Abstract
BackgroundThere are no licensed treatments for non alcoholic fatty liver disease (NAFLD) in adults or children. In NAFLD, several studies have shown a benefit of omega-3 fatty acid treatment on lipid profile, insulin-sensitivity and hepatic steatosis and it has also been suggested that Vitamin D treatment has potential antifibrotic properties in liver disease.Trial DesignTo date, however, there are no studies that have tested the combination of Docosahexanoic acid (DHA) and vitamin D treatment which may benefit the whole spectrum of disease in NAFLD. Our aim therefore, was to test the effect of daily DHA (500 mg) plus vitamin D (800 IU) treatment, in obese children with biopsy-proven NAFLD and vitamin D deficiency, in a randomized, double-blind placebo-controlled trial.MethodsThe 41/43 patients completed the study (18-treatment, 23-placebo). At 12 months: i) the main outcome was liver histology improvement, defined by NAS; ii) the secondary outcome was amelioration of metabolic parameters.ResultsDHA plus vitamin D treatment reduced the NAFLD Activity Score (NAS), in the treatment group (5.4 v1.92; p<0.001 for baseline versus end of study). There was no change in fibrosis score, but a reduction of the activation of hepatic stellate cells (HSC) and fibrillar collagen content was noted (3.51±1.66 v. 1.59±1.37; p = 0.003) in treatment group. Moreover, the triglycerides (174.5 vs. 102.15 mg/dl), ALT (40.25 vs. 24.5 UI/l) and HOMA-IR (4.59 vs. 3.42) were all decreased with treatment.ConclusionDHA plus vitamin D treatment improved insulin-resistance, lipid profile, ALT and NAS. There was also decreased HSC activation and collagen content with treatment.
Highlights
Following the epidemic of obesity and metabolic syndrome recorded in children and adolescents in the last couple of decades, nonalcoholic fatty liver disease (NAFLD) has become the main cause of chronic liver disease in these groups
There was no change in fibrosis score, but a reduction of the activation of hepatic stellate cells (HSC) and fibrillar collagen content was noted (3.51±1.66 v. 1.59±1.37; p = 0.003) in treatment group
Children were eligible for the study if they were between: 4 and 16 years of age, had a liver biopsy result consistent with a diagnosis of non alcoholic fatty liver disease (NAFLD)/NASH, and had decreased serum vitamin D levels (< 20 ng/ml), aminotransferases (ALT) levels
Summary
Following the epidemic of obesity and metabolic syndrome recorded in children and adolescents in the last couple of decades, nonalcoholic fatty liver disease (NAFLD) has become the main cause of chronic liver disease in these groups. The rate of progression of liver disease in NAFLD is slow with an estimated average of 7 years elapsing between the development of NASH with fibrosis in patients who had prior nonalcoholic fatty liver [5,6]. Fibrosis is characterized by an excessive deposition of extracellular matrix (ECM), with increases in total collagen content and in fibril-forming collagens (Type I, III and IV) [7]. These changes induce dysfunction and activation of the hepatic stellate cells (HSCs) with development and progression of fibrogenesis. In NAFLD, several studies have shown a benefit of omega-3 fatty acid treatment on lipid profile, insulin-sensitivity and hepatic steatosis and it has been suggested that Vitamin D treatment has potential antifibrotic properties in liver disease
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