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Vitamin D levels Non-Alcoholic Fatty Liver Disease (NAFLD) patients correlate with apoptosis and serum levels of M30
Massih Abawi, Aybike Birerdinc, Ancha Baranova, Arian Afendy, Sandra Page, Maria Stepanova, Zachary Goodman, Zobair M. Younossi

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.