1Department of Pathology, University of California, San Francisco, San Francisco, California, USA.
2Department of Pathology, Cleveland Clinic, Cleveland, Ohio, USA.
3Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
4Sharp Memorial Hospital, San Diego, California, USA.
5Department of Pathology, Indiana University, Indianapolis, Indiana, USA.
6Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA.
7Department of Pathology, Saint Louis University, St. Louis, Missouri, USA.
8Department of Internal Medicine, Saint Louis University, St. Louis, Missouri, USA.
9Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
10Department of Pathology, University of Washington, Seattle, Washington, USA.
11Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland, USA.
Background and aims: The NAFLD activity score was developed to measure histologic changes in NAFLD during therapeutic trials. Hepatocyte ballooning (HB) is the most specific feature in steatohepatitis diagnosis, yet the impact of variations in HB has not been incorporated.
Approach and results: Liver biopsies from patients enrolled in the NASH Clinical Research Network with an initial diagnosis of NASH or NAFL (n=1688) were evaluated to distinguish classic hepatocyte ballooning (cHB) from smaller, nonclassic hepatocyte ballooning (nHB), and also to designate severe ballooning and assign an extended hepatocyte ballooning (eB) score [0 points, no ballooning (NB); 1 point, few or many nHB; 2 points, few cHB; 3 points, many cHB; 4 points, severe cHB] to the biopsy assessment. The eB score was reproducible among NASH CRN liver pathologists (weighted kappa 0.76) and was significantly associated with older age (mean 52.1 y, cHB; 48.5 y, nHB, p<0.001), gender (72.3% female, cHB; 54.5% female, nHB, p<0.001), diabetes (49.8% diabetes, cHB; 28.2% diabetes, nHB, p<0.001), metabolic syndrome (68.5% metabolic syndrome, nHB; 50.2% metabolic syndrome, NB, p<0.001), and body mass index [33.2, 34.2, 35 mean body mass index (kg/m2); NB, nHB, and cHB, respectively, p<0.05]. Finally, fibrosis stage, as a marker of disease severity, was significantly correlated with the eB score (p<0.001).
Conclusions: The eB score allows for a reproducible and more precise delineation of the range of ballooned hepatocyte morphology and corresponds with both clinical features of NASH and fibrosis stage.