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Open AccessArticle

Natural History of NAFLD Diagnosed in Childhood: A Single-Center Study

by Catherine E. Cioffi, Jean A. Welsh, Rebecca L. Cleeton, Shelley A. Caltharp, Rene Romero, Mark L. Wulkan, Juna V. Konomi, Jennifer K. Frediani and Miriam B. Vos

Children 2017, 4(5), 34; https://doi.org/10.3390/children4050034 - 03 May 2017

Cited by 23 | Viewed by 6659

Abstract

Little is known regarding the subsequent course of non-alcoholic fatty liver disease (NAFLD) diagnosed in childhood. The objectives of this single-center study were to gather data on long-term health outcomes and to assess the feasibility of contacting former pediatric patients. In a large [...] Read more.

Little is known regarding the subsequent course of non-alcoholic fatty liver disease (NAFLD) diagnosed in childhood. The objectives of this single-center study were to gather data on long-term health outcomes and to assess the feasibility of contacting former pediatric patients. In a large pediatric medical center, electronic records were searched to initially identify 162 former patients who had a liver biopsy between 2000 and 2010. Of these, 44 subjects met the criteria for age at follow-up (≥18 year) and biopsy-proven NAFLD, and were recruited via postal and electronic mail. Participants were invited to complete a brief telephone survey on current health status. Supplemental data was also obtained from pediatric medical charts of all subjects. At NAFLD diagnosis, 18% of subjects had diabetes, 91% were obese, 61% had NASH, and 56% had fibrosis on biopsy. At follow-up, 10 subjects (23%) responded to the survey. Based on the survey and chart review, after a mean follow-up of 4.5 years, 5 additional subjects developed diabetes for a period prevalence of 30%, and most subjects (78%) remained obese at last follow-up. Additional prospective studies are needed to fully describe the longitudinal risks associated with pediatric NAFLD, and will require multi-dimensional strategies to successfully recruit former patients. Full article

(This article belongs to the Special Issue Pediatric Nonalcoholic Fatty Liver Disease)

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Review

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Open AccessReview

Insulin Resistance and NAFLD: A Dangerous Liaison beyond the Genetics

by Melania Manco

Children 2017, 4(8), 74; https://doi.org/10.3390/children4080074 - 14 Aug 2017

Cited by 45 | Viewed by 6324

Abstract

Over the last decade, the understanding of the association between insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) has dramatically evolved. There is clear understanding that carriers of some common genetic variants, i.e., the patatin-like phospholipase domain-containing 3 (PNPLA3) or the transmembrane [...] Read more.

Over the last decade, the understanding of the association between insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) has dramatically evolved. There is clear understanding that carriers of some common genetic variants, i.e., the patatin-like phospholipase domain-containing 3 (PNPLA3) or the transmembrane 6 superfamily member 2 (TM6SF2) are at risk of developing severe forms of NAFLD even in the presence of reduced or absent IR. In contrast, there are obese patients with “metabolic” (non-genetically driven) NAFLD who present severe IR. Owing to the epidemic obesity and the high prevalence of these genetic variants in the general population, the number of pediatric cases with combination of genetic and metabolic NAFLD is expected to be very high. Gut dysbiosis, excessive dietary intake of saturated fats/fructose-enriched foods and exposure to some chemicals contribute all to both IR and NAFLD, adding further complexity to the understanding of their relationship. Once NAFLD is established, IR can accelerate the progression to the more severe form of liver derangement that is the non-alcoholic steatohepatitis. Full article

(This article belongs to the Special Issue Pediatric Nonalcoholic Fatty Liver Disease)

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Open AccessReview

Imaging Features of Non-Alcoholic Fatty Liver Disease in Children and Adolescents

by Michele Di Martino, Kameliya Koryukova, Mario Bezzi and Carlo Catalano

Children 2017, 4(8), 73; https://doi.org/10.3390/children4080073 - 11 Aug 2017

Cited by 15 | Viewed by 18346

Abstract

Non-invasive diagnosis and quantification of liver steatosis is important to overcome limits of liver biopsy, in order to follow up patients during their therapy and to establish a reference standard that can be used in clinical trials and longitudinal studies. Imaging offers several [...] Read more.

