1,720,998 research outputs found
A non-invasive prediction model for non-alcoholic steatohepatitis in paediatric patients with non-alcoholic fatty liver disease
No full textBackground: Non-alcoholic fatty liver disease encompasses a spectrum of diseases that range from simple steatosis to the aggressive form of non-alcoholic steatohepatitis. Non-alcoholic steatohepatitis is currently diagnosed through liver biopsy. Aim: To develop a non-invasive predictive model of non-alcoholic steatohepatitis in children with non-alcoholic fatty liver disease. Methods: Anthropometric, laboratory, and histologic data were obtained in a cohort of children with biopsy-proven non-alcoholic fatty liver disease. Multivariable logistic regression analysis was employed to create a nomogram predicting the risk of non-alcoholic steatohepatitis. Internal validation was performed by bootstrapping. Results: Three hundred and two children were included in this analysis with a mean age of 12.3. ±. 3.1 years, a mean body mass index percentile of 94.3. ±. 6.9, and non-alcoholic steatohepatitis was present in 67%. Following stepwise variable selection, total cholesterol, waist circumference percentile, and total bilirubin were included as variables in the model, with good discrimination with an area under the receiver operating characteristic curve of 0.737. Conclusions: A nomogram was constructed with reasonable accuracy that can predict the risk of non-alcoholic steatohepatitis in children with non-alcoholic fatty liver disease. If validated externally, this tool could be utilized as a non-invasive method to diagnose non-alcoholic steatohepatitis in children with non-alcoholic fatty liver disease
Non-high-density lipoprotein cholesterol (non-HDL-C) levels in children with nonalcoholic fatty liver disease (NAFLD)
Full text linkNon-alcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular disease (CVD) risk in children. Non-high density lipoprotein-cholesterol (non-HDL-C) has been shown to be a good predictor of cardiovascular events. Recent data in adults found non-alcoholic steatohepatitis (NASH) to be associated with significantly higher levels of non-HDL-C than simple steatosis, suggestive it might be used as a non-invasive tool to diagnose NASH. The goal of our study was to assess non-HDL-C levels in children with NAFLD. Our cohort consisted of pediatric patients with biopsy-proven NAFLD. Anthropometric, laboratory, and histologic data were obtained on all patients. Univariable analysis was performed to assess differences in clinical characteristics between groups. Spearman rank correlation coefficients were calculated to assess the correlation between non-HDL-C levels and clinical variables. ANCOVA was used to adjust for possible confounders. 302 subjects with NAFLD were included in our study; 203 with NASH and 99 without NASH. Subjects with NASH had significantly higher non-HDL-C levels than those without (p = 0.004). Histologic features of NASH, including ballooning, inflammation, and fibrosis were found to be weakly correlated with non-HDL-C levels, (p < 0.05 for all). After adjusting for the presence of metabolic syndrome (MetS), ALT, and GGT, the association between non-HDL-C and NASH was not significant (p = 0.66). In Conclusion, non-HDL-C levels are higher in children with NASH than those with simple steatosis, suggesting increased CVD risk. This may be a reflection of the higher prevalence of MetS. Non-HDL-C had a positive association with histologic features of NASH. © 2014 Alkhouri et al.; licensee Springer
Low serum potassium levels associated with disease severity in children with nonalcoholic fatty liver disease
No full textPurpose: Recent studies have suggested that decreased serum potassium level may contribute to various metabolic disorders in adult patients including nonalcoholic fatty liver disease (NAFLD). We aimed to study the correlation between serum potassium levels and the histologic severity of NAFLD in children. Methods: Pediatric patients with biopsy-proven NAFLD were included in this study. Demographic, clinical, and histopathological data were obtained. Multivariable logistic regression analysis was used to assess whether potassium levels are associated with the presence of nonalcoholic steatohepatitis (NASH) or fibrosis after adjusting for possible confounders. A p-value < 0.05 was considered statistically significant. Results: Among 125 biopsies, 49.6% (62) had evidence of NASH while 66.4% (83) had some degree of fibrosis (stage 1-3). Mean serum potassium was significantly lower in NASH group as compared to non-NASH group (4.4±0.42 mmoL/L vs. 4.8±0.21, p < 0.001). Higher potassium level had negative correlation with presence of steatosis, ballooning, lobular inflammation, fibrosis and NAFLD activity score (p < 0.05). On multivariable analysis and after adjusting for the metabolic syndrome and insulin resistance, higher potassium level was significantly associated with lower likelihood of having a histological diagnosis of NASH on biopsy (odds ratio [OR], 0.12; 95% confidence interval [95% CI], 0.05-0.28; p < 0.001). Similarly, the likelihood of having fibrosis decreases by 76% for every 0.5 mmoL/L increase in potassium (OR, 0.24; 95% CI, 0.11-0.54; p < 0.001). Conclusion: Our study shows an inverse relationship between serum potassium levels and the presence of aggressive disease (NASH and fibrosis) in children with NAFLD
