Pediatric non-alcoholic fatty liver disease: an increasing public health issue

Non-alcoholic fatty liver disease (NAFLD) is now a major public health concern with an estimated prevalence of 25–30% of adults in many countries. Strongly associated with obesity and the metabolic syndrome, the pathogenesis of NAFLD is dependent on complex interactions between genetic and environmental factors that are not completely understood. Weight loss through diet and lifestyle modification underpins clinical management; however, the roles of individual dietary nutrients (e.g. saturated and n-3 fatty acids; fructose, vitamin D, vitamin E) in the pathogenesis or treatment of NAFLD are only partially understood. Systems biology offers valuable interdisciplinary methods that are arguably ideal for application to the studying of chronic diseases such as NAFLD, and the roles of nutrition and diet in their molecular pathogenesis. Although present in silico models are incomplete, computational tools are rapidly evolving and human metabolism can now be simulated at the genome scale. This paper will review NAFLD and its pathogenesis, including the roles of genetics and nutrition in the development and progression of disease. In addition, the paper introduces the concept of systems biology and reviews recent work utilising genome-scale metabolic networks and developing multi-scale models of liver metabolism relevant to NAFLD. A future is envisioned where individual genetic, proteomic and metabolomic information can be integrated computationally with clinical data, yielding mechanistic insight into the pathogenesis of chronic diseases such as NAFLD, and informing personalised nutrition and stratified medicine approaches for improving prognosis.

Download Full-text

Metabolic disturbances in non-alcoholic fatty liver disease

Clinical Science ◽

10.1042/cs20080253 ◽

2009 ◽

Vol 116 (7) ◽

pp. 539-564 ◽

Cited By ~ 154

Author(s):

Christopher D. Byrne ◽

Rasaq Olufadi ◽

Kimberley D. Bruce ◽

Felino R. Cagampang ◽

Mohamed H. Ahmed

Keyword(s):

Public Health ◽

Liver Disease ◽

Fatty Liver ◽

Health Problem ◽

Fatty Liver Disease ◽

Public Health Problem ◽

Alcoholic Fatty Liver ◽

Increased Risk ◽

Alcoholic Fatty Liver Disease ◽

Over Time

NAFLD (non-alcoholic fatty liver disease) refers to a wide spectrum of liver damage, ranging from simple steatosis to NASH (non-alcoholic steatohepatitis), advanced fibrosis and cirrhosis. NAFLD is strongly associated with insulin resistance and is defined by accumulation of liver fat >5% per liver weight in the presence of <10 g of daily alcohol consumption. The exact prevalence of NAFLD is uncertain because of the absence of simple non-invasive diagnostic tests to facilitate an estimate of prevalence. In certain subgroups of patients, such as those with Type 2 diabetes, the prevalence of NAFLD, defined by ultrasound, may be as high as 70%. NASH is an important subgroup within the spectrum of NAFLD that progresses over time with worsening fibrosis and cirrhosis, and is associated with increased risk for cardiovascular disease. It is, therefore, important to understand the pathogenesis of NASH and, in particular, to develop strategies for interventions to treat this condition. Currently, the ‘gold standard’ for the diagnosis of NASH is liver biopsy, and the need to undertake a biopsy has impeded research in subjects in this field. Limited results suggest that the prevalence of NASH could be as high as 11% in the general population, suggesting there is a worsening future public health problem in this field of medicine. With a burgeoning epidemic of diabetes in an aging population, it is likely that the prevalence of NASH will continue to increase over time as both factors are important risk factors for liver fibrosis. The purpose of this review is to: (i) briefly discuss the epidemiology of NAFLD to describe the magnitude of the future potential public health problem; and (ii) to discuss extra- and intra-hepatic mechanisms contributing to the pathogenesis of NAFLD, a better understanding of which may help in the development of novel treatments for this condition.

Download Full-text

Assessment of non-alcoholic fatty liver disease (NAFLD) severity with novel serum-based markers: A pilot study

PLoS ONE ◽

10.1371/journal.pone.0260313 ◽

2021 ◽

Vol 16 (11) ◽

pp. e0260313

Author(s):

Atul Goyale ◽

Anjly Jain ◽

Colette Smith ◽

Margarita Papatheodoridi ◽

Marta Guerrero Misas ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Positive Likelihood Ratio ◽

Public Health Issue ◽

Enzyme Linked Immunosorbent Assay ◽

Roc Curve Analysis ◽

Cross Sectional ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

Background/Aims Non-alcoholic fatty liver disease (NAFLD) represents a significant public health issue. Identifying patients with simple steatosis from those with non-alcoholic steatohepatitis (NASH) is crucial since NASH is correlated with increased morbidity and mortality. Serum-based markers, including adipokines and cytokines, are important in the pathogenesis and progression of NAFLD. Here we assessed the usefulness of such markers in patients with NAFLD. Methods This prospective, cross-sectional study included 105 adult patients with varying severity of NAFLD. Twelve serum-based markers were measured by 3 biochip platforms and 2 enzyme-linked immunosorbent assay (ELISA) methods. We also developed a NAFLD individual fibrosis index (NIFI) using the serum-based markers mostly correlated with fibrosis severity. Results Sixty-one out of 105 patients were male (58.1%) with mean age was 53.5 years. Higher Interleukin-6 (IL-6) increased (p = 0.0321) and lower Matrix Metalloproteinase-9 (MMP-9) serum levels (p = 0.0031) were associated with higher fibrosis as measured by Fibroscan® in multivariable regression analysis. Using receiver-operating characteristic (ROC) curve analysis for the NIFI, area under the curve for predicting Fibroscan values ≥ 7.2 kPa was 0.77 (95%CI: 0.67, 0.88, p<0.001), with sensitivity of 89.3%, specificity of 57.9% and a positive likelihood ratio of 2.8. Conclusions Increasing fibrosis severity in NAFLD is associated with differential expression of IL-6 and MMP-9. NIFI could be valuable for the prediction of advanced NAFLD fibrosis and potentially help avoid unnecessary interventions such as liver biopsy in low-risk patients.

Download Full-text