Non-Invasive Approaches to Estimate Liver Steatosis and Stiffness in Children With Non-Alcoholic Fatty Liver Disease.
Journal
Journal of pediatric gastroenterology and nutrition
ISSN: 1536-4801
Titre abrégé: J Pediatr Gastroenterol Nutr
Pays: United States
ID NLM: 8211545
Informations de publication
Date de publication:
01 04 2022
01 04 2022
Historique:
pubmed:
16
12
2021
medline:
18
6
2022
entrez:
15
12
2021
Statut:
ppublish
Résumé
To develop pediatric-specific models that predict liver stiffness and hepatic steatosis in non-alcoholic fatty liver disease (NAFLD), based on clinical and laboratory data. Children with NAFLD, who had undergone magnetic resonance imaging with proton density fat fraction (MRI-PDFF) for steatosis quantification and/or magnetic resonance elastography (MRE) for liver stiffness assessment were included. We used data from patients imaged between April 2009 to July 2018 to develop a predictive model for fat fraction and stiffness. We validated the performance of the models using data from a second cohort, imaged between 2018 and 2019. The first cohort (n = 344) consisted of predominantly non-Hispanic (80%), male (67%) adolescents. MRE data were available for 343 children, while PDFF data were available for 130. In multivariable regression, ethnicity, insulin levels, platelet count, and aspartate aminotransferase independently predicted liver stiffness and these variables were used to develop the predictive model. Similarly, sex, ethnicity, alanine aminotransferase, and triglycerides levels independently predicted liver PDFF and were used in the PDFF model. The AUC of the optimal cutoff for the model that predicted a stiffness of >2.71 kPa was 0.70 and for the model that predicted PDFF >5% was 0.78. The validation group (n = 110) had similar characteristics. The correlation coefficient of the model with the measured liver stiffness was 0.30 and with the measured liver PDFF was 0.26. Pediatric-specific models perform poorly at predicting exact liver stiffness and steatosis; however, in the absence of magnetic resonance imaging can be used to predict the presence of significant steatosis (>5%) and/or significant stiffness (>2.71). Thus, imaging remains an invaluable adjunct to laboratory investigations in determining disease severity.
Identifiants
pubmed: 34908012
doi: 10.1097/MPG.0000000000003371
pii: 00005176-202204000-00014
pmc: PMC9673005
mid: NIHMS1843500
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
495-502Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK078392
Pays : United States
Informations de copyright
Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest.
Références
Anderson EL, Howe LD, Jones HE, et al. The prevalence of non-alcoholic fatty liver disease in children and adolescents: a systematic review and meta-analysis. PLoS One 2015; 10: e0140908.
Dhaliwal J, Chavhan GB, Lurz E, et al. Hepatic steatosis is highly prevalent across the paediatric age spectrum, including in pre-school age children. Aliment Pharmacol Ther 2018; 48:556–563.
Xanthakos SA, Trout AT, Dillman JR. Magnetic resonance elastography assessment of fibrosis in children with NAFLD: promising but not perfect. Hepatology 2017; 66:1373–1376.
Dillman JR, Trout AT, Costello EN, et al. Quantitative liver MRI-biopsy correlation in pediatric and young adult patients with nonalcoholic fatty liver disease: can one be used to predict the other? AJR Am J Roentgenol 2018; 210:166–174.
Xanthakos SA, Podberesky DJ, Serai SD, et al. Use of magnetic resonance elastography to assess hepatic fibrosis in children with chronic liver disease. J Pediatr 2014; 164:186–188.
Mouzaki M, Ling SC, Schreiber RA, et al. Management of pediatric nonalcoholic fatty liver disease by academic hepatologists in Canada: a nationwide survey. J Pediatr Gastroenterol Nutr 2017; 65:380–383.
Diehl AM, Day C. Cause, pathogenesis, and treatment of nonalcoholic steatohepatitis. N Engl J Med 2017; 377:2063–2072.
Vos MB, Abrams SH, Barlow SE, et al. NASPGHAN clinical practice guideline for the diagnosis and treatment of nonalcoholic fatty liver disease in children: recommendations from the Expert Committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). J Pediatr Gastroenterol Nutr 2017; 64:319–334.
Browning JD, Szczepaniak LS, Dobbins R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004; 40:1387–1395.
Molleston JP, Schwimmer JB, Yates KP, et al. Histological abnormalities in children with nonalcoholic fatty liver disease and normal or mildly elevated alanine aminotransferase levels. J Pediatr 2014; 164: 707–13 e3.
Orkin S, Yodoshi T, Sun Q, et al. Can baseline characteristics be used to predict liver disease outcomes in pediatric nonalcoholic fatty liver disease? Obesity (Silver Spring) 2020; 29:171–176.
Permutt Z, Le TA, Peterson MR, et al. Correlation between liver histology and novel magnetic resonance imaging in adult patients with non-alcoholic fatty liver disease—MRI accurately quantifies hepatic steatosis in NAFLD. Aliment Pharmacol Ther 2012; 36:22–29.
Middleton MS, Heba ER, Hooker CA, et al. Agreement between magnetic resonance imaging proton density fat fraction measurements and pathologist-assigned steatosis grades of liver biopsies from adults with nonalcoholic steatohepatitis. Gastroenterology 2017; 153:753–761.
