Can we stop the progression of chronic liver disease to hepatocellular carcinoma?

Transforming growth factor beta 1 (TGFβ1) and matrix metalloproteinase 8 (MMP-8) appear to play important roles in the pathogenesis of hepatocellular carcinoma (HCC). TGFβ1 is pro-fibrogenic while MMP-8 promotes metastasis by degrading collagens in the extracellular matrix. However, both of these molecules have tumor suppressing as well as tumor promoting properties. The study by Qin et al. examines the relationship between TGFβ1 and MMP-8 in tumor progression, and suggests that they operate reciprocally in a positive feedback loop. While this is an important observation that would ultimately benefit tumor bearing patients, there is also additional evidence that the consequences of altered TGFβ1 signaling and elevated MMP-8 expression impact the pathogenesis of chronic liver disease (CLD) long before the appearance of HCC. This raises the possibility that these molecules could be targeted and regulated early enough to delay or prevent the development of cirrhosis and/or HCC.