Non-invasive diagnosis and quantification of liver steatosis is important to overcome limits of liver biopsy, in order to follow up patients during their therapy and to establish a reference standard that can be used in clinical trials and longitudinal studies. Imaging offers several methods in this setting: ultrasound, which is the cheapest technique and easy to perform; magnetic resonance spectroscopy (MRS), which reflects the real content of triglycerides in a specific volume; and proton density fat fraction (PDFF) magnetic resonance, which is a simple method that reflects the distribution of the fat in the whole liver. Other techniques include ultrasound elastography (EUS) and magnetic resonance elastrography (MRE), which can evaluate the progression of non-alcoholic fatty liver disease (NAFLD) into non-alcoholic steato-hepatitis (NASH) and cirrhosis, by quantifying liver fibrosis. Full article

(This article belongs to the Special Issue Pediatric Nonalcoholic Fatty Liver Disease)

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Gut–Liver Axis Derangement in Non-Alcoholic Fatty Liver Disease

by Marco Poeta, Luca Pierri and Pietro Vajro

Children 2017, 4(8), 66; https://doi.org/10.3390/children4080066 - 02 Aug 2017

Cited by 94 | Viewed by 11851

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most frequent type of chronic liver disease in the pediatric age group, paralleling an obesity pandemic. A “multiple-hit” hypothesis has been invoked to explain its pathogenesis. The “first hit” is liver lipid accumulation in obese children [...] Read more.

Non-alcoholic fatty liver disease (NAFLD) is the most frequent type of chronic liver disease in the pediatric age group, paralleling an obesity pandemic. A “multiple-hit” hypothesis has been invoked to explain its pathogenesis. The “first hit” is liver lipid accumulation in obese children with insulin resistance. In the absence of significant lifestyle modifications leading to weight loss and increased physical activity, other factors may act as “second hits” implicated in liver damage progression leading to more severe forms of inflammation and hepatic fibrosis. In this regard, the gut–liver axis (GLA) seems to play a central role. Principal players are the gut microbiota, its bacterial products, and the intestinal barrier. A derangement of GLA (namely, dysbiosis and altered intestinal permeability) may promote bacteria/bacterial product translocation into portal circulation, activation of inflammation via toll-like receptors signaling in hepatocytes, and progression from simple steatosis to non-alcoholic steato-hepatitis (NASH). Among other factors a relevant role has been attributed to the farnesoid X receptor, a nuclear transcriptional factor activated from bile acids chemically modified by gut microbiota (GM) enzymes. The individuation and elucidation of GLA derangement in NAFLD pathomechanisms is of interest at all ages and especially in pediatrics to identify new therapeutic approaches in patients recalcitrant to lifestyle changes. Specific targeting of gut microbiota via pre-/probiotic supplementation, feces transplantation, and farnesoid X receptor modulation appear promising. Full article

(This article belongs to the Special Issue Pediatric Nonalcoholic Fatty Liver Disease)

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The Association between Non-Alcoholic Fatty Liver Disease and Cardiovascular Risk in Children

by Anna Di Sessa, Giuseppina Rosaria Umano and Emanuele Miraglia del Giudice

Children 2017, 4(7), 57; https://doi.org/10.3390/children4070057 - 07 Jul 2017

Cited by 13 | Viewed by 4648

Abstract

The rising prevalence of childhood obesity in the past decades has made Non-Alcoholic Fatty Liver Disease (NAFLD) the most common cause of pediatric chronic liver disease worldwide. Currently, a growing body of evidence links NAFLD with cardiovascular disease (CVD) even at an early [...] Read more.

The rising prevalence of childhood obesity in the past decades has made Non-Alcoholic Fatty Liver Disease (NAFLD) the most common cause of pediatric chronic liver disease worldwide. Currently, a growing body of evidence links NAFLD with cardiovascular disease (CVD) even at an early age. Data on the pediatric population have shown that NAFLD could represent an independent risk factor not only for cardiovascular events but also for early subclinical abnormalities in myocardial structure and function. Briefly, we review the current knowledge regarding the relationship between pediatric NAFLD and cardiovascular risk in an attempt to clarify our understanding of NAFLD as a possible cardiovascular risk factor in childhood. Full article

(This article belongs to the Special Issue Pediatric Nonalcoholic Fatty Liver Disease)

