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SummaryObjective The aim of this study was to evaluate the metabolic effects of fatty pancreas (nonalcoholic fatty pancreas disease -NAFPD) in a group of obese paediatric patients with nonalcoholic fatty liver disease (NAFLD). Methods We included 121 consecutive children with echographic evidence of hepatic steatosis. All patients underwent to abdominal ultrasound to evaluate pancreatic echogenic pattern. We divided the patients into two groups on the basis of the presence of fatty pancreas. In all patients liver function tests, lipid and gluco-insulinemic profile were evaluated. A selected subset of patients (67) underwent to liver biopsy. Results Of these 121 patients, 58 showed NAFPD and 63 patients exhibited a normal pancreatic echogenic pattern. No differences were found in age, transaminases serum levels, lipid profile and pancreatic enzymes between the two groups. The patients with NAFPD had a significantly higher z-BMI, fasting insulin, insulin resistance (HOMA-IR) and lower ISI respect to the group without fatty pancreas. The patients with fatty pancreas showed a more advanced form of liver disease, with higher values of fibrosis, ballooning and NAS score with respect to the group without NAFPD. Conclusions Our study demonstrated that NAFPD is a frequent condition in obese paediatric patients affected by NAFLD. Our data suggest that pancreatic fat should not be considered an inert accumulation of fat, but as an additional factor able to affect glucose metabolism and severity of liver disease, increasing the risk of develop metabolic syndrome.

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.

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Nonalcoholic steatohepatitis (NASH), a progressive form of nonalcoholic fatty liver disease, is one of the most common hepatic diseases in children. We conducted a randomized controlled clinical trial on children with biopsy-proven NASH based on a combinatorial nutritional approach compared with placebo. Participants were assigned to lifestyle modification plus placebo or lifestyle modification plus a mix containing docosahexaenoic acid, choline, and vitamin E (DHA-CHO-VE). Forty children and adolescents participated in the entire trial. The primary outcome was the improvement of liver hyperechogenicity. Secondary outcomes included alterations of alanine aminotransferase (ALT) and other metabolic parameters. Furthermore, changes of serum bile acids (BA) and plasma fibroblast growth factor 19 (FGF19) levels were evaluated as inverse biomarkers of disease severity. At the end of the study, we observed a significant decrease in severe steatosis in the treatment group (50% to 5%, p = 0.001). Furthermore, although the anthropometric and biochemical measurements in the placebo and DHA-CHO-VE groups were comparable at baseline, at the end of the study ALT and fasting glucose levels improved only in the treatment group. Finally, we found that BA levels were not influenced whereas FGF19 levels were significantly increased by DHA-CHO-VE. The results suggest that a combination of DHA, VE, and CHO could improve steatosis and reduce ALT and glucose levels in children with NASH. However, further studies are needed to assess the impact of a DHA and VE combination on repair of liver damage in paediatric NASH.

In children with NAFLD, there is an inverse relation between serum bilirubin levels and the presence of NASH on biopsy. This may be secondary to the antioxidant effect of bilirubin.

development of complications was reported. CONCLUSION:The therapeutic strategies were extremely heterogeneous. Ursodeoxycholic acid was ineffective in dissolution of gallstones but it had a positive effect on the symptoms. Laparoscopic cholecystectomy was confirmed to be an efficacy and safe treatment for pediatric gallstones. INTRODUCTIONIn the last years following the extensive use of ultrasound scanning an increasing number of children with cholelithiasis has been identified. In a population based study, prevalence of gallstones and biliary sludge in children was of 1.9% and 1.46%, respectively [1] . In an analogue study, performed in Italian adults, the overall prevalence of gallstones diseases was of 9.5% in men and 18.9% in women [2] . Gallstones disease is the most common and costly of all digestive disease in the United States, resulting in 700 000 cholecystectomies and as many as 1 000 000 hospitalizations annually [3] . The frequency of hospital admission and operation for gallstones increased in Western countries since the 1950s [4] . In England the age-standardized hospital admission rate for cholelithiasis enhanced from 68.7 to 104.9 per 100 000 population between 1989/1990 and 1999/2000 and it increased progressively with age from 1.1 per 100 000 in the 0-14 year age group to 277.1 per 100 000 in the ≥ 85-year age group in 1999/2000 [5] . Guidelines for management of cholelithiasis are available for adults. Cholecystectomy is recommended for

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