Younossi ZM, Loomba R, Anstee QM, et al. Diagnostic modalities for nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and associated fibrosis. Hepatology 2018; 68:349–360.
Middleton MS, Van Natta ML, Heba ER, et al. Diagnostic accuracy of magnetic resonance imaging hepatic proton density fat fraction in pediatric nonalcoholic fatty liver disease. Hepatology 2018; 67:858–872.
Angulo P, Kleiner DE, Dam-Larsen S, et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology 2015; 149:389.e10–397.e10.
Loaeza-del-Castillo A, Paz-Pineda F, Oviedo-Cárdenas E, et al. AST to platelet ratio index (APRI) for the noninvasive evaluation of liver fibrosis. Ann Hepatol 2008; 7:350–357.
Nobili V, Alisi A, Vania A, et al. The pediatric NAFLD fibrosis index: a predictor of liver fibrosis in children with non-alcoholic fatty liver disease. BMC Med 2009; 7:21.
Alkhouri N, Mansoor S, Giammaria P, et al. The development of the pediatric NAFLD fibrosis score (PNFS) to predict the presence of advanced fibrosis in children with nonalcoholic fatty liver disease. PLoS One 2014; 9:e104558.
Vallet-Pichard A, Mallet V, Nalpas B, et al. FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. comparison with liver biopsy and fibrotest. Hepatology 2007; 46:32–36.
Kotronen A, Peltonen M, Hakkarainen A, et al. Prediction of non-alcoholic fatty liver disease and liver fat using metabolic and genetic factors. Gastroenterology 2009; 137:865–872.
Mouzaki M, Trout AT, Arce-Clachar AC, et al. Assessment of nonalcoholic fatty liver disease progression in children using magnetic resonance imaging. J Pediatr 2018; 201:86–92.
Yodoshi T, Orkin S, Arce-Clachar AC, et al. Alternative etiologies of liver disease in children with suspected NAFLD. Pediatrics 2021; 147:e009829.
Krebs NF, Himes JH, Jacobson D, et al. Assessment of child and adolescent overweight and obesity. Pediatrics 2007; 120: (Suppl 4): S193–S228.
Koot BG, van der Baan-Slootweg OH, Bohte AE, et al. Accuracy of prediction scores and novel biomarkers for predicting nonalcoholic fatty liver disease in obese children. Obesity (Silver Spring) 2013; 21:583–590.
Schwimmer JB, Behling C, Angeles JE, et al. Magnetic resonance elastography measured shear stiffness as a biomarker of fibrosis in pediatric nonalcoholic fatty liver disease. Hepatology 2017; 66:1474–1485.
Jackson JA, Konomi JV, Mendoza MV, et al. Performance of fibrosis prediction scores in paediatric non-alcoholic fatty liver disease. J Paediatr Child Health 2018; 54:172–176.
Neuschwander-Tetri BA, Clark JM, Bass NM, et al. Clinical, laboratory and histological associations in adults with nonalcoholic fatty liver disease. Hepatology 2010; 52:913–924.
Bambha K, Belt P, Abraham M, et al. Ethnicity and nonalcoholic fatty liver disease. Hepatology 2012; 55:769–780.
Patton HM, Yates K, Unalp-Arida A, et al. Association between metabolic syndrome and liver histology among children with nonalcoholic Fatty liver disease. Am J Gastroenterol 2010; 105:2093–2102.
Xanthakos SA, Jenkins TM, Kleiner DE, et al. High prevalence of nonalcoholic fatty liver disease in adolescents undergoing bariatric surgery. Gastroenterology 2015; 149:623.e8–634.e8.
Awai HI, Newton KP, Sirlin CB, et al. Evidence and recommendations for imaging liver fat in children, based on systematic review. Clin Gastroenterol Hepatol 2014; 12:765–773.
Romeo S, Kozlitina J, Xing C, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2008; 40:1461–1465.
Donnelly KL, Smith CI, Schwarzenberg SJ, et al. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 2005; 115:1343–1351.
Ballestri S, Nascimbeni F, Baldelli E, et al. NAFLD as a sexual dimorphic disease: role of gender and reproductive status in the development and progression of nonalcoholic fatty liver disease and inherent cardiovascular risk. Adv Ther 2017; 34:1291–1326.
Sahota AK, Shapiro WL, Newton KP, et al. Incidence of nonalcoholic fatty liver disease in children: 2009–2018. Pediatrics 2020; 146:e20200771.
Cassinotto C, Boursier J, de Ledinghen V, et al. Liver stiffness in nonalcoholic fatty liver disease: a comparison of supersonic shear imaging, FibroScan, and ARFI with liver biopsy. Hepatology 2016; 63:1817–1827.
Tokuhara D, Cho Y, Shintaku H. Transient elastography-based liver stiffness age-dependently increases in children. PLoS One 2016; 11:e0166683.
Joshi M, Dillman JR, Singh K, et al. Quantitative MRI of fatty liver disease in a large pediatric cohort: correlation between liver fat fraction, stiffness, volume, and patient-specific factors. Abdom Radiol (NY) 2018; 43:1168–1179.