However, decreasing Spp1 mRNA levels by AAV8-U6-shSpp1 fails to lower hepatocyte CEBPA knockout-potentiated fatty liver, liver inflammation, and serum ALT during MASH, suggesting that it is less likely that hepatocyte-derived OPN promotes liver fibrosis dependent on its modulation of hepatic steatosis, inflammation, and hepatocyte death during MASH. Here, SPP1 is linked to metabolic dysfunction-associated steatohepatitis.