8 research outputs found
Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease
OBJECTIVE:
To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines.
STUDY DESIGN:
This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention.
RESULTS:
There were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications.
CONCLUSIONS:
More than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management
In Children with Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis is Associated with Advanced Fibrosis
Background & Aims
Focal zone 1 steatosis, although rare in adults with nonalcoholic fatty liver disease (NAFLD), does occur in children with NAFLD. We investigated whether focal zone 1 steatosis and focal zone 3 steatosis are distinct subphenotypes of pediatric NAFLD. We aimed to determine associations between the zonality of steatosis and demographic, clinical, and histologic features in children with NAFLD.
Methods
We performed a cross-sectional study of baseline data from 813 children (age <18 years; mean age, 12.8 ± 2.7 years). The subjects had biopsy-proven NAFLD and were enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network. Liver histology was reviewed using the Nonalcoholic Steatohepatitis Clinical Research Network scoring system.
Results
Zone 1 steatosis was present in 18% of children with NAFLD (n = 146) and zone 3 steatosis was present in 32% (n = 244). Children with zone 1 steatosis were significantly younger (10 vs 14 years; P < .001) and a significantly higher proportion had any fibrosis (81% vs 51%; P < .001) or advanced fibrosis (13% vs 5%; P < .001) compared with children with zone 3 steatosis. In contrast, children with zone 3 steatosis were significantly more likely to have steatohepatitis (30% vs 6% in children with zone 1 steatosis; P < .001).
Conclusions
Children with zone 1 or zone 3 distribution of steatosis have an important subphenotype of pediatric NAFLD. Children with zone 1 steatosis are more likely to have advanced fibrosis and children with zone 3 steatosis are more likely to have steatohepatitis. To achieve a comprehensive understanding of pediatric NAFLD, studies of pathophysiology, natural history, and response to treatment should account for the zonality of steatosis
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Posttransplant metabolic syndrome in children and adolescents after liver transplantation: A systematic review
During long-term follow-up, 18% to 67% of pediatric liver transplant recipients are overweight or obese, with rates varying by age and pretransplant weight status. A similar prevalence of posttransplant obesity has been seen in adults. Adults also develop posttransplant metabolic syndrome and, consequently, cardiovascular disease at rates that exceed the rates in age- and sex-matched populations. Posttransplant metabolic syndrome has never been studied in pediatric liver transplant recipients, and this population is growing as transplant outcomes continue to improve. Here we systematically review the literature for each component of metabolic syndrome-obesity, hypertension, dyslipidemia, and glucose intolerance-in pediatric liver transplant recipients. Their rates of obesity are similar to the rates in children in the general U.S. population. However, hypertension, dyslipidemia, and diabetes are more common than would be expected in transplant recipients according to age, sex, and obesity severity. Immunosuppressive medications are major contributors. The limitations of previous studies, including heterogeneous methods of diagnosis, follow-up times, and immunosuppressive regimens, hinder the analysis of risk factors. Importantly, no studies have reported graft or patient outcomes associated with components of metabolic syndrome after pediatric liver transplantation. However, if the trends in children are similar to the trends seen in adults, these conditions may lead to significant long-term morbidity. Further research on the prevalence, causes, and consequences of posttransplant metabolic syndrome in pediatric liver transplant recipients is needed and will ultimately help to improve long-term outcomes
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Impact of the donor body mass index on the survival of pediatric liver transplant recipients and post-transplant obesity.
