ENPP2 and hepatocellular carcinoma: In pancreatic ductal adenocarcinoma (PDAC), LPCs secreted from activated pancreatic stellate cells could be hydrolyzed by ENPP2, which was produced by PDAC, and finally promoted pancreatic tumor progression via the ENPP2/LPA axis (Auciello et al., 2019; Biffi and Tuveson, 2019), so in future, we need to clarify if aHSC may also secrete LPCs acting as a major substrate for ENPP2, and if HBV induces HCC progression not only by autocrine ENPP2, but also transfers the microenvironment to benefit HCC survival via the LPC/ENPP2/LPA axis in HBV-related HCC patients.