Hannah I. Awai

Paediatric gastroenterology evaluation of overweight and obese children referred from primary care for suspected non-alcoholic fatty liver disease

Screening overweight and obese children for non‐alcoholic fatty liver disease (NAFLD) is recommended by paediatric and endocrinology societies. However, gastroenterology societies have called for more data before making a formal recommendation.

Magnetic resonance imaging and liver histology as biomarkers of hepatic steatosis in children with nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children. In order to advance the field of NAFLD, noninvasive imaging methods for measuring liver fat are needed. Advanced magnetic resonance imaging (MRI) has shown great promise for the quantitative assessment of hepatic steatosis but has not been validated in children. Therefore, this study was designed to evaluate the correlation and diagnostic accuracy of MRI‐estimated liver proton density fat fraction (PDFF), a biomarker for hepatic steatosis, compared to histologic steatosis grade in children. The study included 174 children with a mean age of 14.0 years. Liver PDFF estimated by MRI was significantly (P < 0.01) correlated (0.725) with steatosis grade. The correlation of MRI‐estimated liver PDFF and steatosis grade was influenced by both sex and fibrosis stage. The correlation was significantly (P < 0.01) stronger in girls (0.86) than in boys (0.70). The correlation was significantly (P < 0.01) weaker in children with stage 2‐4 fibrosis (0.61) than children with no fibrosis (0.76) or stage 1 fibrosis (0.78). The diagnostic accuracy of commonly used threshold values to distinguish between no steatosis and mild steatosis ranged from 0.69 to 0.82. The overall accuracy of predicting the histologic steatosis grade from MRI‐estimated liver PDFF was 56%. No single threshold had sufficient sensitivity and specificity to be considered diagnostic for an individual child. Conclusions: Advanced magnitude‐based MRI can be used to estimate liver PDFF in children, and those PDFF values correlate well with steatosis grade by liver histology. Thus, magnitude‐based MRI has the potential for clinical utility in the evaluation of NAFLD, but at this time no single threshold value has sufficient accuracy to be considered diagnostic for an individual child. (Hepatology 2015;61:1887–1895)

Liver toxicity of anabolic androgenic steroid use in an adolescent with nonalcoholic fatty liver disease.

The prevalence of obesity and related morbidities such as nonalcoholic fatty liver disease (NAFLD) is high among adolescents. Current treatment recommendations for NAFLD focus on lifestyle optimization via nutrition and exercise. After encouraging exercise, many adolescents choose to participate in organized sports, which may lead to use of illicit substances such as anabolic androgenic steroids (AAS) to boost athletic performance. Approximately 3,000,000 individuals use non-therapeutic AAS at supra-physiologic doses in the United States.1 In 2012, 5.9% of adolescent boys reported steroid use in the previous year.2 We anticipate adolescents with pre-existing liver disease are at increased risk for AAS induced hepatotoxicity. We present such a case with IRB approval and written individual patient consent.

Liver histology and diffusion‐weighted MRI in children with nonalcoholic fatty liver disease: A MAGNET study

To determine potential associations between histologic features of pediatric nonalcoholic fatty liver disease (NAFLD) and estimated quantitative magnetic resonance diffusion‐weighted imaging (DWI) parameters.

Holding the Record for Retention of an Endoscopy Capsule.

W ireless capsule endoscopy (WCE) is an important tool for direct visualization of the small bowel without associated risks of radiation or sedation in youth who are able to swallow the capsule. The Food and Drug Administration has approved WCE usage in children for evaluation of gastrointestinal bleeding and small bowel disease. Although noninvasive, WCE carries certain risks, particularly capsule retention. To our knowledge, we describe the longest reported case of capsule retention. A 10-year-old well-appearing boy with a history of surgically repaired congenital duodenal atresia and pyloric stenosis as well as intestinal adhesions requiring lysis presented to his primary care pediatrician for evaluation of acute abdominal pain, which subsequently resolved during a 2-day period. His pediatrician performed an abdominal x-ray and found a foreign body consistent with a WCE at the right abdomen (Fig. 1). Further interview revealed that the patient was admitted at 2 years old for 2 months at an out-of-state institution for the evaluation of gastrointestinal bleeding. WCE evaluation during that admission revealed multiple small arteriovenous malformations isolated to the small bowel; these were managed with supportive care and blood transfusion. During the patient’s hospital stay, the patient’s family reported multiple changes in physicians, and ultimately the patient was discharged without WCE passage. Patient was initially studied with serial abdominal x-rays until he was lost to follow-up 7 months after the WCE placement. The patient was referred to our pediatric gastroenterology clinic for intestinal foreign body evaluation. At the clinic visit, the patient was asymptomatic. Physical examination was unremarkable outside of positive stool guaiac testing. Body mass index was 87% (19.7 kg/m). Hemoglobin was 13.3 g/dL with normal red blood cell indices. A computed tomography revealed a radiodense body consistent with the WCE in the proximal small bowel and distention of small bowel loops consistent with partial obstruction from adhesions (Fig. 2). The patient underwent surgical consultation to undergo surgical removal of the retained WCE. To date, the family has, however, decided against surgical intervention because of lack of patient symptoms and ongoing fear of surgical complications. An alternative to surgical removal of WCE is endoscopic removal. The case was, however, reviewed with both local and national experts and it was felt that removal should be deferred given that the benefits may not outweigh the risks of intervention. We have adopted a management plan of watchful waiting and have

