Nonalcoholic fatty liver disease: assessment of variability in pathologic interpretations

The exact cause, prevalence, and rate of progression of nonalcoholic fatty liver disease (NAFLD) are unclear because of a lack of agreement on the pathologic features associated with the different types of NAFLD, their clinical syndromes, and because of a lack of accuracy in the interpretation of these pathologic features. Studies of NAFLD would be aided by a consistent and standardized approach to the interpretation of pathologic features. The aim of our study was to assess interobserver and intraobserver variation in the histologic abnormalities associated with NAFLD. We identified histologic features of NAFLD as reported in the literature, and we identified patients with the diagnosis of NAFLD through the databases of two large institutions. Histologic parameters were evaluated for each liver biopsy specimen by four hepatopathologists and twice by two of the four pathologists (blindly). Interobserver and intraobserver concordance among the pathologists was measured by kappa statistics. Nineteen histologic parameters compartmentalized into steatosis, inflammation, liver cell injury, and fibrosis were evaluated on 53 liver biopsy specimens. Significant, substantial, or moderate concordance was present in only six items: the extent of steatosis, sinusoidal location of fibrosis, perivenular fibrosis, grade of fibrosis, ballooning degeneration, and the presence of vacuolated nuclei. Substantial or moderate concordance also was seen for interobserver readings for location of steatosis and periportal injury. Parameters of inflammation were not scored as reliably as parameters of fibrosis and cell injury. We conclude that only some histologic features previously reported in NAFLD (especially those with substantial and moderate concordance for both interobserver and intraobserver interpretation) are interpreted uniformly by experienced pathologists. These histologic features might prove useful for the development of a standardized and reliable pathologic scoring system that includes the full histologic spectrum of NAFLD and its various clinical outcomes.