Nonalcoholic fatty liver disease (NAFLD) is emerging as the most common chronic liver disease, and is characterized by a wide spectrum of fat-liver disorders that can result in severe liver disease and cirrhosis. Inflammation and oxidative stress are the major risk factors involved in the pathogenesis of NAFLD. Currently, there is no consensus concerning the pharmacological treatment of NAFLD. However, lifestyle interventions based on exercise and a balanced diet for quality and quantity, are considered the cornerstone of NAFLD management. Mediterranean diet (MD), rich in polyunsaturated fats, polyphenols, vitamins and carotenoids, with their anti-inflammatory and anti-oxidant effects, has been suggested to be effective in preventing cardiovascular risk factors. In adults, MD has also been demonstrated to be efficacious in reducing the risk of metabolic syndrome. However, few studies are available on the effects of the MD in both adult and pediatric subjects with NAFLD. Thus, the aims of the present narrative review are to analyze the current clinical evidence on the impact of MD in patients with NAFLD, and to summarize the main mechanisms of action of MD components on this condition.

We conducted a double-blind trial of high-dose parenteral 6-methylprednisolone (MP) and placebo on 23 patients with acute MS. After the double-blind trial, the patients were given corticosteroids in gradually decreasing doses. The frequency of improvement was significantly higher and the bout duration significantly lower in the MP group than in the placebo group. The first signs of improvement (3 to 6 days after starting MP) were associated with a marked decrease in the rate of CNS IgG synthesis, but IgG CSF oligoclonal bands did not change. CNS IgG production slowly returned toward baseline despite progressive clinical improvement.

Due to the epidemic of obesity across the world, nonalcoholic fatty liver disease (NAFLD) has become one of the most prevalent chronic liver disorders in children and adolescents. NAFLD comprises a spectrum of fat-associated liver conditions that can result in end-stage liver disease and the need for liver transplantation. Simple steatosis, or fatty liver, occurs early in NAFLD and may progress to nonalcoholic steatohepatitis, fibrosis and cirrhosis with increased risk of hepatocellular carcinoma. The mechanism of the liver injury in NAFLD is currently thought to be a “multiple-hit process” where the first “hit” is an increase in liver fat, followed by multiple additional factors that trigger the inflammatory activity. At the onset of disease, NAFLD is characterized by hepatic triglyceride accumulation and insulin resistance. Liver fat accumulation is associated with increased lipotoxicity from high levels of free fatty acids, free cholesterol and other lipid metabolites. As a consequence, mitochondrial dysfunction with oxidative stress and production of reactive oxygen species and endoplasmic reticulum stress-associated mechanisms, are activated. The present review focuses on the relationship between intra-cellular lipid accumulation and insulin resistance, as well as on lipid and lipoprotein metabolism in NAFLD.

Novel lipid-lowering agents have potential to improve the performance of LA, but more evidence is needed. The Multidisciplinary International Group for Hemapheresis TherapY and Metabolic DIsturbances Contrast scientific society aims to establish an international registry of clinical experience on LA combination therapy to expand the evidence on this treatment in individuals at high cardiovascular disease risk.

ObjectivesTo comprehensively explore metabolic and genetic contributors to liver fat accumulation in overweight/obese children.MethodsTwo hundred thirty Italian children with obesity were investigated for metabolic parameters and genotyped for PNPLA3, TM6SF2, GCKR, and MBOAT7 gene variants. Percentage hepatic fat content (HFF%) was measured by nuclear magnetic resonance.ResultsHFF% was positively related with BMI, HOMAIR, metabolic syndrome, ALT, AST, γGT, and albumin. Carriers of [G] allele in PNPLA3, [T] allele in GCKR and [T] allele in TM6SF2 genes had significantly higher hepatic fat content than wild-type carriers. HFF% was explained for 8.7% by metabolic and for 16.1% by genetic factors and, a model including age, gender, BMI, HOMAIR, PNPLA3, GCKR, and TM6SF2 variants was the best predictor of HFF%, explaining 24.8% of its variation (P < 0.001). A weighted-genetic risk score combining PNPLA3, GCKR, and TM6SF2 risk alleles was associated with almost eightfold higher risk of NAFLD.ConclusionsOur data highlighted the predominant role of genetic factors in determining the amount of liver fat content in children with obesity.

