Nonalcoholic fatty liver disease (NAFLD) refers to a group of conditions characterized by hepatic steatosis in the absence of significant alcohol consumption. NAFLD is seen commonly in patients with metabolic abnormalities associated with obesity, such as type II diabetes, dyslipidemia, and metabolic syndrome. Evidently, however, not all obese subjects develop NAFLD and, more importantly, NAFLD can be found in nonobese individuals. Although NAFLD occurring in nonobese subjects has been reported in children and adults of all ethnicities, it appears to be recognized more frequently in Asians, even when strict ethnicityspecific body mass index criteria are used to define obesity. Studies based on liver biopsies suggest that the prevalence of nonalcoholic steatohepatitis and fibrosis does not differ significantly between nonobese NAFLD and NAFLD in obese patients. Visceral obesity as opposed to general obesity, high fructose and cholesterol intake, and genetic risk factors (eg, palatin-like phospholipase domain-containing 3) may be associated with nonobese NAFLD. In general, nonalcoholic steatohepatitis is associated with increased mortality, primarily from cardiovascular causes, independent of other metabolic factors. Although data regarding the mortality impact of nonobese NAFLD are not as mature, it may be important to identify high-risk nonobese NAFLD patients and manage their metabolic profile. Currently, lifestyle modification to reduce visceral adiposity, including dietary changes and physical activity, remains the standard of care in patients with nonobese NAFLD.
Intracellular components must be recycled for cells to maintain energy and ensure quality control of proteins and organelles. Autophagy is a highly conserved recycling process that involves degradation of cellular constituents in lysosomes. Although autophagy regulates a number of cell functions, it was first found to maintain energy balance in liver cells. As our understanding of autophagy has increased, we have found its connections to energy regulation in liver cells to be tight and complex. We review 3 mechanisms by which hepatic autophagy monitors and regulates cellular metabolism. Autophagy provides essential components (amino acids, lipids, and carbohydrates) required to meet the cell's energy needs, and it also regulates energy supply by controlling the number, quality, and dynamics of the mitochondria. Finally, autophagy also modulates levels of enzymes in metabolic pathways. In light of the multiple ways in which autophagy participates to control liver metabolism, it is no surprise that dysregulation of autophagy has been associated with metabolic diseases such as obesity, diabetes, or metabolic syndrome, as well as liver-specific disorders such as fatty liver, nonalcoholic steatohepatitis, and hepatocellular carcinoma. We discuss some of these connections and how hepatic autophagy might serve as a therapeutic target in common metabolic disorders.
The revised BSPGHAN guidelines for the diagnosis and management of coeliac disease represent an important shift in diagnostic strategy, aimed at simplifying and shortening the diagnostic process in selected cases. Guidance is given concerning the indications for testing for coeliac disease, which is still significantly underdiagnosed in the UK. While screening data suggest a likely incidence of 1 in 100 persons, only 10%-20% of this figure is currently being diagnosed. The BSPGHAN guidelines follow the new ESPGHAN guidelines in overall diagnostic strategy, while providing more didactic stratagems, which should be of assistance for paediatricians in specialties other than gastroenterology.
Attempts have been made to reveal the true nature of a range of puzzling diseases within gastroenterology and hepatology using different kinds of omics, namely genomics, transcriptomics, proteomics, and metabonomics [...