The management of tyrosinaemia type 1 (HT1, fumarylacetoacetase deficiency) has been revolutionised by the introduction of nitisinone but dietary treatment remains essential and the management is not easy. In this review detailed recommendations for the management are made based on expert opinion, published case reports and investigational studies as the evidence base is limited and there are no prospective controlled studies.The added value of this paper is that it summarises in detail current clinical knowledge about HT1 and makes recommendations for the management.

Background & Aims The diagnostic accuracy of hepatic ultrasonography for detection and grading of hepatic steatosis in children with suspected nonalcoholic fatty liver disease (NAFLD) remains poorly characterized. The aim of this study was to prospectively evaluate the clinical utility of ultrasonographic quantification of hepatic steatosis. Methods Our cohort consisted of 208 consecutive pediatric patients with biopsy-proven NAFLD. Hepatic ultrasonography was performed within 1-month of the liver biopsy procedure. Steatosis identified by ultrasonography was scored using a 0 to 3 scale based on echogenicity and visualization of vasculature, parenchyma and diaphragm and compared to histological features based on Brunt’s classification. Results The median age at time of first visit was 10.8 years and 64% were boys. Sixty-nine percent had moderate to severe steatosis on histology. Ultrasonographic steatosis score (USS) had an excellent correlation with histological grade of steatosis (with a Spearman’s coefficient of 0.80). The area under the receiver operating characteristic (ROC) curve for ultrasonographic detection of moderate to severe steatosis was 0.87. The USS did not correlate significantly with inflammatory activity or fibrosis stage; however, there was significant correlation with the NAFLD activity score (NAS) albeit this was due in large part to the strong correlation with the steatosis component of NAS. Serum ALT and AST were not associated with histological grade of steatosis and showed no correlation with USS. Conclusions Our results, which represent the largest prospective pediatric study evaluating the role of hepatic ultrasonography in children with biopsy-proven NAFLD, demonstrate the utility of this technique for non-invasive diagnosis and estimation of hepatic steatosis in children.

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.