LncOb rs10487505 variant is associated with leptin levels in pediatric non-alcoholic fatty liver disease.

BACKGROUND: Low and high leptin levels are associated with non-alcoholic fatty liver disease (NAFLD). The LncOb rs10487505 variant has been associated with body mass index (BMI), and the C allele was reported as leptin-lowering. We evaluated the association of rs10487505 with leptin levels, liver histology, and surgery-induced weight loss in youths with NAFLD. METHODS: One-hundred five obese youths with NAFLD, of whom 19 undergoing laparoscopic sleeve gastrectomy (LSG), were analyzed for rs10487505 and leptin circulating levels. RESULTS: The G allele frequency was lower in youths with NAFLD than in controls (p = 0.049). No difference was found in anthropometrics, biochemistry and histology between G allele carriers and CC homozygotes, except for leptin levels (p = 0.016). Leptin correlated with body weight, BMI, BMI-z score, waist circumference, insulin resistance/sensitivity, and triglycerides (p ≤ 0.01). A multivariable regression model including body weight and homeostasis model assessment of insulin resistance was a good predictor of plasma leptin (R2 = 0.45), and the addition of genotype to the model increased the R2 to 0.50. Following LSG, leptin levels and body weight were more reduced in G allele carriers (p < 0.05). CONCLUSIONS: LncOb rs10487505 variant was associated with pediatric NAFLD and high leptin levels, and with weight and leptin reduction after LSG in youths. IMPACT: The interplay of environment, genetics and epigenetics is crucial inflating the risk of non-alcoholic fatty liver disease (NAFLD). Several long non-coding RNA (LncRNAs) are found associated with NAFLD pathogenesis. Here, we evaluated the impact of the genetic variant rs10487505 in LncOb which is involved in the regulation of leptin gene expression. The LncOb rs10487505 is associated with increased levels of leptin, but not with liver histology, in youths with NAFLD. The LncOb rs10487505 was also associated with the significant decrease of leptin and body weight after bariatric surgery.

The Contribution of the Adipose Tissue-Liver Axis in Pediatric Patients with Nonalcoholic Fatty Liver Disease after Laparoscopic Sleeve Gastrectomy.

OBJECTIVE: To evaluate the histopathologic modifications in liver and visceral adipose tissue (VAT), and to correlate these changes with clinical measures, adipokine production, and proinflammatory cytokines in a population of adolescents with obesity with nonalcoholic fatty liver disease (NAFLD) who underwent laparoscopic sleeve gastrectomy (LSG). STUDY DESIGN: Twenty adolescents with obesity who underwent LSG and with biopsy-proven NAFLD were included. Patients underwent clinical evaluation and blood tests at baseline and 1 year after the surgical procedure. Liver and VAT specimens were processed for routine histology, immunohistochemistry, and immunofluorescence. RESULTS: In adolescents with obesity and NAFLD, hepatic histologic alterations were uncorrelated with VAT inflammation. LSG induced in both liver and VAT tissue histopathology amelioration and macrophage profile modification that were correlated with body mass index and improvement in insulin resistance. The adipokine profile in liver and VAT was associated with weight loss and histologic improvement after LSG. Serum proinflammatory cytokines were correlated with liver and VAT histopathology and IL-1ß and IL-6 levels were independently predicted by liver necroinflammatory grade. CONCLUSIONS: This study suggests a unique adipose tissue/fatty liver crosstalk in pediatric patients. LSG induces a similar pattern of histologic improvement in the liver and in VAT. Besides VAT, our results strengthen the role of the liver in adipocytokine production and its contribution to systemic inflammation in pediatric patients with NAFLD.

Elevated Hemoglobin Level Is Associated With Advanced Fibrosis in Pediatric Nonalcoholic Fatty Liver Disease.

