Association of Vitamin D Deficiency to Liver Enzyme Status in Nonalcoholic Fatty Liver Disease in Veterans: A Retrospective Analysis

Abstract

Purpose: Vitamin D is a lipophilic molecule with anti-inflammatory, antifibrotic, immunomodulatory effects. Prior studies indicate a high prevalence of vitamin D deficiency in patients with nonalcoholic fatty liver disease (NAFLD). NAFLD is now considered a hepatic component of the metabolic syndrome and increases the risk of cardiovascular disease. The prevalence of NAFLD is observed in 20-30% of general population.In this study, we explore the relationship and extent of vitamin D deficiency to normal and abnormal liver enzymes among veterans with NAFLD and assess improvement in liver enzyme status with vitamin D supplementation. Methods: A retrospective review of electronic medical records of patients with a diagnosis of NAFLD at Veterans Affairs Medical facilities in the Southeastern United States was conducted. Those with one serum 25(OH) vitamin D level drawn between 2001-2008 were included and monitoring of 25(OH)D level over three subsequent years was noted. Patient demographic, initial and follow-up vitamin D values along with liver function were recorded. Vitamin D deficiency was defined as a value less than 20 ng/ml. The normal values for AST and ALT were less than 40 units and alkaline phosphatase 44-147 units/L. Vitamin D supplementation with ergocalciferol or cholecalciferol was also noted. Results: There were 376 veterans with NAFLD and an available 25(OH) vitamin D level. 44% had abnormal liver enzymes. Patients with abnormal liver enzymes were 53% more likely to be vitamin D deficient. Liver enzymes status did predict compliance vitamin D monitoring among study patients. Supplementation with any type of vitamin D was not associated with improvement in liver enzymes.Table: Table. Liver enzyme status and vitamin D variablesTableConclusion: Our data suggest that veterans with abnormal liver enzymes are more likely to be vitamin D deficient. Vitamin D deficiency could be due to impaired liver 25-hydroxylation that is a manifestation of disease severity. Vitamin D is implicated in insulin resistance that contributes to NAFLD. Vitamin D supplementation did not improve liver enzymes which could be due to need for robust replacement with vitamin D, patient non compliance for follow up. Increasing hepatocyte damage in NAFLD leads to decreased expression of VDR for any replaced vitamin D level to provide positive effect on liver enzyme values.Vitamin D3 appears to be approximately 87% more potent in raising and maintaining a sustained serum 25(OH)D level than D2. In our study, ergocalciferol was used to a little more extent than cholecalciferol.The lack of improvement in liver enzymes could also be explained by inability of ergocalciferol to maintain an adequate serum vitamin D level.