Clinical correlates of histopathology in pediatric nonalcoholic steatohepatitis (NASH)

Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN)

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Abstract

Background & Aims - Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in American children. Noninvasive means to discriminate between NAFLD and nonalcoholic steatohepatitis (NASH) might diminish requirement for liver biopsy or predict those at increased risk for progression. Methods - Data obtained prospectively from children (aged 6-17 yrs) enrolled in the NASH Clinical Research Network (NASH CRN) were analyzed to identify clinical-pathological correlates of pediatric NAFLD. All participants underwent liver biopsy within 6 months of clinical data that was reviewed by a central pathology committee. Results - 176 children (mean age 12.4 years, 77% male) were eligible for inclusion. Using ordinal logistic regression analysis, increasing AST (OR 1.017 per U/L, 95% CI 1.004-1.031) and GGT (OR 1.016 per U/L, 95% CI 1.000-1.033) were independently associated with increasing severity of NASH. Increasing AST (OR 1.015 per U/L, 95% CI 1.006-1.024), increasing white blood cell count (OR 1.22 per 1000/mm3, 95% CI 1.07-1.38), and decreasing hematocrit (OR 0.87 per %, 95% CI 0.79-0.96) were independently associated with increasing severity of fibrosis. Area under the ROC for a model with AST and ALT was 0.75 (95% CI=0.66-0.84) and 0.74 (95% CI 0.63-0.85) for distinguishing steatosis from more advanced forms of NASH and bridging fibrosis from lesser degrees of fibrosis, respectively. Conclusions - Certain components of routine laboratory tests are predictive of NAFLD pattern and fibrosis severity, but do not have adequate discriminate power to replace liver biopsy in evaluating pediatric NAFLD.

Original languageEnglish (US)
JournalGastroenterology
Volume135
Issue number6
DOIs
StatePublished - Dec 1 2008

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Pediatrics
Fibrosis
Biopsy
Liver
Non-alcoholic Fatty Liver Disease
Leukocyte Count
Hematocrit
Liver Cirrhosis
Liver Diseases
Logistic Models
Regression Analysis
Pathology
Research

ASJC Scopus subject areas

  • Gastroenterology

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Clinical correlates of histopathology in pediatric nonalcoholic steatohepatitis (NASH). / Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN).

In: Gastroenterology, Vol. 135, No. 6, 01.12.2008.

Research output: Contribution to journalArticle

Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN). / Clinical correlates of histopathology in pediatric nonalcoholic steatohepatitis (NASH). In: Gastroenterology. 2008 ; Vol. 135, No. 6.
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abstract = "Background & Aims - Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in American children. Noninvasive means to discriminate between NAFLD and nonalcoholic steatohepatitis (NASH) might diminish requirement for liver biopsy or predict those at increased risk for progression. Methods - Data obtained prospectively from children (aged 6-17 yrs) enrolled in the NASH Clinical Research Network (NASH CRN) were analyzed to identify clinical-pathological correlates of pediatric NAFLD. All participants underwent liver biopsy within 6 months of clinical data that was reviewed by a central pathology committee. Results - 176 children (mean age 12.4 years, 77{\%} male) were eligible for inclusion. Using ordinal logistic regression analysis, increasing AST (OR 1.017 per U/L, 95{\%} CI 1.004-1.031) and GGT (OR 1.016 per U/L, 95{\%} CI 1.000-1.033) were independently associated with increasing severity of NASH. Increasing AST (OR 1.015 per U/L, 95{\%} CI 1.006-1.024), increasing white blood cell count (OR 1.22 per 1000/mm3, 95{\%} CI 1.07-1.38), and decreasing hematocrit (OR 0.87 per {\%}, 95{\%} CI 0.79-0.96) were independently associated with increasing severity of fibrosis. Area under the ROC for a model with AST and ALT was 0.75 (95{\%} CI=0.66-0.84) and 0.74 (95{\%} CI 0.63-0.85) for distinguishing steatosis from more advanced forms of NASH and bridging fibrosis from lesser degrees of fibrosis, respectively. Conclusions - Certain components of routine laboratory tests are predictive of NAFLD pattern and fibrosis severity, but do not have adequate discriminate power to replace liver biopsy in evaluating pediatric NAFLD.",
author = "{Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN)} and Heather Patton and Lavine, {Joel E.} and {Van Natta}, {Mark L.} and Schwimmer, {Jeffrey B.} and David Kleiner and Jean Molleston and Arthur McCullough and Margaret Stager and Ariel Feldstein and Diehl, {Anna Mae} and Ann Scheimann and Naga Chalasani and Girish Subbarao and Brent Tetri and Sarah Barlow and Stephanie Abrams and Nathan Bass and Philip Rosenthal and Kris Kowdley and Karen Murray and Arun Sanyal and Daphne Bryan and James Tonascia and Patricia Robuck and Jay Hoofnagle and Terry Huang",
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AU - Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN)

AU - Patton, Heather

AU - Lavine, Joel E.

AU - Van Natta, Mark L.

AU - Schwimmer, Jeffrey B.

AU - Kleiner, David

AU - Molleston, Jean

AU - McCullough, Arthur

AU - Stager, Margaret

AU - Feldstein, Ariel

AU - Diehl, Anna Mae

AU - Scheimann, Ann

AU - Chalasani, Naga

AU - Subbarao, Girish

AU - Tetri, Brent

AU - Barlow, Sarah

AU - Abrams, Stephanie

AU - Bass, Nathan

AU - Rosenthal, Philip

AU - Kowdley, Kris

AU - Murray, Karen

AU - Sanyal, Arun

AU - Bryan, Daphne

AU - Tonascia, James

AU - Robuck, Patricia

AU - Hoofnagle, Jay

AU - Huang, Terry

PY - 2008/12/1

Y1 - 2008/12/1

N2 - Background & Aims - Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in American children. Noninvasive means to discriminate between NAFLD and nonalcoholic steatohepatitis (NASH) might diminish requirement for liver biopsy or predict those at increased risk for progression. Methods - Data obtained prospectively from children (aged 6-17 yrs) enrolled in the NASH Clinical Research Network (NASH CRN) were analyzed to identify clinical-pathological correlates of pediatric NAFLD. All participants underwent liver biopsy within 6 months of clinical data that was reviewed by a central pathology committee. Results - 176 children (mean age 12.4 years, 77% male) were eligible for inclusion. Using ordinal logistic regression analysis, increasing AST (OR 1.017 per U/L, 95% CI 1.004-1.031) and GGT (OR 1.016 per U/L, 95% CI 1.000-1.033) were independently associated with increasing severity of NASH. Increasing AST (OR 1.015 per U/L, 95% CI 1.006-1.024), increasing white blood cell count (OR 1.22 per 1000/mm3, 95% CI 1.07-1.38), and decreasing hematocrit (OR 0.87 per %, 95% CI 0.79-0.96) were independently associated with increasing severity of fibrosis. Area under the ROC for a model with AST and ALT was 0.75 (95% CI=0.66-0.84) and 0.74 (95% CI 0.63-0.85) for distinguishing steatosis from more advanced forms of NASH and bridging fibrosis from lesser degrees of fibrosis, respectively. Conclusions - Certain components of routine laboratory tests are predictive of NAFLD pattern and fibrosis severity, but do not have adequate discriminate power to replace liver biopsy in evaluating pediatric NAFLD.

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DO - 10.1053/j.gastro.2008.08.050

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