In adult liver transplant recipients, the donor body mass index (dBMI) is associated with posttransplant obesity but not with graft or patient survival. Because of the obesity epidemic in the United States and the already limited supply of liver donors, clarifying whether the dBMI affects pediatric outcomes is important. United Network for Organ Sharing data for pediatric liver transplants in the United States (1990-2010) were evaluated. Data on transplants performed between 2004 and 2010 (n = 3788) were used for survival analyses with Kaplan-Meier and Cox proportional hazards models and for posttransplant obesity analyses with generalized estimating equations. For children receiving adult donor livers, a dBMI of 25 to <35 kg/m(2) was not associated with graft or patient survival in univariate or multivariate analyses. A dBMI ≥ 35 kg/m(2) increased the risk of graft loss [hazard ratio (HR) = 2.54, 95% confidence interval (CI) = 1.29-5.01, P = 0.007] and death (HR = 3.56, 95% CI = 1.64-7.72, P = 0.001). For pediatric donors, the dBMI was not associated with graft loss or mortality in a univariate or multivariate analysis. An overweight or obese donor was not a risk factor for posttransplant obesity. Overweight and obesity are common among liver transplant donors. This analysis suggests that for adult donors, a body mass index (BMI) of 25 to <35 kg/m(2) should not by itself be a contraindication to liver donation. Severe obesity (BMI ≥ 35 kg/m(2)) in adult donors increased the risk of graft loss and mortality, even after adjustments for recipient, donor, and transplant risk factors. Posttransplant obesity was not associated with the dBMI in this analysis. Further research is needed to clarify the impact of donor obesity on pediatric liver transplant recipients
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Progression of Fatty Liver Disease in Children Receiving Standard of Care Lifestyle Advice
Background & aimsNonalcoholic fatty liver disease (NAFLD) is the most common pediatric chronic liver disease. Little is known about outcomes in recognized youth.MethodsWe compared paired liver biopsies from 122 of 139 children with NAFLD (74% male; 64% white; 71% Hispanic; mean age, 13 ± 3 years; age range, 8-17 years) who received placebo and standard of care lifestyle advice in 2 double-blind, randomized clinical trials within the nonalcoholic steatohepatitis (NASH) clinical research network from 2005 through 2015. We analyzed histologic changes with respect to baseline and longitudinal change in clinical variables using regression analysis.ResultsAt enrollment, 31% of the children had definite NASH, 34% had borderline zone 1 NASH, 13% had borderline zone 3 NASH, and 21% had fatty liver but not NASH. Over a mean period of 1.6 ± 0.4 years, borderline or definite NASH resolved in 29% of the children, whereas 18% of the children with fatty liver or borderline NASH developed definite NASH. Fibrosis improved in 34% of the children but worsened in 23%. Any progression to definite NASH and/or in fibrosis was associated with adolescent age, and higher waist circumference, levels of alanine or aspartate aminotransferase, total and low-density lipoprotein cholesterol at baseline (<0.05), and over follow-up time, with increasing level of alanine aminotransferase, hemoglobin A1C (P<.05), gamma-glutamyl transferase and development of type 2 diabetes (P<.01). Increasing level of gamma-glutamyl transferase was also associated with reduced odds of any improvement (P = .003).ConclusionsOne-third of children with NAFLD enrolled in placebo groups of clinical trials had histologic features of progression within 2 years, in association with increasing obesity and serum levels of aminotransferases and loss of glucose homeostasis
In Children With Nonalcoholic Fatty Liver Disease, Cysteamine Bitartrate Delayed Release Improves Liver Enzymes but Does Not Reduce Disease Activity Scores
Background & aimsNo treatment for nonalcoholic fatty liver disease (NAFLD) has been approved by regulatory agencies. We performed a randomized controlled trial to determine whether 52 weeks of cysteamine bitartrate delayed release (CBDR) reduces the severity of liver disease in children with NAFLD.MethodsWe performed a double-masked trial of 169 children with NAFLD activity scores of 4 or higher at 10 centers. From June 2012 to January 2014, the patients were assigned randomly to receive CBDR or placebo twice daily (300 mg for patients weighing ≤65 kg, 375 mg for patients weighing >65 to 80 kg, and 450 mg for patients weighing >80 kg) for 52 weeks. The primary outcome from the intention-to-treat analysis was improvement in liver histology over 52 weeks, defined as a decrease in the NAFLD activity score of 2 points or more without worsening fibrosis; patients without biopsy specimens from week 52 (17 in the CBDR group and 6 in the placebo group) were considered nonresponders. We calculated the relative risks (RR) of improvement using a stratified Cochran-Mantel-Haenszel analysis.ResultsThere was no significant difference between groups in the primary outcome (28% of children in the CBDR group vs 22% in the placebo group; RR, 1.3; 95% confidence interval [CI], 0.8-2.1; P = .34). However, children receiving CBDR had significant changes in prespecified secondary outcomes: reduced mean levels of alanine aminotransferase (reduction, 53 ± 88 U/L vs 8 ± 77 U/L in the placebo group; P = .02) and aspartate aminotransferase (reduction, 31 ± 52 vs 4 ± 36 U/L in the placebo group; P = .008), and a larger proportion had reduced lobular inflammation (36% in the CBDR group vs 21% in the placebo group; RR, 1.8; 95% CI, 1.1-2.9; P = .03). In a post hoc analysis of children weighing 65 kg or less, those taking CBDR had a 4-fold better chance of histologic improvement (observed in 50% of children in the CBDR group vs 13% in the placebo group; RR, 4.0; 95% CI, 1.3-12.3; P = .005).ConclusionsIn a randomized trial, we found that 1 year of CBDR did not reduce overall histologic markers of NAFLD compared with placebo in children. Children receiving CBDR, however, had significant reductions in serum aminotransferase levels and lobular inflammation. ClinicalTrials.gov no: NCT01529268