Nonalcoholic fatty liver disease activity score and Brunt's pathologic criteria for the diagnosis of nonalcoholic steatohepatitis: What do they mean and do they agree?
Authors: Stefano Ballestri, Amedeo Lonardo, Paola Loria
Journal: Hepatology (2011)

We read with great interest two articles recently published in HEPATOLOGY that compare different histological classifications for nonalcoholic fatty liver disease (NAFLD).1, 2 The first study1 confirms the lack of a strict relationship between Brunt's classification3 and Kleiner's classification4 in a large cohort of American adults [κ statistic = 0.57, 95% confidence interval (CI) = 0.51-0.62]. The authors report that not all biopsy samples with a nonalcoholic fatty liver disease activity score (NAS) ≥ 5 met the diagnostic criteria for definite steatohepatitis (SH), and some cases with NAS ≤ 4 did; this indicates that an NAS threshold value of ≥5 cannot be used to reliably establish the presence or absence of SH. The second study2 reports an even lower level of agreement between Brunt's and Kleiner's classifications (κ statistic = 0.178; 95% CI = 0.117-0.240) and concludes that the diagnosis of SH by NAS, regardless of its threshold, is inappropriate. Moreover, fibrosis remained an independent predictor of liver-related mortality in a series of 257 NAFLD patients after a median follow-up of 146 months. Knowing that fibrosis obviously dictates survival for patients with NAFLD2 and that inflammation is the precursor lesion of fibrosis,5 we thought that it would be interesting to assess whether the findings published in the aforementioned studies1, 2 could be reproduced in a cohort of European patients with NAFLD who were evaluated at a single tertiary liver center. To this end, we compared the diagnostic yields of the two most widely followed histological classifications for our cohort of 96 NAFLD patients without cirrhosis. Histological liver samples were evaluated by a single experienced liver pathologist (L.L.); only biopsy samples at least 15 mm long with at least six portal tracts were considered eligible for analysis. According to Brunt's criteria, 31 patients did not have SH, and 65 patients did have SH; according to Kleiner's criteria, 61 patients did not have SH (i.e., NAS ≤ 4), and 35 did have SH (i.e., NAS ≥ 5). NAS was ≥5 in 53.8% and ≤4 in 46.2% of the patients with SH according to Brunt's criteria, whereas NAS was ≤4 in 100% of those without SH. All biopsy samples with NAS ≥ 5 fulfilled Brunt's diagnostic criteria for SH. NAS ≤ 4 did not indicate benign histological findings; this agreed with Brunt's most recent study1 because 49.8% of the patients with NAS ≤ 4 had SH according to Brunt's original criteria.3 Table 1 shows the independent predictors of SH according to a stepwise multivariate logistic regression analysis. On the basis of our experience and the findings of recent studies,1, 2 we can conclude that both classifications faithfully mirror metabolic derangements typical of SH. Moreover, the correlation between Brunt's and Kleiner's original classifications3, 4 is fair to moderate [κ statistic = 0.43, 95% CI = 0.27-0.59 (this study)]. This agreement, however, might be increased up to 0.74 (0.55-0.93) if the SH cutoff were lowered to NAS = 4 or up to 0.66 (0.47-0.85) if patients with a Brunt grade of 1 were no longer considered to have SH. Finally, we maintain that, by reflecting both inflammation and fibrosis more analytically, Brunt's original classification1 provides more substantial information to the practicing clinical hepatologist. Stefano Ballestri M.D.*, Amedeo Lonardo M.D.*, Paola Loria M.D.*, * Unit of Internal Medicine, Department of Internal Medicine, Endocrinology, Metabolism, and Geriatrics, University of Modena and Reggio Emilia, Modena, Italy.