modulation of hepatocytes, and Kupffer and stellate cell activity. This evidence concerns the gene P2RX7 and metabolic dysfunction-associated steatohepatitis.