Vitamin D levels and liver histological alterations in children with nonalcoholic fatty liver disease

Abstract

Objective: To investigate the association between plasma vitamin D (VD) levels and histological liver damage in children with nonalcoholic fatty liver disease (NAFLD). Subjects and methods: In this cross-sectional study, carried out in a tertiary care center for obesity, 73 consecutive overweight and obese children with persistently elevated serum aminotransferase levels and diffusely hyperechogenic liver on ultrasonography were selected for liver biopsy. Nonalcoholic steatohepatitis (NASH) and fibrosis were histologically diagnosed using NAFLD Clinical Research Network (CRN) criteria. The plasma levels of 25-OH-VD were measured by HPLC. Bone mineral density (BMD) of lumbar spine was evaluated by dual-energy X-ray absorptiometry. Multiple linear regression analysis was used to evaluate the association between 25-OH-VD levels and the predictors of interest after correction for age, gender, waist circumference, BMI, and other potential confounders. Results: The children (64% males) were aged 8-18 years, and their median BMI was 2.45 SDS. Both parathyroid hormone levels and BMD were within the normal range. All cases of fibrosis were detected in children with NASH. On multivariable linear regression with correction for age, gender, and BMI, 25-OH-VD levels were found to be 9 (95% CI 12-6) ng/ml lower in children with NASH than in those without NASH (P!0.001) and 9 (12-6) ng/ml lower in children with stage 1 fibrosis than in those with stage 0 fibrosis and 9 (13-6) ng/ml lower in children with stage 2 than in those with stage 0 fibrosis (P!0.001 for both). Conclusion: VD levels are inversely associated with NASH and fibrosis in children with NAFLD.

Severe Vitamin D Deficiency May be an Additional Cofactor for the Occurrence of Alcoholic Steatohepatitis

“…Among studies that assessed the liver with a liver biopsy, 2 studies conducted on overweight and obese children and 1 study conducted on overweight adults found an inverse association between the level of 25-OH vitamin D and the severity of steatosis, inflammation, ballooning, and fibrosis (Manco et al, 2010;Nobili et al, 2014;Targher et al, 2007). By contrast, this association was not found in a recently published large cohort of obese patients (Bril et al, 2015).…”

Nonalcoholic fatty liver disease and decreased bone mineral density: is there a link?

“…Epidemiological studies, involving patients with non-cirrhotic NAFLD, have suggested that low levels of serum 25-hydroxyvitamin D 3 are associated with a greater severity of NAFLD histology, independent of several potential confounders, including the features of MetS [16,[58][59][60][61]. Although it could be also hypothesized the existence of reverse causality between NAFLD and low serum 25-hydroxyvitamin D 3 levels, some experimental studies have shown that the liver expression of both CYP2R1 and CYP27A1 (i.e., two cytochromes implicated in the 25-hydroxylation of vitamin D 3 ) is preserved in patients with NASH or chronic hepatitis C virus [62].…”

The Progression and Natural History of Pediatric Nonalcoholic Fatty Liver Disease

“…Vitamin D deficiency, defined as vitamin D 25-OH levels < 20ng/ml, was present in 50% of 64 children with NAFLD [51]. In a follow-up study of 73 overweight and obese Italian children with NAFLD, vitamin D 25-OH levels were significantly lower in those children with NASH than those without NASH [52]. In contrast, in a study of 102 children in the NASH CRN, although low vitamin D 25-OH levels were common there was no association with the histologic severity of disease [53].…”