[31] BMP-1 is secreted by the liver, but protease inhibitors, such as alpha-2-macroglobulin (A2M), are also secreted by the liver, often at elevated levels in inflammation or chronic disease.[32] Either a reduction in BMP-1, or an increase in inhibitors such as A2M - as reportedly occurs in HCC [33], could block the maturation of pro-Apolipoprotein A1, hence contributing to relative increase in this isoform (spot 3). This evidence concerns the gene APOA1 and hepatocellular carcinoma.