OBJECTIVES: Hemoglobin (Hb) and red blood cell distribution width (RDW) have been reported to be a risk marker of metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). No study exists on pediatric populations. We aimed to determine the association between hematological parameters, and the severity of disease in children with biopsy-proven NAFLD. METHODS: A total of 117 children (85 boys, mean age 12 years) with ultrasound evidence of NAFLD undergoing liver biopsy for diagnosis of nonalcoholic steatohepatitis (NASH), were prospectively enrolled between January 2011 and May 2013 in the setting of a tertiary care center. Children were screened for routine hematological and metabolic parameters, and causes of liver steatosis other than nonalcoholic were excluded, before liver biopsy was performed. RESULTS: A total of 41 NAFLD (boys 29, mean age 11.2 years) and 76 NASH (boys 56, mean age 12.8 years) children were studied. Alanine transaminase levels were significantly higher in NASH group compared with NAFLD group (P = 0.05), and homeostatic model assessment of insulin resistance and triglycerides levels (P = 0.03 and 0.02, respectively). Regarding hematological components: red cell count, Hb, hematocrit, and RDW values were all significantly higher in NASH group compared with NAFLD group (P < 0.05 for each parameter). CONCLUSIONS: Children with NASH were more likely to have high levels of RDW compared to those with steatosis only. Moreover, NASH was associated with higher red cell count, Hb, and hematocrit. If confirmed in future follow-up studies, hematological parameters may be introduced in algorithms for NASH risk prediction.

Changes in Total Homocysteine and Glutathione Levels After Laparoscopic Sleeve Gastrectomy in Children with Metabolic-Associated Fatty Liver Disease.

PURPOSE: Paediatric obesity is a well-known risk factor for metabolic-associated fatty liver disease (MAFLD). The aim of this study was to evaluate the effects of laparoscopic sleeve gastrectomy (LSG) on the levels of total homocysteine (tHcy) and total glutathione (tGSH) plasma levels in children with MAFLD. MATERIAL AND METHODS: Twenty-four children with severe obesity who underwent LSG were included in the study. The metabolic parameters, systemic inflammatory markers, one-carbon metabolism products, ultrasound and histological improvement were evaluated at baseline (T0M) and after 12 months from LSG (T12M). RESULTS: The patients exhibited a significant amelioration of several metabolic parameters at T12M. A significant reduction of steatosis was observed at ultrasound (from 72.7% of moderate-severe grade to 0% severe steatosis), accompanied by a statistically significant improvement of ballooning, portal and lobular inflammation and fibrosis. A statistically significant decrease of tumour necrosis factor circulating levels was also observed (T0M median = 290.3, IQR = 281.0-317.0 pg/mL; T12M median = 260.4, IQR = 240.0-279.0 pg/mL; p < 0.0001). After 12 months from LSG, a significant increase of mean plasma levels of tHcy(T0M mean = 15.7 ± 4.1 µmol/L; T12M mean = 21.1 ± 9.3 µmol/L; p = 0.0146) was also observed. The increase of tHcy showed no causal link with the improvement of MAFLD-related inflammatory, metabolic and histological pattern. CONCLUSION: LSG in children with obesity induces an improvement of MAFLD-related metabolic derangement and liver damage, but also a mild hyperhomocysteinemia that should be avoided to prevent cardiovascular risk.

The APOC3 T-455C and C-482T promoter region polymorphisms are not associated with the severity of liver damage independently of PNPLA3 I148M genotype in patients with nonalcoholic fatty liver.

