In fact, with the recommended NAS threshold of 5, only 61% of NAFLD cases who died of liver-related causes were diagnosed as having NASH. On the other hand, the Brunt criteria demonstrated the lowest specificity of the four pathologic protocols. In fact, our data indicated that 85% of individuals with NAFLD who did not die from liver-related causes were still diagnosed with NASH by the Brunt criteria, whereas other protocols diagnosed 33% to 60% of those with NASH. However, when patients with Brunt’s

grade 1 NASH were excluded from the NASH group, the proportion of patients with NASH diagnoses among those who did not die from liver-related causes decreased to 41%, and the proportion of correctly included NASH diagnoses (those resulting in LRM) remained at the level of 89%. These data again suggest that Brunt grade 1 for NASH leads to an overdiagnosis of NAFLD BMN 673 ic50 in patients who do not develop progressive liver disease causing liver-related deaths. In an attempt to assess the predictability of NASH diagnoses made by the four separate pathologic protocols, we ran a multivariate analysis. After we controlled for important confounders (age, gender, ethnicity, and presence of obesity and diabetes), a diagnosis of NASH made by the original criteria

for NAFLD subtypes [aHR = 9.94 (95% CI = 1.28-77.08)] and a diagnosis of NASH made by the current study’s criteria for subtypes [aHR = 4.43 (95% CI = 0.97-20.20)] were independent predictors of LRM (Table 4). Again, similarly to the interprotocol agreement analysis, check details we attempted to find the optimal NAS value for predicting LRM. In our analysis, for an association with LRM, the best NAS threshold was 4 (i.e., a patient with NAS ≥ 4 was presumed to have NASH). Nevertheless, the association of this NAS threshold with LRM remained nonsignificant [log-rank P = 0.098, aHR = 2.92 (95% CI = 0.95-8.95)].

Additionally, other thresholds for NAS (both higher and lower) did not return any significant association with LRM. Next, we assessed individual Adenosine triphosphate pathologic features used in the original criteria for NAFLD subtypes for their ability to predict LRM. In a Cox proportional hazards model consisting of all the originally independent pathologic features (i.e., bridging fibrosis and cirrhosis were not included because they could be described as linear combinations of other features) and using each feature as an ordinal parameter, only fibrosis independently predicted LRM. After each pathologic feature was transformed into binary parameters, univariate survival analyses showed that portal inflammation [grade ≥ 2; HR = 6.68 (95% CI = 2.20-20.3), P = 0.0008], ballooning degeneration [grade ≥ 2; HR = 5.32 (95% CI = 1.89-14.9), P = 0.