Vitamin D in liver cancer: novel insights and future perspectives

Abstract

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.

Prognostic Significance of Severe Vitamin D Deficiency in Patients with Primary Sclerosing Cholangitis

“…This might be related to vitamin D properties, including anti-proliferative, anti-angiogenic, proapoptotic, and prodifferentiative effects [ 30 ]. However, the main impact of vitamin D in hepatocellular carcinoma seems to be the inhibition of cell proliferation [ 31 ]. In a German prospective cohort study, a severe vitamin D deficiency was associated with advanced stages of hepatocellular carcinoma and a higher mortality risk.…”

“…This association was independent of the MELD score and alpha-fetoprotein levels [ 20 ]. Although the results of observational studies regarding the association between vitamin D status and liver cancer development are promising, they are still inadequate [ 31 ]. In a retrospective study of cholangiocarcinoma patients, vitamin D intake was associated with shorter disease-free survival in patients who underwent surgery [ 32 ].…”

“…In patients with Crohn’s disease, the frequency of vitamin D deficiency was estimated to be as high as 70% [ 30 ]. PSC occurrence was an independent predictor of vitamin D deficiency (≤50 nmol/L) in patients with Crohn’s disease and ileal pouch–anal anastomosis (odds ratio: 7.56; 95% CI: 2.39–24.08; p = 0.001) [ 31 ].…”

Immunomodulatory actions of vitamin D in various immune-related disorders: a comprehensive review

“…The association between the serum level of vitamin D and the risk of various cancers has been investigated several times in the past. Colorectal cancer (176), breast cancer (177), skin cancer (178), prostate cancer (179), liver cancer (180), and head and neck cancers (181) are some of the examples. According to Ma et al's study, high blood levels of vitamin D was correlated with a 33% reduction in the risk of colorectal cancer (182).…”