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Open AccessReview

The Association between Pediatric NAFLD and Common Genetic Variants

by Giuseppina Rosaria Umano, Mariangela Martino and Nicola Santoro

Children 2017, 4(6), 49; https://doi.org/10.3390/children4060049 - 18 Jun 2017

Cited by 11 | Viewed by 4990

Abstract

Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of obesity. Several studies have shown that genetic predisposition probably plays an important role in its pathogenesis. In fact, in the last few years a large number of genetic studies have [...] Read more.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of obesity. Several studies have shown that genetic predisposition probably plays an important role in its pathogenesis. In fact, in the last few years a large number of genetic studies have provided compelling evidence that some gene variants, especially those in genes encoding proteins regulating lipid metabolism, are associated with intra-hepatic fat accumulation. Here we provide a comprehensive review of the gene variants that have affected the natural history of the disease. Full article

(This article belongs to the Special Issue Pediatric Nonalcoholic Fatty Liver Disease)

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Open AccessReview

Pediatric Non-Alcoholic Fatty Liver Disease

by Haley Bush, Pegah Golabi and Zobair M. Younossi

Children 2017, 4(6), 48; https://doi.org/10.3390/children4060048 - 09 Jun 2017

Cited by 39 | Viewed by 7217

Abstract

Abstract: With the increase in the prevalence of obesity, non-alcoholic fatty liver disease (NAFLD) has become among the leading causes of chronic liver disease in the pediatric age group. Once believed to be a “two-hit process”, it is now clear that the [...] Read more.

Abstract: With the increase in the prevalence of obesity, non-alcoholic fatty liver disease (NAFLD) has become among the leading causes of chronic liver disease in the pediatric age group. Once believed to be a “two-hit process”, it is now clear that the actual pathophysiology of NAFLD is complex and involves multiple pathways. Moreover, NAFLD is not always benign, and patients with non-alcoholic steatohepatitis (NASH) are at increased risk of developing advanced stages of liver disease. It has also been shown that NAFLD is not only a liver disease, but is also associated with multiple extrahepatic manifestations, including cardiovascular diseases, type 2 diabetes, and low bone mineral density. Although the data is scarce in the pediatric population, some studies have suggested that long-term mortality and the requirement of liver transplantation will continue to increase in patients with NAFLD. More studies are needed to better understand the natural history of NAFLD, especially in the pediatric age group. Full article

(This article belongs to the Special Issue Pediatric Nonalcoholic Fatty Liver Disease)

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Open AccessReview

The Role of Lipid and Lipoprotein Metabolism in Non‐Alcoholic Fatty Liver Disease

by Francesco Massimo Perla, Maurizia Prelati, Michela Lavorato, Daniele Visicchio and Caterina Anania

Children 2017, 4(6), 46; https://doi.org/10.3390/children4060046 - 06 Jun 2017

Cited by 97 | Viewed by 11794

Abstract

Due to the epidemic of obesity across the world, nonalcoholic fatty liver disease (NAFLD) has become one of the most prevalent chronic liver disorders in children and adolescents. NAFLD comprises a spectrum of fat-associated liver conditions that can result in end-stage liver disease [...] Read more.

Due to the epidemic of obesity across the world, nonalcoholic fatty liver disease (NAFLD) has become one of the most prevalent chronic liver disorders in children and adolescents. NAFLD comprises a spectrum of fat-associated liver conditions that can result in end-stage liver disease and the need for liver transplantation. Simple steatosis, or fatty liver, occurs early in NAFLD and may progress to nonalcoholic steatohepatitis, fibrosis and cirrhosis with increased risk of hepatocellular carcinoma. The mechanism of the liver injury in NAFLD is currently thought to be a “multiple-hit process” where the first “hit” is an increase in liver fat, followed by multiple additional factors that trigger the inflammatory activity. At the onset of disease, NAFLD is characterized by hepatic triglyceride accumulation and insulin resistance. Liver fat accumulation is associated with increased lipotoxicity from high levels of free fatty acids, free cholesterol and other lipid metabolites. As a consequence, mitochondrial dysfunction with oxidative stress and production of reactive oxygen species and endoplasmic reticulum stress-associated mechanisms, are activated. The present review focuses on the relationship between intra-cellular lipid accumulation and insulin resistance, as well as on lipid and lipoprotein metabolism in NAFLD. Full article

(This article belongs to the Special Issue Pediatric Nonalcoholic Fatty Liver Disease)

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