Vigabatrin is considered the drug of choice for infantile spasms and simple and complex partial epilepsy in childhood. Its mechanism of action relies on the irreversible inhibition of gamma-aminobutyric acid (GABA) transaminase. Since June 1997 several articles have been published reporting visual field constriction in adult patients on vigabatrin therapy. Recently, 7 pediatric patients, 1 on vigabatrin monotherapy and 6 on add-on therapy with visual field constriction have been described. We have observed 30 pediatric patients with epilepsy (14 boys and 16 girls), ages ranging from 4 to 20 years (mean: 11 years and 2 months) treated with vigabatrin for infantile spasms, simple and complex partial epilepsy, who had never complained of ophthalmologic disturbances. Twenty-one patients underwent complete routine ophthalmologic examination (fundus oculi, visual acuity, intraocular pressure, and visual field tests); 9 children (<6 years old) underwent only fundus examination, because collaboration was lacking. We report on 4 children showing constriction of visual field, prevailing in nasal hemifield. In 1 child, visual abnormalities were stable even 10 months after vigabatrin discontinuation, while in another a greater improvement was observed 5 months after discontinuation. The possible mechanisms have been discussed and the cone dysfunction, connected with GABA augmentation in the outer retina, has been outlined. We suggest a possible protocol to control visual abnormalities in epileptic children.

Background: Recent studies in adult non-elderly and elderly individuals have reported a link between nonalcoholic fatty liver disease (NAFLD) and sarcopenia. Nonetheless, whether this relationship would be found outside these populations it is still unknown. Hence, we evaluated the relationship between NAFLD and skeletal muscle mass in children and adolescents with overweight/obesity. Methods: Two-hundred and thirty-four overweight/obese youths were enrolled. NAFLD was diagnosed by ultrasononography, after exclusion of infectious and metabolic disorders. Forty of the patients with NAFLD had also liver biopsy. Total and regional lean body mass and total fat mass measurements were obtained by dual-energy X-ray absorptiometry. The relative muscle mass (RMM) was defined as the percent of muscle mass (kg) relative to the sum of muscle and fat (kg) mass. Appendicular skeletal muscle mass (ASM) was calculated by the sum of muscle masses of the four limbs (kg), and expressed as percent of body weight. Results: Subjects were stratified according to tertiles of RMM. The prevalence of abdominal obesity, dyslipidemia, insulin resistance, metabolic syndrome, NAFLD as well as biopsy-proven nonalcoholic steatohepatitis (NASH) was significantly increased in the lowest tertile of RMM. After controlling for age, sex and Tanner stage, children in the lowest tertile of RMM had an increased risk for NAFLD (OR= 2.80, 95% CI=1.57-5.02) compared to those in the other two tertiles. This association persisted after additional adjustments for clinical and metabolic variables. Similarly, the risk of NAFLD in the lowest tertile of ASM/weight index was significantly higher compared to those in the other two tertiles after adjustment for the above confounders. Conclusions: This is the first study to establish an independent association between low muscle mass and NAFLD/NASH in overweight/obese youths. Considering the worldwide increase of pediatric obesity, measurements of muscle mass may serve as useful method of identifying among obese children those at high metabolic risk who may need intensive lifestyle interventions to prevent NAFLD and its progression.

Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of kidney disease in adults and children. However, it is uncertain whether this association is influenced by major NAFLD susceptibility genes. In a sample of 230 overweight/obese children, 105 with NAFLD (hepatic fat fraction ≥5% by magnetic resonance imaging) and 125 without NAFLD, rs738409 in PNPLA3, rs58542926 in TM6SF2, rs1260326 in GCKR, and rs641738 in MBOAT7 were genotyped. Abnormal kidney function was defined as estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2 and/or the presence of microalbuminuria (24 h urinary albumin excretion between 30 and 300 mg). In comparison with children without NAFLD, those with NAFLD showed increased prevalence of reduced eGFR (13.3% vs. 1.6%; p < 0.001) and microalbuminuria (8.6% vs. 3.4%, p = 0.025). TM6SF2, GCKR, and MBOAT7 risk alleles did not show any impact on kidney function, while the PNPLA3 G allele was associated with lower eGFR, but only in children with NAFLD (p = 0.003). After adjustment for confounders, NAFLD (OR, 4.7; 95% CI, 1.5–14.8; padj = 0.007), but not the PNPLA3 gene variant, emerged as the main independent predictor of renal dysfunction. Overall, our findings suggest that NAFLD remains the main determinant of decline in kidney function in overweight/obese children, while the PNPLA3 rs738409 prosteatogenic variant has a small impact, if any.