Letter: gender-associated cell-free microRNA profiles in non-alcoholic fatty liver disease--authors' reply.

SIRS, Longchamps et al. used the differences between boys and girls in paediatric non-alcoholic fatty liver disease (NAFLD) reported in our study as an entry point to discuss the development of gender-specific biomarkers further. In our cohort of obese children screened for liver disease in primary care, boys had higher ALT than girls. This gender difference in ALT is consistent with previous studies. For example, in the SAFETY study, the 95th percentile levels for ALT in healthy weight, metabolically normal children without liver disease were 25.8 U/L (boys) and 22.1 U/L (girls). Although gender differences exist, ALT has been shown to be a useful screening test for liver disease in obese children, but results must be interpreted correctly. ALT elevation indicates a possible problem in the liver; however, it does not determine either the aetiology or severity of the problem. As demonstrated in our study, liver histology remains an invaluable tool both for making the correct diagnosis and for grading and staging the disease severity. The development of biomarkers is of great interest to evaluate children with NAFLD. Of the current biomarkers under consideration, none has been suggested to be used as a screening tool. A successful biomarker for NAFLD would play a role in the diagnostic confirmation of NAFLD, as well as in determining disease severity. Most studies of potential biomarkers for NAFLD in children, however, have been small and cross-sectional. Large external validations are still needed. The potential of microRNAs (miRNAs) as biomarkers of disease severity in the context of NAFLD has been recently explored. miRNAs are small noncoding RNAs with key roles in gene regulation. Several miRNAs are specifically enriched in the liver and may be released into the circulation during liver damage, and thus have sparked an interest as potential mechanism-based, tissue-specific biomarkers. Early proofof-concept studies demonstrated that plasma levels of miR-122 and miR-192, two liver-enriched microRNAs could be detected early after acetaminophen exposure in mice. In the current letter, Longchamps et al. add to the literature by suggesting a gender difference in blood levels of various miRNAs being higher in male vs. female patients with NAFLD. These data, however, were based upon a total of five patients with NAFLD. Although intriguing, these differences require exploration in larger, appropriately powered studies. Key areas for future investigation of microRNAs as potential biomarkers in NAFLD include assessing the mechanisms and kinetics of liver microRNA release into blood, and establishing the different compartments, such as extracellular vesicles, that comprise the predominant source of circulating miRNAs in NAFLD.

Nonalcoholic Fatty Liver Disease in Children

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the pediatric population, present in 3–12 % of children from industrialized nations. In children, NAFLD is more common in boys than girls. The prevalence of NAFLD increases with age and with obesity. The pathogenesis is influenced by maternal factors such as preconception weight and gestational diabetes. Guidelines exist that recommend screening obese children for NAFLD; however, there is controversy in the implementation of these guidelines. In children, the available evidence does not support the use of ultrasound for diagnosis or grading of fatty liver. MRI is promising, but at this time does not have sufficient accuracy to be considered diagnostic for an individual child. Diagnosis of NAFLD in children ultimately requires liver biopsy. The histology of NAFLD in children differs from that of adults and is characterized by more severe steatosis, greater portal inflammation and fibrosis, and less hepatocyte ballooning and perisinusoidal fibrosis. Advanced fibrosis has been reported in 5–15 % of children with NAFLD. Cardiovascular outcomes are also important as children with NAFLD have high rates of dyslipidemia, hypertension, and left ventricular structural and functional abnormalities. Adolescence is a vulnerable developmental period, and anxiety, depression, and impaired quality of life are all common in pediatric NAFLD. Clinical management is focused on the assessment of and improvement in global health with an emphasis on lifestyle optimization. Because of the prevalence and severity of NAFLD in children, targeted therapies are a pressing need.