Serum cytokeratin-18 fragment levels are useful biomarkers for nonalcoholic steatohepatitis in children
No full textOBJECTIVES:Nonalcoholic steatohepatitis (NASH) is the most aggressive form of nonalcoholic fatty liver disease (NAFLD). Noninvasive methods to identify children with NASH are urgently needed. The aim of this study was to evaluate the use of plasma cytokeratin-18 (CK18) fragment levels, a marker of increased hepatocyte apoptosis, as a non-invasive biomarker for pediatric NASH.METHODS:Consecutive children with biopsy-proven NAFLD were included and blood samples were collected at the time of the biopsy. The diagnosis of NASH was based on Brunt's criteria. Histological features were scored: steatosis (0-3), lobular inflammation (0-3), ballooning (0-2), and portal inflammation (0-2). NAFLD activity score was calculated (0-8) and fibrosis stage was scored (0-4). We measured plasma CK18 levels using the M30-Apoptosense enzyme-linked immunosorbent assay kit.RESULTS:A total of 201 subjects were included in the study. The mean age was 10.7±2.5 years and 37% were male. NASH was diagnosed in 140 patients with a mean NAFLD activity scoring of 4.4±1.3. CK18 levels were significantly higher in subjects with NASH compared with not NASH (322.1 U/l±104.8 vs. 164.2 U/l±62, respectively; P<0.001). The risk of having NASH on liver biopsy increased with increased CK18 levels (P<0.001). For every 10 U/l increase in CK18 levels, the likelihood of having NASH increased by 70% after adjusting for multiple confounders. The performance of CK18 level for the diagnosis of NASH was excellent with an area under the receiver operating characteristics curve of 0.933.CONCLUSIONS:CK18 is a promising non-invasive biomarker for NASH in children with fatty liver disease
Retinol-Binding Protein 4: A Promising Circulating Marker of Liver Damage in Pediatric Nonalcoholic Fatty Liver Disease
No full textBackground & Aims: Noninvasive methods are needed to identify pediatric nonalcoholic fatty liver disease (NAFLD), the most frequent chronic liver disease in children and adolescents in industrialized countries. Retinol-binding protein 4 (RBP4) is an adipocytokine that has been associated with the pathogenesis of insulin resistance. We tested the serum levels of RBP4 to assess their associations with the metabolic profile and histologic features in a large well-characterized group of children with NAFLD. Methods: The study included 59 children with biopsy-proven NAFLD. Histologic analyses were performed by an experienced hepatopathologist; the NAFLD activity score and fibrosis score were calculated for each patient. RBP4 levels in serum samples were measured by an enzyme-linked immunosorbent assay analysis. Anthropometric, blood pressure, and metabolic profile analyses (including glucose tolerance, fasting glucose, insulin, and lipid panel tests) were performed on samples from all patients. Results: Decreasing levels of RBP4 were associated significantly with increasing levels of serum triglyceride. High levels of RBP4 were associated significantly with low necroinflammatory activity, a low NAFLD activity score, and a low fibrosis score. Furthermore, serum RBP4 levels decreased significantly as disease severity increased; there was a stepwise decrease in RBP4 from children with steatosis (3.8 mg/dL) to borderline nonalcoholic steatohepatitis (2.9 mg/dL) to definitive nonalcoholic steatohepatitis (1.9 mg/dL) (P < .0001). This association remained significant after adjusting for other relevant clinical variables. Conclusions: Our study shows an inverse relationship between RBP4 levels and degree of liver damage. RBP4 therefore might be a potential novel noninvasive marker of severity of pediatric NAFLD. © 2009 AGA Institute
Development and validation of a new histological score for pediatric non-alcoholic fatty liver disease
No full textBackground & Aims: Pediatric non-alcoholic fatty liver disease (NAFLD) may present with a distinct histopathological pattern characterized by the presence of predominant portal-based injury and portal inflammation (PI). We aimed at developing a new grading score for pediatric NAFLD to be used in clinical trials that takes into account the presence of PI and the weight of histological features. Methods: Our training set consisted of 203 children with biopsy-proven NAFLD. The diagnosis of non-alcoholic steatohepatitis (NASH) was based on Brunt's criteria. Histological features were scored: steatosis (0-3), lobular inflammation (0-3), ballooning (0-2), and PI (0-2). Logistic regression analysis was performed to apply weight to each feature. The new score was called the Pediatric NAFLD Histological Score or PNHS. The validation set consisted of 100 children with NAFLD. Results: The mean age of the initial cohort was 12.4 ± 3.4 years and significant fibrosis (fibrosis stage ≥2) was present in 26 patients (12.8%). NASH was diagnosed in 135 patients with a mean NAS of 4.5 ± 1.4. The mean PNHS in the NASH group was 89 ± 20.5 compared to 21.9 ± 24.5 in the "not NASH" group, p <0.001. PNHS correlated with the presence of NASH according to the pathologist's diagnosis, better than the NAFLD activity score (NAS), p = 0.011. The area under the ROC curve (AUC) for the diagnosis of NASH was 0.96 for PNHS. Similar findings were observed in the validation set with an AUC of 0.94. Conclusions: PNHS may be used for histological grading of pediatric NAFLD with excellent correlation with the presence of NASH
