RESUMO
OBJECTIVE: To investigate the prevalence and characteristics of children with nonalcoholic fatty liver disease (NAFLD) who reduce their body mass index (BMI) z-score (BMIz) by >.25, a goal in obesity medicine, and to determine the BMIz decrease needed for serum aminotransferase normalization. STUDY DESIGN: This retrospective, single-center study included patients aged <18 years followed for NAFLD. Patients who had undergone weight loss surgery or had other reasons for weight loss/gain were excluded. Logistic regression was used to determine the odds of achieving a BMIz change of >-.25, as well as predictors of this outcome. RESULTS: Of the 784 children who met the study criteria (median age, 13 years; 66% male; 24% Hispanic), 541 had a lowest BMIz at >90 days following the baseline clinic visit. Of these children, 168 (31%) had a BMIz change of >-.25 from baseline over a median of 367 days (IQR, 201-678 days). Decreases in serum aminotransferase and lipid levels were seen in both groups (with and without a BMIz change of >-.25); however, these decreases were more pronounced in children who achieved a BMIz drop of >.25. Hemoglobin A1c concentration did not change in either group. Young age (OR, .861; 95% CI, .81-.92; P < .01) and non-Hispanic ethnicity (OR of non-Hispanic vs Hispanic, .61; 95% CI, .38-.97; P < .04) were predictors of a BMIz change >-.25. The BMIz decrease associated with normalization of serum alanine aminotransferase was .27. CONCLUSIONS: A BMIz reduction of >.25 is associated with significant changes in serum aminotransferase levels. These findings can further guide the clinical management of children with NAFLD.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Criança , Masculino , Adolescente , Feminino , Índice de Massa Corporal , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Estudos Retrospectivos , Alanina Transaminase , Hispânico ou Latino , Aumento de PesoRESUMO
OBJECTIVE: To investigate the association between muscle mass and liver disease severity in pediatric patients with non-alcoholic fatty liver disease (NAFLD). STUDY DESIGN: This was a retrospective study of patients aged <20 years followed from 2009 to 2018. Muscle mass was estimated in all patients by measuring magnetic resonance imaging-based total psoas muscle surface area (tPMSA) and correcting for height (tPMSA index = tPMSA/height2). Two cohorts were studied, one with histological confirmation of NAFLD (n = 100) and the other with magnetic resonance imaging (MRI) evidence of hepatic steatosis (n = 236). Histology was scored using Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) criteria. MRI-measured proton density fat fraction (PDFF) and liver stiffness were collected. Demographic, clinical, and socioeconomic status (using a validated Community Deprivation Index [CDI]) were assessed as covariates. Univariate regression analyses, followed by multivariable regression analyses, were used to determine the relationships between tPMSA index and NAS, MRI-PDFF, and liver stiffness, adjusting for clinical, demographic, and CDI variables. RESULTS: In the multivariable regression analyses, higher steatosis score was associated with a lower tPMSA index (OR, 0.73; 95% CI, 0.56-0.96) and younger age (OR, 0.84; 95% CI, 0.73-0.97). Liver PDFF was also significantly associated with the tPMSA index (P = .029), sex (P = .019), and CDI (P = .005). In contrast, liver stiffness was not associated with tPMSA in multivariable analyses. CONCLUSIONS: tPMSA index was independently associated with both imaging and histological features of hepatic steatosis severity in children. Future studies should directly explore the presence and directionality of causative links between muscle mass and steatosis, as well as whether interventions that enhance muscle mass can reduce disease severity in children with NAFLD.
Assuntos
Hepatopatia Gordurosa não Alcoólica/patologia , Músculos Psoas/patologia , Sarcopenia/diagnóstico , Adolescente , Adulto , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Músculos Psoas/diagnóstico por imagem , Estudos Retrospectivos , Sarcopenia/etiologia , Sarcopenia/patologia , Índice de Gravidade de Doença , Adulto JovemRESUMO
OBJECTIVES: To determine the prevalence of renal impairment in a large cohort of youths with histologically confirmed nonalcoholic fatty liver disease (NAFLD), and to determine its association with liver disease severity. STUDY DESIGN: Clinical, laboratory, and histology data were collected retrospectively in a pediatric cohort with biopsy-confirmed NAFLD at a tertiary care center between 2010 and 2017. Histological NAFLD severity was scored using validated criteria. Glomerular filtration rate (GFR) was calculated and categorized as low (<90 mL/min/1.73 m2), normal (90-136 mL/min/1.73 m2), or high (>136 mL/min/1.73 m2). Univariate and multivariate modeling were used to determine differences between the GFR groups and to control for confounders. RESULTS: The cohort comprised 179 patients (82% non-Hispanic; median age; 14 years; IQR, 12-16 years). One-third of the patients had abnormal renal function, including 36 (20%) with glomerular hyperfiltration and 26 (15%) with low GFR. In multivariable logistic regression, compared with normal GFR, hyperfiltration was independently associated with higher NAFLD activity score (aOR, 2.96; 95% CI, 1.49-5.87; P = .002), after adjusting for age, sex, ethnicity, obesity severity, presence of type 2 diabetes mellitus, and medications. CONCLUSIONS: In this large cohort with histologically confirmed NAFLD, renal impairment was highly prevalent and associated with liver disease severity, independent of obesity severity. Screening patients with confirmed NAFLD for renal complication is recommended.
