Non-Alcoholic Fatty Liver Disease (NAFLD) is now the most prevalent form of chronic liver disease, affecting 10%–20% of the general paediatric population. Within the next 10 years it is expected to become the leading cause of liver pathology, liver failure and indication for liver transplantation in childhood and adolescence in the Western world. While our understanding of the pathophysiological mechanisms underlying this disease remains limited, it is thought to be the hepatic manifestation of more widespread metabolic dysfunction and is strongly associated with a number of metabolic risk factors, including insulin resistance, dyslipidaemia, cardiovascular disease and, most significantly, obesity. Despite this, ”paediatric” NAFLD remains under-studied, under-recognised and, potentially, undermanaged. This article will explore and evaluate our current understanding of NAFLD in childhood and adolescence and how it differs from adult NAFLD, in terms of its epidemiology, pathophysiology, natural history, diagnosis and clinical management. Given the current absence of definitive radiological and histopathological diagnostic tests, maintenance of a high clinical suspicion by all members of the multidisciplinary team in primary and specialist care settings remains the most potent of diagnostic tools, enabling early diagnosis and appropriate therapeutic intervention.

Background. The incidence of nonalcoholic fatty liver disease (NAFLD) continues to parallel the rise in obesity rates. Endobariatric devices such as the intragastric balloon (IGB) may provide an alternative treatment option.Methods. Outcomes following IGB treatment in 135 patients with obesity and NAFLD (mean baseline weight 117.9 kg; BMI 41.7 kg/m²; HOMA-IR 3.6) were retrospectively examined. Clinical, anthropometric, and biochemical changes were analysed at six months and after consecutive treatment with two and three serial IGBs.Results. After six months, significant changes were seen with weight and BMI (mean reductions of 11.3 kg and 4.1 kg/m², resp.,p<0.01for both). Significant improvements were also seen with ALT, GGT, and HOMA-IR, with all changes corresponding with weight loss. Forty-eight patients received two IGBs, and 20 were treated with three serial IGBs. The greatest amount of total weight loss was observed after the first 6 months (mean weight lost 7.4 kg, versus 3.6 kg and 1.9 kg with two and three IGBs, resp.).Conclusions. IGB therapy is an effective, alternative nonsurgical means for weight loss in the management of obesity and NAFLD over the short term, with greatest outcomes observed after six months. Improvements in insulin resistance and hepatic transaminases correlated with weight change.

Maternal obesity predisposes offspring to metabolic dysfunction and Non-Alcoholic Fatty Liver Disease (NAFLD). Melanocortin-4 receptor (Mc4r)-deficient mouse models exhibit obesity during adulthood. Here, we aim to determine the influence of the Mc4r gene on the liver of mice subjected to perinatal diet-induced obesity. Female mice heterozygous for Mc4r fed an obesogenic or a control diet for 5 weeks were mated with heterozygous males, with the same diet continued throughout pregnancy and lactation, generating four offspring groups: control wild type (C_wt), control knockout (C_KO), obese wild type (Ob_wt), and obese knockout (Ob_KO). At 21 days, offspring were genotyped, weaned onto a control diet, and sacrificed at 6 months old. Offspring phenotypic characteristics, plasma biochemical profile, liver histology, and hepatic gene expression were analyzed. Mc4r_ko offspring showed higher body, liver and adipose tissue weights respect to the wild type animals. Histological examination showed mild hepatic steatosis in offspring group C_KO. The expression of hepatic genes involved in regulating inflammation, fibrosis, and immune cell infiltration were upregulated by the absence of the Mc4r gene. These results demonstrate that maternal obesogenic feeding during the perinatal period programs offspring obesity development with involvement of the Mc4r system.

Introduction: Subcutaneous (SC) administration of the anti-CD38 antibody isatuximab (Isa) by an on-body delivery system (OBDS), plus pomalidomide-dexamethasone, has demonstrated safety and efficacy comparable to intravenous (IV) administration, with no infusion reactions and excellent local tolerability in multiple myeloma (MM) patients. We report here results of a nurse survey designed to evaluate convenience of treatment with SC Isa, via OBDS, for healthcare providers and MM patients.Methods: A newly developed, expert-vetted questionnaire was used to survey nurses with experience in SC administration to MM patients enrolled in clinical trials. Results on extent of agreement with pre-vetted statements were expressed as percentages of respondents. Free-text answers were analyzed for each respondent and grouped by topic.Results: All surveyed nurses (N=12) agreed that OBDS administration improved efficiency and was easy to learn and administer with a low level of physical burden, leading to a preference for OBDS over IV Isa administration and facilitating a positive treatment experience for the patients. Compared with IV dosing, the OBDS improved patient comfort and could reduce time spent in the clinic. As agreed by most nurses, main advantages for patients included no needle visibility, short treatment duration, and a generally well-tolerated and painless SC injection.Conclusions: Our findings show a high level of confidence among nurses in SC Isa administration via OBDS, due to the ease of use, tolerability, and time savings achieved with hands-free OBDS injections. Our findings suggest applicability of the OBDS for convenient SC Isa administration to MM patients in routine clinical practice.