TY - JOUR
T1 - Relationship of Enhanced Liver Fibrosis Score with Pediatric Nonalcoholic Fatty Liver Disease Histology and Response to Vitamin E or Metformin
AU - Gawrieh, Samer
AU - Harlow, Kathryn E.
AU - Pike, Francis
AU - Yates, Katherine P.
AU - Wilson, Laura A.
AU - Cummings, Oscar W.
AU - Rosenberg, William M.
AU - Chalasani, Naga
AU - Molleston, Jean P.
N1 - Funding Information:
This study was approved by the National Institute of Diabetes and Digestive and Kidney Diseases funded Nonalcoholic Steatohepatitis Clinical Research Network as an Ancillary Study (NASH CRN AS #063). The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) is supported by the National Institute of Diabetes and Digestive and Kidney Diseases ( U01DK061713 , U01DK061718 , U01DK061728 , U01DK061731 , U01DK061732 , U01DK061734 , U01DK061737 , U01DK061738 , U01DK061730 , and U24DK061730 ). Biosamples and phenotype and histologic data were provided by the NASH CRN. ELF measurements were conducted in a blinded fashion by Siemens. Siemens or its designees had no role in data analysis or article preparation. The final manuscript was provided to Siemens before its submission for their comments. The TONIC trial was conducted by the NASH CRN and supported in part by the Intramural Research Program of the National Cancer Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development . The vitamin E and matching placebo were provided by Pharmavite through a Clinical Trial Agreement with the National Institutes of Health. S.G. serves as a consultant for TransMedics and Pfizer; and receives research grant support from Cirius , Galmed , Viking , and Zydus . O.C. reports a service contract with Novo-Nordisk. W.R. serves as a consultant for Siemens Healthineers, Gilead Sciences, and GSK. N.G. reports ongoing research support from Eli Lilly , Galectin Therapeutics , Intercept , and Exact Sciences and has received consulting fees from Abbvie, Madrigal, Nusirt, Allergan, Siemens, Genentech, Zydus, La Jolla, Axcella, Foresite Labs, and Galectin Therapeutics. J.M. reports ongoing research support from Albireo , Abbvie , Gillead , Mirum , and the CF Foundation . The other authors declare no conflicts of interest.
Funding Information:
This study was approved by the National Institute of Diabetes and Digestive and Kidney Diseases funded Nonalcoholic Steatohepatitis Clinical Research Network as an Ancillary Study (NASH CRN AS #063). The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (U01DK061713, U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, and U24DK061730). Biosamples and phenotype and histologic data were provided by the NASH CRN. ELF measurements were conducted in a blinded fashion by Siemens. Siemens or its designees had no role in data analysis or article preparation. The final manuscript was provided to Siemens before its submission for their comments. The TONIC trial was conducted by the NASH CRN and supported in part by the Intramural Research Program of the National Cancer Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The vitamin E and matching placebo were provided by Pharmavite through a Clinical Trial Agreement with the National Institutes of Health. S.G. serves as a consultant for TransMedics and Pfizer; and receives research grant support from Cirius, Galmed, Viking, and Zydus. O.C. reports a service contract with Novo-Nordisk. W.R. serves as a consultant for Siemens Healthineers, Gilead Sciences, and GSK. N.G. reports ongoing research support from Eli Lilly, Galectin Therapeutics, Intercept, and Exact Sciences and has received consulting fees from Abbvie, Madrigal, Nusirt, Allergan, Siemens, Genentech, Zydus, La Jolla, Axcella, Foresite Labs, and Galectin Therapeutics. J.M. reports ongoing research support from Albireo, Abbvie, Gillead, Mirum, and the CF Foundation. The other authors declare no conflicts of interest. Funding and disclosure information is available at www.jpeds.com.
