Design and validation of a histological scoring system for nonalcoholic fatty liver disease

David E. Kleiner, Elizabeth M. Brunt, Mark Van Natta, Cynthia Behling, Melissa J. Contos, Oscar Cummings, Linda D. Ferrell, Yao Chang Liu, Michael S. Torbenson, Aynur Unalp-Arida, Matthew Yeh, Arthur J. McCullough, Arun J. Sanyal

Research output: Contribution to journalArticle

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Abstract

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in the absence of a history of significant alcohol use or other known liver disease. Nonalcoholic steatohepatitis (NASH) is the progressive form of NAFLD. The Pathology Committee of the NASH Clinical Research Network designed and validated a histological feature scoring system that addresses the full spectrum of lesions of NAFLD and proposed a NAFLD activity score (NAS) for use in clinical trials. The scoring system comprised 14 histological features, 4 of which were evaluated semi-quantitatively: steatosis (0-3), lobular inflammation (0-2), hepatocellular ballooning (0-2), and fibrosis (0-4). Another nine features were recorded as present or absent. An anonymized study set of 50 cases (32 from adult hepatology services, 18 from pediatric hepatology services) was assembled, coded, and circulated. For the validation study, agreement on scoring and a diagnostic categorization ("NASH," "borderline," or "not NASH") were evaluated by using weighted kappa statistics. Inter-rater agreement on adult cases was: 0.84 for fibrosis, 0.79 for steatosis, 0.56 for injury, and 0.45 for lobular inflammation. Agreement on diagnostic category was 0.61. Using multiple logistic regression, five features were independently associated with the diagnosis of NASH in adult biopsies: steatosis (P = .009), hepatocellular ballooning (P = .0001), lobular inflammation (P = .0001), fibrosis (P = .0001), and the absence of lipogranulomas (P = .001). The proposed NAS is the unweighted sum of steatosis, lobular inflammation, and hepatocellular ballooning scores. In conclusion, we present a strong scoring system and NAS for NAFLD and NASH with reasonable inter-rater reproducibility that should be useful for studies of both adults and children with any degree of NAFLD. NAS of ≥5 correlated with a diagnosis of NASH, and biopsies with scores of less than 3 were diagnosed as "not NASH."

Original languageEnglish
Pages (from-to)1313-1321
Number of pages9
JournalHepatology
Volume41
Issue number6
DOIs
StatePublished - Jun 2005

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Inflammation
Non-alcoholic Fatty Liver Disease
Fibrosis
Gastroenterology
Biopsy
Validation Studies
Liver Diseases
Logistic Models
Alcohols
Clinical Trials
Pediatrics
Pathology
Liver
Wounds and Injuries
Research

ASJC Scopus subject areas

  • Hepatology

Cite this

Kleiner, D. E., Brunt, E. M., Van Natta, M., Behling, C., Contos, M. J., Cummings, O., ... Sanyal, A. J. (2005). Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology, 41(6), 1313-1321. https://doi.org/10.1002/hep.20701

Design and validation of a histological scoring system for nonalcoholic fatty liver disease. / Kleiner, David E.; Brunt, Elizabeth M.; Van Natta, Mark; Behling, Cynthia; Contos, Melissa J.; Cummings, Oscar; Ferrell, Linda D.; Liu, Yao Chang; Torbenson, Michael S.; Unalp-Arida, Aynur; Yeh, Matthew; McCullough, Arthur J.; Sanyal, Arun J.

In: Hepatology, Vol. 41, No. 6, 06.2005, p. 1313-1321.

Research output: Contribution to journalArticle

Kleiner, DE, Brunt, EM, Van Natta, M, Behling, C, Contos, MJ, Cummings, O, Ferrell, LD, Liu, YC, Torbenson, MS, Unalp-Arida, A, Yeh, M, McCullough, AJ & Sanyal, AJ 2005, 'Design and validation of a histological scoring system for nonalcoholic fatty liver disease', Hepatology, vol. 41, no. 6, pp. 1313-1321. https://doi.org/10.1002/hep.20701
Kleiner, David E. ; Brunt, Elizabeth M. ; Van Natta, Mark ; Behling, Cynthia ; Contos, Melissa J. ; Cummings, Oscar ; Ferrell, Linda D. ; Liu, Yao Chang ; Torbenson, Michael S. ; Unalp-Arida, Aynur ; Yeh, Matthew ; McCullough, Arthur J. ; Sanyal, Arun J. / Design and validation of a histological scoring system for nonalcoholic fatty liver disease. In: Hepatology. 2005 ; Vol. 41, No. 6. pp. 1313-1321.
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AU - Cummings, Oscar

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