Low 25-hydroxyvitamin D level is independently associated with non-alcoholic fatty liver disease

Abstract

Background and aims: We sought to explore associations between serum 25-hydroxyvitamin D [25(OH)D] levels and non-alcoholic fatty liver disease [NAFLD] in an integrated healthcare delivery system in the U.S.

Methods and results: Six hundred and seven NAFLD cases were randomly matched 1:1 with controls for age, sex, race and season of measurement. Conditional logistic regression was used to evaluate if serum 25(OH)D levels were associated with increased odds of NAFLD (diagnosed by ultrasound) after adjusting for body mass index and history of diabetes, renal, peripheral vascular and liver diseases (model 1) and also for hypertension (model 2). Mean (SD) serum 25(OH)D level was significantly lower in the group with NAFLD as compared with that in the matched control group (75 ± 17 vs. 85 ± 20 nmol/L [30 ± 7 vs. 34 ± 8 ng/mL], P<0.001). Inadequate 25(OH)D status progressively increased the odds of NAFLD when classified categorically as sufficient (25(OH)D 75 nmol/L [>30 ng/mL], reference group), insufficient (37-75 nmol/L [15-30 ng/mL]; adjusted odds ratio [OR]: 2.40, 95% confidence interval [CI]: 0.90-6.34) or deficient (<37 nmol/L [<15 ng/mL]; adjusted OR: 2.56, 95% CI: 1.27-5.19). When modeled as a continuous variable, increased log10 25(OH)D was inversely associated with the risk of prevalent NAFLD (adjusted OR: 0.25, 95% CI: 0.064-0.96, P=0.02).

Conclusion: Compared with matched controls, patients with NAFLD have significantly decreased serum 25(OH)D levels, suggesting that low 25(OH)D status might play a role in the development and progression of NAFLD.

Keywords: 25(OH)D; Fatty liver; Inflammation; NAFLD; Risk factors; Vitamin D.

Figure 1. Circulating 25(OH)D Levels in Cases vs. Controls

Box-plots of serum 25-hydroxyvitamin D [25(OH)D] levels in non-alcoholic fatty live disease (NAFLD) cases vs. controls. Middle line indicates median, borders of the box indicate the 25^th to 75^th percentile, whiskers indicate the 10^th and 90^th percentile, and dots indicate 5^th and 95^th percentile. * P < 0.0005 vs. control.

Figure 2. Odds Ratios of NAFLD

Logistic regression odds ratios (OR; 95% confidence interval [CI]) of non-alcoholic fatty liver disease [NAFLD] according to serum 25-hydroxyvitamin D [25(OH)D] level compared to sufficient (>75 nmol/L [>30 ng/mL]) reference group (gray bars: insufficient (37–75 nmol/L [15–30 ng/mL]); white bars: deficient (<37 nmol/L [<15 ng/mL]). Regression model 1 is adjusted for BMI and history of diabetes, renal disease, peripheral vascular disease and liver disease. Regression model 2 is further adjusted for hypertension.