The liver plays a central role in the synthesis of vitamin D (Vit D). Through its receptor, Vit D inhibits cell differentiation and proliferation, promotes cell maturation and participates in the regulation of apoptosis. Apoptosis has been shown to play a key role in the pathogenesis of NAFLD and its progressive form or Non-Alcoholic Steatohepatitis (NASH). Vitamin D deficiency is also associated with inflammation and insulin resistance and has been commonly found in obese patients at risk for NAFLD.

Methods: Fasting serum samples, liver biopsies, clinical and laboratory data were collected for 104 morbidly obese NAFLD patients. Serum samples were assayed for Vit D levels using 25(OH)-Vitamin D3 assays (Alpco). ASBMR criteria for Vitamin D deficiency were used. All liver biopsies were interpreted by a single hepatopathologist. For a subset of NAFLD patients, serum levels of adiponectin, resistin, total CK18 (M65, a measurement of overall cell death due to both apoptosis and necrosis) and caspase cleaved CK18 (M30, a specific measurement of apoptosis) were available. Descriptive statistics and Mann-Whitney Utests were calculated. Correlations were assessed by Pearson’s coefficient and non-parametric rank test. Significance of the trends was evaluated using Chi-square tests.

Results: A total of 104 obese patients with biopsy-proven NAFLD were included. Direct comparison of the Vit D levels in NASH (62.8 +/- 38.1 nmol/l) and non-NASH NAFLD (43.6 +/-27.2 nmol/l) patients were different (P < 0.007). Analysis of correlations in a subset of these patients (n=21) showed that Vit D levels correlated with serum M30 as a marker of apoptosis (R = 0.5228, p < 0.02), but not with serum resistin, adiponectin or M65. Interestingly, when only NASH patients (N=13) were considered, correlation between apoptosis (M30) and Vit D became even more prominent (R=0.6911, p < 0.01).

Conclusion: Our finding supports role of Vit D in apoptosis associated with NASH. The relationship between Vit D levels and NAFLD is probably more complex than previously suggested.