. 2014 Apr;164(4):707-713.e3.

doi: 10.1016/j.jpeds.2013.10.071. Epub 2013 Dec 19.

Histological abnormalities in children with nonalcoholic fatty liver disease and normal or mildly elevated alanine aminotransferase levels

Jean P Molleston¹, Jeffrey B Schwimmer², Katherine P Yates³, Karen F Murray⁴, Oscar W Cummings⁵, Joel E Lavine⁶, Elizabeth M Brunt⁷, Ann O Scheimann⁸, Aynur Unalp-Arida³; NASH Clinical Research Network

Collaborators, Affiliations

Collaborators

NASH Clinical Research Network:
Stephanie H Abrams, Leanel Angeli Fairly, Carol Hawkins, Margaret Stager, Parvathi Mohan, Stephanie DeVore, Rohit Kohli, Kathleen Lake, Stavra Xanthakos, Joel E Lavine, Ali Mencin, Nadia Ovchinsky, Elizabeth Byam, Oscar W Cummings, Ann Klipsch, Jean P Molleston, Girish Subbarao, Caroline Devadason, Kimberly Pfeifer, Ann Scheimann, Michael Torbenson, Nanda Kerkar, Frederick Suchy, Katherine Dunne, Mark H Fishbein, Katie Jacques, Ann Quinn, Cindy Riazi, Peter F Whitington, Sarah Barlow, Jose Derdoy, Debra King, Andrea Morris, Joan Siegner, Susan Stewart, Brent A Neuschwander-Tetri, Judy Thompson, Cynthia Behling, Jennifer Collins, Janis Durelle, Anya Morgan, Steven Rose, Jeffrey B Schwimmer, Claude Sirlin, Tanya Stein, Linda D Ferrell, Danuta Filipowski, Shannon Fleck, Camille Langlois, Philip Rosenthal, Melissa Young, Deana Rich, Karen Murray, Matthew Yeh, Sherry Boyett, Melissa J Contos, Michael Fuchs, Amy Jones, Velimir A C Luketic, Puneet Puri, Bimalijit Sandhu, Arun J Sanyal, Carol Sargeant, Kimberly Noble, Melanie White, Elizabeth M Brunt, David E Kleiner, Gilman D Grave, Edward C Doo, Jay H Hoofnagle, Patricia R Robuck, Averell Sherker, Patricia Belt, Jeanne M Clark, Michele Donithan, Milana Isaacson, Kevin P May, Laura Miriel, Alice Sternberg, James Tonascia, Aynur Ünalp-Arida, Mark Van Natta, Ivana Vaughn, Laura Wilson, Katherine Yates

Affiliations

¹ Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Indiana University School of Medicine, Indianapolis, IN. Electronic address: jpmolles@iu.edu.
² Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla, CA; Department of Gastroenterology, Rady Children's Hospital, San Diego, CA; Liver Imaging Group, Department of Radiology, University of California, San Diego School of Medicine, La Jolla, CA.
³ Data Coordinating Center, Johns Hopkins University, Baltimore, MD.
⁴ Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Seattle Children's Hospital, Seattle, WA.
⁵ Department of Pathology and Laboratory Medicine, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN.
⁶ Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Columbia University, New York, NY.
⁷ Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO.
⁸ Division of Pediatric Gastroenterology and Nutrition, Johns Hopkins Children's Center, Baltimore, MD.

PMID: 24360992
PMCID: PMC3962701
DOI: 10.1016/j.jpeds.2013.10.071

Histological abnormalities in children with nonalcoholic fatty liver disease and normal or mildly elevated alanine aminotransferase levels

Jean P Molleston et al. J Pediatr. 2014 Apr.

. 2014 Apr;164(4):707-713.e3.

doi: 10.1016/j.jpeds.2013.10.071. Epub 2013 Dec 19.

Authors

Collaborators

NASH Clinical Research Network:
Stephanie H Abrams, Leanel Angeli Fairly, Carol Hawkins, Margaret Stager, Parvathi Mohan, Stephanie DeVore, Rohit Kohli, Kathleen Lake, Stavra Xanthakos, Joel E Lavine, Ali Mencin, Nadia Ovchinsky, Elizabeth Byam, Oscar W Cummings, Ann Klipsch, Jean P Molleston, Girish Subbarao, Caroline Devadason, Kimberly Pfeifer, Ann Scheimann, Michael Torbenson, Nanda Kerkar, Frederick Suchy, Katherine Dunne, Mark H Fishbein, Katie Jacques, Ann Quinn, Cindy Riazi, Peter F Whitington, Sarah Barlow, Jose Derdoy, Debra King, Andrea Morris, Joan Siegner, Susan Stewart, Brent A Neuschwander-Tetri, Judy Thompson, Cynthia Behling, Jennifer Collins, Janis Durelle, Anya Morgan, Steven Rose, Jeffrey B Schwimmer, Claude Sirlin, Tanya Stein, Linda D Ferrell, Danuta Filipowski, Shannon Fleck, Camille Langlois, Philip Rosenthal, Melissa Young, Deana Rich, Karen Murray, Matthew Yeh, Sherry Boyett, Melissa J Contos, Michael Fuchs, Amy Jones, Velimir A C Luketic, Puneet Puri, Bimalijit Sandhu, Arun J Sanyal, Carol Sargeant, Kimberly Noble, Melanie White, Elizabeth M Brunt, David E Kleiner, Gilman D Grave, Edward C Doo, Jay H Hoofnagle, Patricia R Robuck, Averell Sherker, Patricia Belt, Jeanne M Clark, Michele Donithan, Milana Isaacson, Kevin P May, Laura Miriel, Alice Sternberg, James Tonascia, Aynur Ünalp-Arida, Mark Van Natta, Ivana Vaughn, Laura Wilson, Katherine Yates

