Relationship of vitamin D with insulin resistance and disease severity in non-alcoholic steatohepatitis

Bril, Fernando; Maximos, Maryann; Portillo-Sánchez, Paola; Biernacki, Diane; Lomonaco, Romina; Subbarayan, Sreevidya; Correa, Mark; Lo, Margaret C.; Suman, Amitabh; Cusi, Kenneth

doi:10.1016/j.jhep.2014.08.040

Cited by 100 publications

(77 citation statements)

References 38 publications

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“…For example, Li et al [15] found no association between the presence of ultrasonography quantified NAFLD and vitamin D status in 1,248 Chinese participants. More recently, Bril et al [14] assessed for associations between vitamin D deficiency and liver fat, in addition to the severity of NASH in 239 participants. Using magnetic resonance imaging and proton spectroscopy, the authors segregated patients based on their vitamin D status.…”

Section: Discussionmentioning

confidence: 99%

“…25 No 2: 175-181 peroxisome proliferator-activated receptor gamma (PPAR-γ) [12,13]. Although not all [14,15], many observational studies report associations between vitamin D deficiency and hepatic steatosis [12,16], the aggregate effect of which has been illustrated in a meta-analysis [17] confirming the presence of decreased serum 25-hydroxyvitamin D concentrations in such patients. Specifically, they were 26% more likely than healthy controls to be vitamin D deficient.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Short-Term Vitamin D Correction on Hepatic Steatosis as Quantified by Controlled Attenuation Parameter (CAP)

Papapostoli

Lammert

Stokes

2016

JGLD

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Introduction: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries. A meta-analysis has confirmed decreased serum 25-hydroxyvitamin D levels in NAFLD patients. This intervention study investigates whether vitamin D correction ameliorates hepatic steatosis. Methods: We prospectively recruited 40 patients from an outpatient liver clinic with vitamin D deficiency (serum 25-hydroxyvitamin D < 20 ng/ml). Controlled attenuation parameter (CAP) during transient elastography quantified hepatic steatosis. Patients with significant liver fat accumulation were included, which was defined by a CAP value ≥ 280 dB/m. Patients received 20,000 IU vitamin D/week for six months, while vitamin D status, liver function tests (LFTs), CAP and body composition were monitored. Results: The cohort comprised 47.5% women (age 54.9 ± 12.1 years; BMI 29.5 ± 3.0 kg/m2). Mean serum vitamin D level was 11.8 ± 4.8 ng/ml. CAP decreased significantly from baseline (330 ± 32 vs. 307 ± 41 dB/m) during supplementation (P = 0.007). A mean CAP reduction relative to baseline was demonstrated at four weeks and three and six months: -5.3 ± 13.8%; -6.0 ± 14.6% and -6.4 ± 13.0%, respectively. During these time points, restoration of serum vitamin D levels was observed (34.6 ± 12.9, 36.3 ± 10.2, 34.8 ± 9.8 ng/ml; P < 0.0001). Liver function tests and body composition remained unchanged. Conclusions: Hepatic steatosis, as assessed by CAP, significantly improves after only 4 weeks of vitamin D correction. Hepatic steatosis is a dynamic process, that can be monitored in the short-term using such non-invasive methods. Abbreviations: ALT: alanine aminotransferase; ANOVA: analysis of variance; AP: alkaline phosphatase; AST: aspartate aminotransferase; CAP: controlled attenuation parameter; CRP: C-reactive protein; FFA: free fatty acids; γ-GT: gamma-glutamyl transpeptidase; ITT: intention-to-treat; LFT: liver function test; LSM: liver stiffness measurement; NAFLD: non-alcoholic fatty liver disease; PPAR-γ: peroxisome proliferator-activated receptor gamma; PP: per protocol; PTH: parathyroid hormone; VDR: vitamin D receptor

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of Short-Term Vitamin D Correction on Hepatic Steatosis as Quantified by Controlled Attenuation Parameter (CAP)