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/12
Y1 - 2021/12
N2 - Objectives: To study the diagnostic performance of the enhanced liver fibrosis score (ELF) for detecting different stages of fibrosis and its usefulness in detecting histologic response to vitamin E or metformin in children with nonalcoholic fatty liver disease who participated in the Vitamin E or Metformin for the Treatment Of NAFLD In Children (TONIC) trial. Study design: ELF was measured at baseline and weeks 24, 48, and 96 on sera from 166 TONIC participants. Associations between ELF with baseline and end of trial (EOT) fibrosis stages and other histologic features were assessed using χ2 tests and logistic regression models. Results: ELF was significantly associated with severity of fibrosis at baseline and EOT. ELF areas under the curve for discriminating patients with clinically significant and advanced fibrosis were 0.70 (95% CI, 0.60-0.80) and 0.79 (95% CI, 0.69-0.89), respectively. A 1-unit decrease in ELF at EOT was associated with overall histologic improvement (OR, 1.86; 95% CI, 1.11-3.14; P = .02), resolution of steatohepatitis (OR, 1.88; 95% CI, 1.09-3.25; P = .02), improvement in steatosis grade (OR, 1.76; 95% CI, 1.06-2.82; P = .03), and hepatocellular ballooning (OR, 1.79; 95% CI, 1.06-3.00; P = .03), but not with improvement in fibrosis stage (OR, 1.26; 95% CI, 0.78-2.03; P = .34). Conclusions: ELF was associated with fibrosis stage in children who participated in TONIC. Although not associated with improvement in fibrosis, a decrease in ELF at EOT was associated with Nonalcoholic Steatohepatitis resolution and improvement in nonalcoholic fatty liver disease histology. ELF may be a useful noninvasive test to monitor treatment response in children with nonalcoholic fatty liver disease.
AB - Objectives: To study the diagnostic performance of the enhanced liver fibrosis score (ELF) for detecting different stages of fibrosis and its usefulness in detecting histologic response to vitamin E or metformin in children with nonalcoholic fatty liver disease who participated in the Vitamin E or Metformin for the Treatment Of NAFLD In Children (TONIC) trial. Study design: ELF was measured at baseline and weeks 24, 48, and 96 on sera from 166 TONIC participants. Associations between ELF with baseline and end of trial (EOT) fibrosis stages and other histologic features were assessed using χ2 tests and logistic regression models. Results: ELF was significantly associated with severity of fibrosis at baseline and EOT. ELF areas under the curve for discriminating patients with clinically significant and advanced fibrosis were 0.70 (95% CI, 0.60-0.80) and 0.79 (95% CI, 0.69-0.89), respectively. A 1-unit decrease in ELF at EOT was associated with overall histologic improvement (OR, 1.86; 95% CI, 1.11-3.14; P = .02), resolution of steatohepatitis (OR, 1.88; 95% CI, 1.09-3.25; P = .02), improvement in steatosis grade (OR, 1.76; 95% CI, 1.06-2.82; P = .03), and hepatocellular ballooning (OR, 1.79; 95% CI, 1.06-3.00; P = .03), but not with improvement in fibrosis stage (OR, 1.26; 95% CI, 0.78-2.03; P = .34). Conclusions: ELF was associated with fibrosis stage in children who participated in TONIC. Although not associated with improvement in fibrosis, a decrease in ELF at EOT was associated with Nonalcoholic Steatohepatitis resolution and improvement in nonalcoholic fatty liver disease histology. ELF may be a useful noninvasive test to monitor treatment response in children with nonalcoholic fatty liver disease.
KW - ELF
KW - NASH
KW - PIIINP
KW - metformin
KW - vitamin E
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UR - http://www.scopus.com/inward/citedby.url?scp=85114677275&partnerID=8YFLogxK
U2 - 10.1016/j.jpeds.2021.08.012
DO - 10.1016/j.jpeds.2021.08.012
M3 - Article
C2 - 34400208
AN - SCOPUS:85114677275
SN - 0022-3476
VL - 239
SP - 161-167.e5
JO - Journal of Pediatrics
JF - Journal of Pediatrics
ER -