Affiliations

¹ Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Indiana University School of Medicine, Indianapolis, IN. Electronic address: jpmolles@iu.edu.
² Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla, CA; Department of Gastroenterology, Rady Children's Hospital, San Diego, CA; Liver Imaging Group, Department of Radiology, University of California, San Diego School of Medicine, La Jolla, CA.
³ Data Coordinating Center, Johns Hopkins University, Baltimore, MD.
⁴ Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Seattle Children's Hospital, Seattle, WA.
⁵ Department of Pathology and Laboratory Medicine, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN.
⁶ Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Columbia University, New York, NY.
⁷ Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO.
⁸ Division of Pediatric Gastroenterology and Nutrition, Johns Hopkins Children's Center, Baltimore, MD.

PMID: 24360992
PMCID: PMC3962701
DOI: 10.1016/j.jpeds.2013.10.071

Abstract

Objective: To investigate the histological spectrum of nonalcoholic fatty liver disease (NAFLD) in children with normal, mildly elevated (26-50 U/L boys, 23-44 U/L girls), or elevated (>50 U/L in boys, >44 U/L in girls) serum alanine aminotransferase (ALT) levels.

Study design: The Nonalcoholic Steatohepatitis Clinical Research Network enrolls children aged 5-18 years with NAFLD. We analyzed baseline clinical and histological data from 91 children with suspected NAFLD and normal or mildly elevated ALT and liver biopsy analysis within 180 days of ALT measurement, and compared them with data from 392 children with elevated ALT.

Results: Seventeen of the 91 children with suspected NAFLD (19%) had a normal ALT level, and 74 (81%) had a mildly elevated ALT level. Overall, 45% of the biopsy specimens analyzed had steatosis ≥33%, 22% had grade ≥2 lobular inflammation, 81% had portal inflammation, 29% had ballooned hepatocytes, 35% had "suspicious/borderline" steatohepatitis, 8% had definite nonalcoholic steatohepatitis, 34% had an NAFLD activity score ≥4, and 46% had fibrosis (38% mild/moderate and 8% bridging/cirrhosis). Marked steatosis (50% vs 24%) and fibrosis (54% vs 12%) were significantly more common in the patients with mildly elevated ALT compared with those with normal ALT, with no difference in ballooning, inflammation, or NAFLD activity score ≥4 between the 2 groups. Fibrosis stage 3/4 was seen in none of the children with normal ALT, in 9% of those with mildly elevated ALT, and in 15% of those with elevated ALT.

Conclusion: Liver biopsy specimens from children with NAFLD with normal or mildly elevated ALT levels show significant histological abnormalities, including advanced fibrosis in children with mildly elevated ALT. Thus, measurement of ALT may underestimate liver injury in NAFLD. The use of appropriate ALT cutoff levels can help identify children at risk for more severe disease.

Trial registration: ClinicalTrials.gov NCT01061684.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

**Figure 1**
Percent of children in each NASH diagnosis category for normal, mildly elevated, and elevated ALT. NASH diagnosis categories are NAFLD/no NASH, Borderline Zone 3 (1a), Borderline Zone 1 (1b), Definite (2).

**Figure 2**
Percent of biopsies in fibrosis stages None, Mild, Moderate, and Advanced for each ALT group.

See this image and copyright information in PMC

Comment in

There's more under the nonalcoholic fatty liver disease umbrella than an elevated alanine aminotransferase level.
Kohli R. Kohli R. J Pediatr. 2014 Apr;164(4):684-6. doi: 10.1016/j.jpeds.2013.12.026. Epub 2014 Jan 23. J Pediatr. 2014. PMID: 24461787 No abstract available.

References

1. Alisi A, Manco M, Vania A, Nobili V. Pediatric Nonalcoholic Fatty Liver Disease in 2009. J Pediatr. 2009;155:469–474. - PubMed
1. Patton HM, Lavine JE, Van Natta ML, Schwimmer JB, Kleiner D, Molleston J. Clinical correlates of histopathology in pediatric nonalcoholic steatohepatitis. Gastroenterology. 2008;135:1961–1971. - PMC - PubMed
1. Lavine JE, Schwimmer JB. Nonalcoholic fatty liver disease in the pediatric population. Clin Liver Dis. 2004;8:549–558. - PubMed
1. Barlow SE. Expert committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: summary report. Pediatrics. 2007;120:S164–S192. - PubMed
1. Strauss RS, Barlow SE, Dietz WH. Prevelance of abnormal serum aminotransferase values in overweight and obese adolescents. J Pediatr. 2000;136:727–733. - PubMed

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Histological abnormalities in children with nonalcoholic fatty liver disease and normal or mildly elevated alanine aminotransferase levels

Collaborators

Affiliations

Histological abnormalities in children with nonalcoholic fatty liver disease and normal or mildly elevated alanine aminotransferase levels

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

Comment in

References

Publication types

MeSH terms

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Associated data

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LinkOut - more resources

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Medical