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Vitamin D may be protective against apoptosis in patients with non-alcoholic steatohepatitis (NASH)
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Speaker:
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Zobair Younossi
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Author:
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A. Birerdinc1,2, M. Abawi2, M. Stepanova1, A. Afendy1,3, A. Baranova1,2, Z. Goodman1, Z. Younossi1,3*
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Affiliation:
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1Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, 2Center for the Study of Genomics in Liver Diseases, School of Systems Biology, George Mason University, Fairfax, 3Center for Liver Diseases and Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, USA. *zobair.younossi@inova.org
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Background and aim: Vitamin D has been implicated in cell differentiation, proliferation, maturation and the regulation of apoptosis. Apoptosis is thought to be central to the pathogenesis of NASH. M30, which is caspase cleaved CK18, is a specific marker for apoptosis. The relationship between Vitamin D and apoptosis in NAFLD has not been fully studied.
Methods: Fasting serum samples, liver biopsies, clinical and laboratory data were collected for biopsy-proven NAFLD patients. All liver biopsies were interpreted by a single hepatopathologist. Serum samples were assayed for Vitamin D levels using 25(OH)-Vitamin D3 assays (Alpco, Salem, NH) and for M30 (Peviva, Broma, Sweden). ASBMR criteria for Vitamin D deficiency were used. Descriptive statistics and Mann-Whitney U-tests were calculated. Correlations were assessed by Pearson's coefficient and non-parametric rank test. Significance of trends was evaluated using Chi-square tests.
Results: A total of 210 biopsy-proven NAFLD patients (44.8% NASH, 32.4% type 2 diabetes, 58.6% insufficient for Vitamin D, age 44.7 +/-11 years, BMI 46 +/-11.7, AST 30.3 +/-43.5, ALT 35.8 +/-29, 21% receiving Vitamin D or multivitamin supplementation) were included. Of 44 NAFLD patients taking Vitamin D supplementation, 43.2% (n=19) had NASH, 27.3% (n=12) had advanced hepatic fibrosis as defined by fibrosis stageā„2. NASH patients who were not receiving Vitamin D supplementation had higher levels of M30 than non-NASH (296 vs.172, p< 0.00003). In a similar analysis, NAFLD with advanced fibrosis had higher M30 levels regardless of Vitamin D supplementation [with Vitamin D (248 vs. 145, p< 0.009), without Vitamin D (279 vs. 206, p< 0.005)].
Conclusion: Vitamin D supplementation seems to have an effect on the levels of apoptosis on histologic NASH but not advanced fibrosis. These data suggest that the protective effects of Vitamin D may be subject to a systemic damage threshold. Further research is warranted to elucidate the impact of Vitamin D on apoptosis in NAFLD.
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