Papapostoli

Lammert

Stokes

2016

JGLD

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“…While production of 1,25(OH) 2 D is tightly regulated to maintain calcium balance [12], more recently, it was suggested that 1,25(OH) 2 D has independent effects on features of the metabolic syndrome [13]. Clinical data, however, have been scarce and inconsistent: some studies reported an association between reduced 25(OH)D and insulin resistance in various populations [2,5,8], whereas others reported no such associations [14,15]. To date, no studies have investigated the relationship between circulating concentrations of the active 1,25(OH) 2 D metabolite and direct measures of glucose metabolism and insulin action in humans.…”

Section: Introductionmentioning

confidence: 99%

The vitamin D metabolites 25(OH)D and 1,25(OH)2D are not related to either glucose metabolism or insulin action in obese women

Horst

Versteeg

Gilijamse

et al. 2016

Diabetes & Metabolism

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“…On the contrary, Patel et al [9] found no association between vitamin D levels and the histopathological grade of liver steatosis. Similarly, Bril et al [8] observed that serum 25(OH)D concentrations were not related to fat accumulation in the liver, as measured by magnetic resonance spectroscopy.…”

Section: Discussionmentioning

confidence: 89%

“…We observed this effect in humans, which resulted in modest yet significant improvements in controlled attenuation parameter (CAP) values, and hence a reduction in the degree of liver steatosis after only 4 weeks of vitamin D therapy [3]. On the other hand, several observational studies reported a lack of association between vitamin D and fatty liver disease in humans [8, 9]. …”

Section: Introductionmentioning

confidence: 99%

Effects of Gene Variants Controlling Vitamin D Metabolism and Serum Levels on Hepatic Steatosis

Jamka¹,

Arslanow

Bohner

et al. 2018

Digestion

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Background/Aims: Common genetic variations in vitamin D metabolism are associated with liver stiffness. Whether these genes are implicated in hepatic steatosis remains unclear. Here we aimed to analyse the association of common vitamin D pathway gene variants with liver steatosis. Methods: Liver steatosis was assessed non-invasively in 241 patients with chronic liver conditions by controlled attenuation parameter (CAP). The following polymorphisms were genotyped using TaqMan assays: group-specific component (GC) rs7041, 7-dehydrocholesterol reductase (DHCR7) rs12785878, cytochrome P450 2R1 (CYP2R1) rs10741657, vitamin D receptor (VDR) rs7974353. Chemiluminescence immunoassay determined serum 25-hydroxyvitamin D (25(OH) D) concentrations. Results: Vitamin D deficiency (defined by 25(OH)D concentrations <20 ng/mL) occurred in 66% of patients. Median CAP was 296 (100–400) dB/m. Patients with advanced steatosis (CAP ≥280 dB/m) had significantly (p = 0.033) lower 25(OH)D levels as compared to patients with CAP <280 dB/m. Moreover, the rare allele [T] in GC rs7041 was significantly (p = 0.018) associated with higher 25(OH)D levels in patients with CAP <280 dB/m. However, GC, DHCR7, CYP2R1, and VDR polymorphisms were not related to liver steatosis and obesity traits. Conclusions: Higher CAP values are associated with low serum 25(OH)D concentrations but not with common vitamin D pathway gene variants.

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Relationship of vitamin D with insulin resistance and disease severity in non-alcoholic steatohepatitis

Cited by 100 publications

References 38 publications

Effect of Short-Term Vitamin D Correction on Hepatic Steatosis as Quantified by Controlled Attenuation Parameter (CAP)

Effect of Short-Term Vitamin D Correction on Hepatic Steatosis as Quantified by Controlled Attenuation Parameter (CAP)

The vitamin D metabolites 25(OH)D and 1,25(OH)2D are not related to either glucose metabolism or insulin action in obese women

Effects of Gene Variants Controlling Vitamin D Metabolism and Serum Levels on Hepatic Steatosis

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