Assuntos
Taxa de Filtração Glomerular , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Adolescente , Criança , Feminino , Humanos , Hepatopatias/etiologia , Hepatopatias/fisiopatologia , Masculino , Hepatopatia Gordurosa não Alcoólica/complicações , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
OBJECTIVES: To test whether follow-up testing for very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency uncovers a diagnosis in patients with elevations of C14:1 and C14:2 plasma acylcarnitines after a controlled fasting study performed for clinically suspected hypoglycemia and to compare the acylcarnitine profiles from fasted patients without VLCAD deficiency vs patients with known VLCAD deficiency to determine whether metabolite testing distinguishes these groups. STUDY DESIGN: We performed a retrospective chart review and identified 17 patients with elevated C14:1 and C14:2 plasma acylcarnitine levels after a controlled fast and with testing for VLCAD deficiency (ACADVL sequencing or fibroblast fatty acid oxidation studies). The follow-up testing in all patients was inconsistent with a diagnosis of VLCAD deficiency. We compared the plasma acylcarnitine profiles from these fasted patients vs patients with VLCAD deficiency. RESULTS: C14:1/C12:1 was significantly lower (P < .001) in fasted patients vs patients with VLCAD deficiency. Metabolomics analysis performed in 2 fasted patients and 1 patient with VLCAD deficiency demonstrated evidence for up-regulated lipolysis and ß-oxidation in the fasted state. CONCLUSIONS: Elevations of plasma C14:1 and C14:2 acylcarnitines appear to be a physiologic result of lipolysis that occurs with fasting. Both metabolomics analysis and/or C14:1/C12:1 may distinguish C14:1 elevations from physiologic fasting-induced lipolysis vs VLCAD deficiency.
Assuntos
Acil-CoA Desidrogenase de Cadeia Longa/deficiência , Carnitina/análogos & derivados , Jejum/sangue , Erros Inatos do Metabolismo Lipídico/sangue , Erros Inatos do Metabolismo Lipídico/diagnóstico , Doenças Mitocondriais/sangue , Doenças Mitocondriais/diagnóstico , Doenças Musculares/sangue , Doenças Musculares/diagnóstico , Acil-CoA Desidrogenase de Cadeia Longa/sangue , Adolescente , Carnitina/sangue , Criança , Pré-Escolar , Síndrome Congênita de Insuficiência da Medula Óssea , Feminino , Humanos , Lactente , Masculino , Estudos RetrospectivosRESUMO
BACKGROUND: To better understand the neural tube defect (NTD) causal pathway, the authors measured homocysteine, an indicator of tissue micronutrient deficiencies. The authors examined independent and joint associations of serum homocysteine, B12, and folate and red blood cell (RBC) folate with NTD-affected pregnancies. METHODS: Case women in this population-based study had NTD-affected pregnancies and resided and delivered in one of the 14 Texas-Mexico border counties from 1995 through 2000. Control women were study area residents delivering normal live births during the same period. The authors measured homocysteine levels using tandem mass spectroscopy; competitive binding was used for other biomarkers. RESULTS: Homocysteine testing was done on 103 cases and 139 controls. Odds ratios (ORs) were increased in all upper homocysteine quintiles compared to the lowest quintile (1.7, 1.3, 2.8, 2.4). Women with high homocysteine values had increased ORs regardless of high versus low levels for B12 (OR = 3.5, 4.8, respectively) or RBC folate (OR = 2.9, 3.5, respectively). CONCLUSIONS: High serum homocysteine levels are associated with NTD-affected pregnancies. Moreover, high homocysteine levels have a detrimental effect on NTD-risk even when serum B12 or RBC folate levels are high. Excess homocysteine might play an independent role in the development of NTDs.