Liver Failure and Liver Disease
Design and validation of a histological scoring system for nonalcoholic fatty liver disease†
Article first published online: 24 MAY 2005
Copyright © 2005 American Association for the Study of Liver Diseases
Volume 41, Issue 6, pages 1313–1321, June 2005
How to Cite
Kleiner, D. E., Brunt, E. M., Van Natta, M., Behling, C., Contos, M. J., Cummings, O. W., Ferrell, L. D., Liu, Y.-C., Torbenson, M. S., Unalp-Arida, A., Yeh, M., McCullough, A. J. and Sanyal, A. J. (2005), Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology, 41: 1313–1321. doi: 10.1002/hep.20701
Potential conflict of interest: Nothing to report.
A list of members of the Nonalcoholic Steatohepatitis Clinical Research Network is located in the Appendix.
- Issue published online: 24 MAY 2005
- Article first published online: 24 MAY 2005
- Manuscript Accepted: 25 FEB 2005
- Manuscript Received: 12 NOV 2004
- National Institute of Diabetes & Digestive & Kidney Diseases. Grant Numbers: 1U01DK061718, 1U01DK061728, 1U01DK061731, 1U01DK061732, 1U01DK061734, 1U01DK061737, 1U01DK061738, 5U01DK061730, 7U01DK061713, N01HR761019
- National Institute of Child Health and Human Development
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.” (HEPATOLOGY 2005;41:1313–1321.)