Paediatric non‐alcoholic fatty liver disease: an overview

Non‐alcoholic fatty liver disease (NAFLD) is a progressive disease that encompasses a spectrum of liver diseases, ranging from simple steatosis to non‐alcoholic steatohepatitis (NASH). Data related to survival in children are scarce, but these data firmly associate NAFLD with higher risks of hepatic and non‐hepatic morbidities and mortalities compared with the general population. More recently, the association between NAFLD and cardiovascular disease among children has increasingly been recognized. Given that obesity is a major risk factor for the disease, paediatric NAFLD is becoming a global issue, paralleling the dramatic rise in obesity worldwide. NASH, which is more common in obese children, has the potential to advance to liver fibrosis and failure. It is unclear why certain patients undergo such transformation but this susceptibility is likely related to an interaction between a genetically susceptible host and the surrounding environment. Currently, treatment is largely conservative and includes lifestyle modification, attainable through healthy weight reduction via diet and exercise. In this review, current knowledge about NAFLD in children is summarized. This review aims to increase the awareness of the medical community about a hidden public health issue and to identify current gaps in the literature while providing directions for future research.     

Relationship of non‐alcoholic fatty liver disease to colorectal adenomatous polyps

Background and Aims: Metabolic syndrome and insulin resistance are associated with a higher risk of colon cancer. Non‐alcoholic fatty liver disease (NAFLD) is regarded as a manifestation of metabolic syndrome in the liver. This investigation was initiated to determine whether NAFLD has a relationship to colorectal adenomatous polyps. Methods: We examined the 2917 participants who underwent a routine colonoscopy at Kangbuk Samsung Hospital in 2007. We divided the 2917 subjects into the adenomatous polyp group (n = 556) and the normal group (n = 2361). Anthropometric measurements, biochemical tests for liver and metabolic function, and abdominal ultrasonographs were assessed. Results: The prevalence of NAFLD was 41.5% in the adenomatous polyp group and 30.2% in the control group. By multiple logistic regression analysis, NAFLD was found to be associated with an increased risk of colorectal adenomatous polyps (odds ratio, 1.28; 95% confidence interval, 1.03–1.60). An increased risk for NAFLD was more evident in patients with a greater number of adenomatous polyps. Conclusion: NAFLD was associated with colorectal adenomatous polyps. Further studies are needed to confirm whether NAFLD is a predictor for the development of colorectal adenomatous polyps and cancer.     

GLP‐1 receptor agonists: effects on the progression of non‐alcoholic fatty liver disease

Non‐alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases, and its incidence has been increasing recently. In addition to hepatic complications, NAFLD is also recognized as an independent risk factor for cardiovascular disease. Unfortunately, the current therapies for NAFLD display variable efficacy; a novel and effective drug is urgently needed. Glucagon‐like peptide‐1 (GLP‐1), a receptor agonist is a new drug approved for treating type 2 diabetes. Recently, these types of agents have shown a novel therapeutic effect on NAFLD. However, the mechanisms of GLP‐1 receptor agonists on the treatment of NAFLD have not yet been explained precisely. Recent studies have demonstrated that GLP‐1 reverses the progression of NAFLD not only indirectly through an incretin effect that improves key parameters involved in NAFLD, but also a direct effect on lipid metabolism of hepatocytes and inflammation in liver. In this review, we provided an overview of the role and mechanisms of GLP‐1 in the therapy of NAFLD. Copyright © 2014 John Wiley & Sons, Ltd.     

The role of adiponectin in the pathogenesis and treatment of non‐alcoholic fatty liver disease

Non‐alcoholic fatty liver disease (NAFLD) is recognized as the most common type of chronic liver disease in Western countries and the leading cause of cryptogenic cirrhosis. Insulin resistance (IR) is a key factor in the pathogenesis of NAFLD, the latter being considered as the hepatic component of IR or metabolic syndrome (MetS). Although the pathogenesis of NAFLD is not fully elucidated, a complex interaction between adipokines and cytokines produced by adipocytes and/or inflammatory cells infiltrating adipose tissue appears to play a crucial role in MetS and NAFLD. Adiponectin is the most abundant and adipose‐specific adipokine. In the liver, adiponectin acts through the activation of 5‐AMP‐activated protein kinase and peroxisome proliferator‐activated receptor‐α pathways and inhibition of toll‐like receptor‐4 mediated signalling. There is an evidence that adiponectin decreases hepatic and systematic IR and attenuates liver inflammation and fibrosis. Adiponectin generally predicts steatosis grade and severity of NAFLD, but it remains to be addressed to what extent this is a direct effect or related to the presence of more severe IR. Although there is no proven pharmacotherapy for the treatment of NAFLD, recent therapeutic strategies have focused on the indirect upregulation of adiponectin through the administration of various therapeutic agents and/or lifestyle modifications. Weight loss, through diet, lifestyle changes and/or medications including orlistat, sibutramine, rimonabant or bariatric surgery, increase adiponectin and may improve liver histology. Insulin sensitizers, including pioglitazone and rosiglitazone, and lipid‐lowering agents, including statins and fibrates, also upregulate adiponectin and ameliorate liver histology. The wider use of new treatment approaches appears to signal the dawn of a new era in the management of NAFLD. In this adiponectin‐focused review, the pathogenetic role and the potential therapeutic benefits of adiponectin in NAFLD are systematically analysed.     

Diagnosis and classification of non‐alcoholic fatty liver disease and non‐alcoholic steatohepatitis: Current concepts and remaining challenges

The high prevalence of non‐alcoholic fatty liver disease (NAFLD) has made the condition an important public health issue. Two clinical entities are manifestations of NAFLD, namely, non‐alcoholic fatty liver (NAFL) and non‐alcoholic steatohepatitis (NASH). The former tends to be benign and non‐progressive while the latter can progress to cirrhosis, which in rare cases gives rise to hepatocellular carcinoma. The diagnosis of NAFLD is based on: (i) a history of no or limited daily alcohol intake (<20 g for women and <30 g for men); (ii) presence of hepatic steatosis by imaging or by histology; and (iii) exclusion of other liver diseases. NAFL is defined histologically by the presence of bland, primarily macrovesicular, hepatocellular fatty change, while NASH features fatty change with inflammation and evidence of hepatocyte injury, such as ballooning degeneration. Presence of fibrosis is a sign of chronicity. Thus, the diagnosis of NAFL/NASH rests on clinicopathological criteria; it always requires both clinical and biopsy‐based information. NAFLD could be both the result and the cause of metabolic syndrome, with a vicious cycle operating between these conditions. Remaining challenges are: (i) the lack of a clear threshold alcohol intake for defining “non‐alcoholic”; (ii) a lacking consensus for the classification of fatty liver disease; and (iii) absence of a histological definition of NASH, which currently remains the gold standard for the diagnosis. Further challenges include the overlap of the criteria for NAFLD and alcoholic liver disease as many obese individuals also consume considerable volumes of alcohol.