HAS2 and cancer: 4,40 Also, HAS2 is crucial for HA production, cancer growth in cholangiocarcinoma, and liver metastasis caused by colorectal and pancreatic cancers.41,42 These findings indicate that HAS2 is the isozyme responsible for HA production in liver fibrosis and liver malignancy; HAS2 and HA are primarily expressed in HSCs; and HAS2 and HA contribute to HSC activation, liver fibrosis, and fibrosis-mediated cancer progression. These studies further suggest that reduced HA clearance and active HA synthesis determine the level of circulating HA in liver fibrosis (Figure 1).