Kleiner DE, Brunt EM, Van Natta M, et al. Nonalcoholic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease

Johns Hopkins University, Baltimore, Maryland, United States
Hepatology (Impact Factor: 11.06). 06/2005; 41(6):1313-21. DOI: 10.1002/hep.20701
Source: PubMed


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 > or =5 correlated with a diagnosis of NASH, and biopsies with scores of less than 3 were diagnosed as "not NASH."

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    • "In addition, to avoid confusing the results related to potential liver iron deposition, an evaluation of liver iron concentration was performed and the fat fraction was validated only if liver iron concentration was less than 36 mmol/g. Although this formula may be ambiguous for high values of fat deposition because it has a theoretical signal intensity peak at 50%, and the signal may decrease above, this is not a clinical problem as this would only correspond to situations of extreme severity, which are higher than histologic grade 3 as described by Kleiner et al. (2005) and were not encountered in this study. The histologic grade and the measured fat fraction, even if expressed as percentages, are dissimilar. "
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    • "The slides were examined three times at 400× magnification under a light microscope (Leica DM LB, Leica Microsystems, Heerbrugg, Switzerland) in a randomized manner using the criteria of Kleiner et al. (2005). "
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