BACKGROUND & AIMS: The T-455C and C-482T APOC3 promoter region polymorphisms (SNPs) have recently been reported to predispose to dyslipidemia, insulin resistance, and nonalcoholic fatty liver disease (NAFLD) in Indian subjects, but the association with liver damage has not been evaluated so far. The aim was to assess the association between APOC3 SNPs and liver damage in Caucasian patients. METHODS: We considered 437 Italian patients with histological diagnosis of NAFLD (including 137 children, 120 morbid obese) and 316 healthy controls, 71 Italian family trios, and 321 patients from the UK. APOC3 SNPs were determined by sequencing, allele-specific oligonucleotide probes and PCR-restriction fragment length polymorphism analysis, hepatic APOC3 mRNA levels by real-time PCR. RESULTS: APOC3 SNPs were not associated with NAFLD in Italian subjects, although a borderline significance for the transmission of the -455T allele was observed in the family study. Homozygosity for the APOC3 wild-type genotype (APOC3 WT) was associated with a more favorable lipid profile in control subjects, and consistently with lower hepatic APOC3 mRNA levels in obese patients without diabetes. However, APOC3 SNPs, alone or in combination, were not associated with insulin resistance, altered lipid levels, liver enzymes, and with liver damage (severity of steatosis, nonalcoholic steatohepatitis, and moderate/severe fibrosis) in Italian as well as in UK patients, and in the whole cohort. Stratification for the I148M PNPLA3 mutation, associated with the susceptibility to NASH, did not alter the results. CONCLUSIONS: APOC3 genotype is not associated with progressive liver damage in Caucasian patients with NAFLD.

I148M patatin-like phospholipase domain-containing 3 gene variant and severity of pediatric nonalcoholic fatty liver disease.

UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease in children. Genetic variability, which is a main player in NAFLD, is especially characterized by polymorphisms in genes involved in the development and progression of the disease to nonalcoholic steatohepatitis (NASH). Recently, the rs738409 C>G adiponutrin/patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphism, which encodes the I148M protein variant in the catalytic domain, has been associated with severe steatosis, NASH, and liver fibrosis in adults. In this study, we investigated the association between the rs738409 PNPLA3 gene polymorphism and NAFLD in 149 consecutive children and adolescents (age = 6-13 years) with biopsy-proven NAFLD. We analyzed the rs738409 polymorphism by a 5'-nuclease TaqMan assay and assessed its association with NASH: 41% of the subjects with NAFLD showed heterozygosity and 15% showed homozygosity for the at-risk G allele. The rs738409 genotype did not influence the body mass, adiposity, lipid levels, or insulin resistance and was not associated with alanine aminotransferase levels. Interestingly, the rs738409 G allele was strongly associated with the severity of steatosis (P < 0.0001), the presence of NASH (P < 0.0001), hepatocellular ballooning (P < 0.0001), lobular inflammation (P < 0.0001), and the presence of fibrosis (P = 0.01) independently of confounders. Individuals carrying two minor G alleles almost always had severe steatosis and NASH, heterozygotes were at intermediate risk, and patients negative for G alleles had milder and often uncomplicated steatosis. CONCLUSION: The PNPLA3 rs738409 polymorphism is associated with steatosis severity, hepatocellular ballooning, lobular inflammation, and perivenular fibrosis in pediatric NAFLD.

Insulin dynamics of breast- or formula-fed overweight and obese children.

OBJECTIVE: The aim of the present study was to evaluate the association between the type of early feeding and indices of insulin metabolism in 8-year-old overweight and obese children. METHODS: The sample included 350 overweight (body mass index [BMI] ≥1.036 standard deviation score [SDS]) and obese (BMI ≥1.645 SDS) children and 33 normal-weight control subjects who had been exclusively breast-fed or formula-fed for 4 months or longer. Parameters of insulin sensitivity and secretion were derived from 120-minute oral glucose tolerance tests. RESULTS: Overweight and obese formula-fed children (N = 165) were more insulin resistant than breast-fed individuals (N = 185; Whole-Body Insulin Sensitivity Index 5.1 ± 2.3 vs 6.6 ± 2; p < 0.0001) despite having the same degree of obesity (BMI z-score 1.8 ± 0.4 vs 1.7 ± 0.4 SDS; p = 0.5). They compensated for enhanced insulin resistance by augmenting insulin secretion (Insulinogenic Index 6.8 ± 3.6 vs 5.2 ± 2.5 µIU/mL × mg/mL(-1); p < 0.0001). Thus, they presented with a disposition index similar to that of breast-fed children (34.6 ± 15 vs 30.8 ± 19.2; p = 0.4), Formula feeding was associated with greater catch-up growth in the first month (odds ratio 2.49, 95% confidence interval 1.97 to 3.01; p < 0.0001) and between months 6 and 12 of life (odds ratio 4.62, 95% confidence interval 3.58 to 5.67; p < 0.0001). CONCLUSIONS: In comparison with breast-feeding, formula feeding seems to be associated with reduced insulin sensitivity and increased insulin secretion in overweight and obese children.

