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."