Combined paediatric NAFLD fibrosis index and transient elastography to predict clinically significant fibrosis in children with fatty liver disease
No full textBackground: Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of disease from simple steatosis to steatohepatitis, to fibrosis and cirrhosis. The paediatric NAFLD fibrosis index (PNFI) and transient elastography (TE) are potential noninvasive markers for fibrosis. To prospectively evaluate the performance of PNFI and TE in assessing clinically significant fibrosis in children with biopsy-proven NAFLD. Methods: Our cohort consisted of 67 consecutive children with biopsy-proven NAFLD. The stage of fibrosis was scored according to the Nonalcoholic Steatohepatitis Clinical Research Network. Fibrosis ≥ 2 was considered clinically significant. PNFI was calculated using age, waist circumference and triglycerides. TE was performed using the Fibroscan apparatus. Results: Ten patients had fibrosis stage 2-3 and 57 patients had stage 0-1. Both PNFI and TE values were significantly higher in patients with significant fibrosis (P < 0.05). The area under the receiver operating characteristic (ROC) curve for predicting significant fibrosis of PNFI and TE were 0.747 and 1.00 respectively (P = 0.005). The combined use of PNFI and TE could predict the presence or absence of clinically significant fibrosis in 98% of children with NAFLD. Conclusions: In children with NAFLD, the combination of PNFI and TE can be used to accurately assess the presence of clinically significant liver fibrosis. This will help to identify patients who should undergo liver biopsy because the confirmation of advanced fibrosis would lead to closer follow-up and screening for cirrhosis-related complications
Severity of liver injury and atherogenic lipid profile in children with nonalcoholic fatty liver disease
No full textNonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. The aim of this study was to assess the relationship between severity of liver injury and atherogenic lipid profile in a large group of children with NAFLD. A total of 118 consecutive children with biopsy-proven NAFLD were included. Patients underwent extensive metabolic profiling. The NAFLD activity and fibrosis scores showed a significant positive correlation with triglyceride/HDL, total cholesterol/HDL, and LDL/HDL ratios (p <0.05) but not with apolipoprotein B/apolipoprotein A-1 ratio (p = 0.58). After adjusting for BMI, homeostatic model assessment, impaired glucose tolerance, and presence of metabolic syndrome, both the NAFLD activity score and stage of fibrosis remained independent predictors of proatherogenic lipid profile. All lipid ratios, except for apolipoprotein B/apolipoprotein A-1, were found to be markedly higher in children with nonalcoholic steatohepatitis compared with those with simple steatosis or borderline disease (p <0.05). This study shows for the first time that in children with NAFLD, the severity of liver injury is strongly associated with the presence of a more atherogenic lipid profile, having potential significant diagnostic and therapeutic implications
Reduced lysosomal acid lipase activity – A potential role in the pathogenesis of non alcoholic fatty liver disease in pediatric patients
No full textBackground Within the spectrum of nonalcoholic fatty liver disease (NAFLD), recent evidence suggests that adult patients with nonalcoholic steatohepatitis (NASH) have significantly lower blood lysosomal acid lipase (LAL) activity than those with steatosis. This has not been studied in pediatric patients with NAFLD. Aim Investigate blood LAL activity in pediatric patients with NAFLD and assess its correlation with histological severity. Methods We collected data on consecutive children with biopsy-proven NAFLD including demographics, anthropometrics, and routine laboratory tests. The histological features were graded according to the NAFLD activity scoring proposed by Kleiner et al. Blood LAL activity was measured prospectively using Lalistat 2. Results A total of 168 children were included for analysis. Mean age was 12.6 ± 8.5 years, 60.1% were males and 52.4% had NASH. Children with significant fibrosis (stage 2–3, n = 64) had a significantly lower LAL activity compared to those with mild fibrosis (stage 0–1, n = 104). There was no significant difference in LAL activity between children with NASH compared to those without NASH. Conclusion Reduced blood LAL activity correlates with severity of liver fibrosis in children with NAFLD indicating a potential role of reduced LAL activity in the pathogenesis of NAFLD-induced fibrosis
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