Antioxidant activity of Hydroxytyrosol and Vitamin E reduces systemic inflammation in children with paediatric NAFLD.

BACKGROUND: The rise in paediatric non-alcoholic fatty liver disease (NAFLD) is particularly alarming. We recently reported that Hydroxytyrosol (HXT) and Vitamin E (VitE) may improve oxidative stress, insulin resistance, and steatosis in children with biopsy-proven NAFLD. AIM: Here, we investigated if HXT+VitE may reduce systemic inflammation in the above-mentioned patients. METHODS: This study analysed the plasma levels of IL (interleukin)-6, IL-1ß, IL-10, tumour necrosis factor (TNF)-α, 4­hydroxy-2-nonenal (4-HNE) and 8-hydroxy-2'deoxyguanosine (8-OHdG) in children enrolled in the HXT+VitE trial (ClinicalTrials.gov, NCT02842567). RESULTS: Changes in markers of systemic inflammation were found in both placebo (Pla) and HXT+VitE. In particular, after four months, the levels of IL-1ß and TNF-α were reduced in both groups, while IL-6 decreased, and IL-10 increased significantly only in the group treated with HXT+VitE. Children treated with HXT+VitE showed a significant decrease of 4-HNE and 8-OHdG that correlated with the improvement of triglyceride levels. Noticeably, only the 8-OHdG decrease correlated with steatosis amelioration and with the increase of IL-10 levels. CONCLUSION: The treatment with HXT and VitE reduced the NAFLD-related systemic inflammation in children, mainly by an increase of IL-10 circulating levels that occurred in response to DNA damage recovery, ultimately improving steatosis and hypertriglyceridemia.

Variations in exhaled nitric oxide in children with asthma during a 1-week stay in a mountain village sanatorium.

Knowing about spontaneous variations in the fractional concentration of exhaled nitric oxide (FE(NO)) could improve monitoring of airway inflammation in asthmatic children. We aimed to assess FE(NO) variations (expiratory flow 50 mL/sec) in subjects maintained in similar environmental conditions. We tested spirometry and FE(NO) in symptom-free asthmatic children (9 corticosteroid-naive, 8 corticosteroid-treated) during a 1-week stay in a countryside sanatorium and in their healthy relatives (n = 12) staying in the immediate neighborhood on summer holiday (total 29 children, M/F:14/15, 5.8-16.8 yrs). Testing sessions were repeated every 12 hours (8:00 am, 8:00 pm) for 2 days and again on day 7. Measurements were defined as reproducible when they agreed with an intraclass correlation coefficient (ICC) above 0.60; deviation from mean differences was assessed by the coefficient of repeatability (CR = 2 SD). Lung function remained constant throughout the week in all groups. Baseline FE(NO) levels in corticosteroid-naive asthmatic children tended to decrease at the end of the week (from 13.9 ppb, 95% CI 12.2-19.1 to 9.2 ppb, 95% CI 5.8-15.9, p = 0.057). No differences were found between nocturnal and diurnal FE(NO). Within-session reproducibility for two FE(NO) measurements was high (ICC 0.99 in all groups and CR, 0.9 to 1.3 ppb). Between-session FE(NO) reproducibility at 12 hours and 24 hours was still high for each group but decreased markedly after 6 days in corticosteroid-naive asthmatic children (ICC 0.79 and CR 9.6 ppb at 24 hours vs. ICC 0.13 and CR 20.8 ppb after 6 days), whereas it decreased slightly in corticosteroid-treated asthmatics (from ICC 0.89 and CR 3.1 ppb to ICC 0.88 and CR 3.0 ppb) and healthy children (from ICC 0.79 and CR 4.8 ppb to ICC 0.65 and CR 5.7 ppb). In conclusion, in healthy subjects and in asthmatic children receiving therapy with inhaled corticosteroids (but not in corticosteroid-naive subjects), FE(NO) measurements are reproducible across a week.

