Vitamin D in liver cancer: novel insights and future perspectives.

Vitamin D has been a focus of attention in liver cancer due to its direct and indirect antineoplastic effects. This review critically evaluates data from recently published basic and clinical studies investigating the role of vitamin D in liver cancer. Basic studies indicate that vitamin D plays an important role in liver cancer development by suppressing the activity of hepatic stellate cells and Kupffer cells. Furthermore, vitamin D has a direct anti-proliferative, anti-angiogenic, proapoptotic, and prodifferentiative effect on liver cancer cells. Recent investigation suggested several interesting mechanisms of these actions, such as inactivation of Notch signaling, p27 accumulation, and tyrosine-protein kinase Met/extracellular signal-regulated kinases inhibition. On the other hand, data from clinical observational studies, although promising, are still inconclusive. Unfortunately, studies on the effect of vitamin D supplementation were generally focused on short-term outcomes of chronic liver diseases (liver enzyme levels or elastographic finding); therefore, there are still no reliable data on the effect of vitamin D supplementation on liver cancer occurrence or survival.