Good adherence to the Mediterranean diet reduces the risk for NASH and diabetes in pediatric patients with obesity: The results of an Italian Study.

OBJECTIVE: In the last decade, it was demonstrated that the Mediterranean diet (MD) represents an ideal diet for all age groups and has an important role in the prevention of metabolic and cardiovascular diseases, as well as nonalcoholic fatty liver disease (NAFLD). The aim of the present study was to analyze the association between adherence to the MD and NAFLD, with laboratory and histologic evaluation, in a group of children and adolescents with obesity. METHODS: We enrolled 243 patients with obesity referred to our department from March 2014 to November 2015. In all patients, we performed abdominal ultrasound and laboratory assays. In selected cases (100 patients) liver biopsy was performed. Level of adherence to the MD was evaluated by a clinical questionnaire, the Mediterranean Diet Quality Index for children and adolescents (KIDMED). RESULTS: The prevalence of low KIDMED score was significantly higher in patients with nonalcoholic steatohepatitis compared with other groups; poor adherence to the MD correlated with liver damage, the NAFLD activity score >5, and grade 2 fibrosis. Moreover, in patients with poor adherence to the MD, higher values of C-reactive protein, fasting insulin, homeostatic model assessment of insulin resistance, and homeostatic model assessment of ß cell function were observed. CONCLUSION: The MD could be a safe and inexpensive therapeutic option for children with obesity and NAFLD.

The Obalon swallowable intragastric balloon in pediatric and adolescent morbid obesity.

Background and study aims Incidence of morbid obesity has grown dramatically in the last half century and this phenomenon affects with particular severity the pediatric population. Dietary restrictions and careful programs to improve lifestyle are often ineffective to manage this particular group of patients, due to poor compliance typical of the adolescence. The aim of this study was to evaluate the effectiveness of a new intragastric balloon for treatment of morbidly obese children. Patients and methods A new swallowable intragastric balloon (Obalon) has been used for the first time in 17 obese children in order to assess its safety and effectiveness in terms of reduction in excess weight. In 9 of 17 children a second balloon was placed 30 to 40 days after the first insertion. All devices were endoscopically removed after a mean time of 18 weeks. Results In the group of 16 patients who completed the study (1 patient still under treatment) mean weight decreased from 95.8 ±â€Š18.4 Kg to 83.6 ±â€Š27.1 (P < 0.05). Mean body mass index (BMI) decreased from 35.27± 5.89 (range 30.4 - 48) to 32.25 ±â€Š7.1 (range 23.5 - 45.7) (P > 0.05); mean excess weight, calculated according to Cole's curves for pediatric populations, decreased from 36.2 ±â€Š15.9 to 29.4 ±â€Š18.3 Kg (P = 0.14), with an %EWL of 20.1 ±â€Š9.8 (range 2.3 - 35.1). Waist circumference decreased from 109 ±â€Š12.3 cm to 99 ±â€Š10.5 cm (P < 0.05). Conclusions Obalon can be administered easily without complications, inducing an appreciable weight loss with a statistically significant reduction in BMI and an improvement in associated comorbidities.

Pediatric liver diseases: current challenges and future perspectives.

Chronic liver diseases in children represent a rising problem with significant effects on public health. In fact, several pediatric liver diseases are precursors of adult chronic hepatopathies, cirrhosis and hepatocellular carcinoma. The prevalence of liver diseases in children is unknown. In the USA, every year, 15,000 children are hospitalized for liver diseases, but these disorders continue to be under-recognized or diagnosed late. The main reason is due to the frequent absence of symptoms in the vast majority of liver diseases, especially in the early stages. In the last few decades several advances have been made in understanding the pathogenesis of liver diseases, permitting the discovery of new therapeutic targets to treat liver diseases, thus improving the natural history of these disorders. In this article we discuss the most recent advances in the understanding of the pathogenesis, diagnosis and treatment of the most frequent pediatric liver diseases.

Pulse transit time as a measure of inspiratory effort in children.

STUDY OBJECTIVES: The current criterion standard for measuring inspiratory effort, esophageal manometry, is an invasive procedure that young patients find intolerable. Inspiratory effort can also be assessed noninvasively by measuring the pulse transit time (PTT). PTT is the time the pulse wave (PW) takes to travel between two arterial sites (normally heart to finger). The speed at which the PW travels is directly proportional to arterial BP. When BP rises, PTT shortens. Conversely, when BP falls, PTT lengthens. In this study, we investigated PTT as a measure for evaluating inspiratory effort in children. PARTICIPANTS: We studied 15 healthy children (age range, 5 to 12 years; mean age [+/- SD], 8.3 +/- 2.74; 9 male children) selected from patients referred to our pediatric center for routine assessment. MEASUREMENTS AND RESULTS: We assessed changes in the PTT during breathing against known resistances in awake children. Resistance was applied to the nose and mouth with a modified, two-way, nonrebreathing facemask. Our data show a good correlation between the induced inspiratory effort and the amplitude of PTT variations. CONCLUSIONS: PTT should be a useful method for quantifying changes in inspiratory effort due to augmented upper airway resistance in awake children.

Non-alcoholic fatty liver and metabolic syndrome in children: a vicious circle.

During the last decade, paediatricians have observed a dramatic increase of non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) in children. Furthermore, several lines of evidence have reported that a large part of children with NAFLD presents one or more traits of MS making plausible that, in the coming years, these subjects may present a rapid course of disease towards more severe cirrhosis and cardiovascular disease. Genetic susceptibility and the pressure of intrauterine environment and lifestyle are all crucial to activate molecular machinery that leads to development of NAFLD and MS in childhood. In this scenario, central obesity and consequent adipose tissue inflammation are critical to promote both MS-associated metabolic dysfunctions and NAFLD-related hepatic damage. An excessive dietary intake may in fact cause a specific lipid partitioning and induce metabolic stressors, which in turn promote insulin resistance and the release of several circulating factors. These molecules, on the one hand, trigger steatosis and the inflammatory response that characterize liver damage in NAFLD, and on the other hand contribute to the onset of other features of MS. This review provides an overview of current genetic, pathogenetic and clinical evidence of the vicious circle created by NAFLD and MS in children.

Celiac disease in pediatric patients with autoimmune hepatitis: etiology, diagnosis, and management.

Celiac disease (CD) is defined as a permanent intolerance to ingested wheat gliadins and other cereal prolamins, occurring in genetically susceptible people. Persistent elevation of serum aminotransferase activity is expression of liver damage related to CD, which occurs in two distinctive forms. The most frequent is a mild asymptomatic liver injury, with a moderate increase of serum aminotransferase activities and a mild inflammatory portal and lobular infiltrate on liver biopsy (celiac hepatitis), reversible on a gluten-free diet (GFD). More rarely, severe and progressive inflammatory liver damage, induced by an autoimmune process and identified as autoimmune hepatitis (AIH), can develop and it is generally unaffected by gluten withdrawal. Surveys that included only pediatric patients report a wide range of prevalence of CD in AIH of 11.5-46% (mean 21.5%). CD and AIH share selected combinations of genes coding for class II human leukocyte antigens, which could explain their coexistence. Increased intestinal permeability and circulation of anti-tissue transglutaminase (tTG) have also been considered as further potential causes of liver damage in CD patients. tTG in the liver and in other extraintestinal tissues could modify other external- or self-antigens and generate different neo-antigens, which are responsible for liver injury in patients with CD. Patients with AIH represent a population at high risk for developing CD; screening for CD should be integrated into the diagnostic routine of all patients with AIH, with or without gastrointestinal manifestations, before starting immunosuppressive treatments. The only currently available treatment for CD is the GFD and the supportive nutritional care for iron, calcium, and vitamin deficiencies. Due to the difficulties of a GFD, in the past decade researchers have become increasingly interested in therapeutic alternatives to continuous or intermittent use of a GFD in patients with CD. Interventions addressed to correct the defect in the intestinal barrier are currently at the most advanced stage of clinical trials. The impact of a GFD on the outcome of AIH is not clear but it seems to be ineffective in the treatment of AIH. The early detection and treatment of CD, however, may prevent progression to end-stage liver failure.

Cannabinoid receptor type 2 functional variant influences liver damage in children with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of disease ranging from simple steatosis to inflammatory steatohepatitis (NASH) with different degrees of fibrosis that can ultimately progress to cirrhosis. Accumulating evidence suggests the involvement of the endocannabinoid-system in liver disease and related complications. In particular, hepatoprotective properties for Cannabinoid Receptor type 2 (CB2) have been shown both through experimental murine models of liver injury and association study between a CB2 functional variant, Q63R, and liver enzymes in Italian obese children with steatosis.Here, in order to clarify the role of CB2 in severity of childhood NAFLD, we have investigated the association of the CB2 Q63R variant, with histological parameters of liver disease severity in 118 Italian children with histologically-proven NAFLD.CB2 Q63R genotype was assigned performing a TaqMan assay and a general linear model analysis was used to evaluate the association between the polymorphism and the histological parameters of liver damage.We have found that whereas CB2 Q63R variant is not associated with steatosis or fibrosis, it is associated with the severity of the inflammation (p = 0.002) and the presence of NASH (p = 0.02).Our findings suggest a critical role for CB2 Q63R variant in modulating hepatic inflammation state in obese children and in the consequent increased predisposition of these patients to liver damage.

Expert opinion on current therapies for nonalcoholic fatty liver disease.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming one of most common liver diseases in industrialized countries owing to the increasing prevalence of obesity and being overweight. Until now, loss of weight and physical activity have represented the cornerstone of treatment, but they are very difficult to achieve and to maintain. Therefore, new treatments based on pathogenetic mechanisms leading to NAFLD are under evaluation to establish an effective pharmacological therapy for this disorder. AREAS COVERED: An overview of current therapeutic interventions to treat NAFLD is given. This review provides evidence of the efficacy of natural and pharmacological agents used so far in the treatment of both adult and pediatric NAFLD, on the basis of clinical trials published in the last 10 years. EXPERT OPINION: In the last 10 years, many pharmacological agents on the basis of the pathogenetic mechanism of NAFLD have been attempted, but so far guidelines for the management of NAFLD are lacking. We believe that the advance in the understanding of pathogenesis and factors involved in the progression of the disease may disclose the way to defining new, solid, therapeutic strategies. A multidisciplinary approach considering the risk factors and comorbidities of fatty liver will represent in the future a successful therapeutic strategy for NAFLD.

Successful tenofovir treatment for fulminant hepatitis B infection in an infant.

Fulminant hepatic failure is defined by the presence of severe impairment of liver function, with or without encephalopathy, in patients with no underlying chronic liver disease. We report the case of a 4-month-old infant who developed fulminant hepatitis B infection and recovered concomitant with tenofovir therapy without liver transplantation.

A rare condition of Hand-Schüller-Christian disease.

The authors present the clinical case of a 61-year-old patient with Hand-Schüller-Christian disease associated with multisystemic involvement. The onset of such puzzling symptoms and the extremely rarity of this disease in a patient of such advanced age resulted in a delayed diagnosis and subsequently delayed treatment of the patient.