21 (95% CI = 1.66-10.7),

P = 0.0024], portal fibrosis [grade > 2; HR = 14.1 (95% CI = 5.47-36.5), P < .0001], and pericellular fibrosis [grade > 2; HR = 4.86 (95% CI = 1.73-13.7), P = 0.0027] on the liver biopsy samples were all associated with LRM. Additionally, histologic documentation of advanced fibrosis grade ≥ 2 [HR = 20.4 (95% CI = 5.9-70.5), P < 0.0001] or any cirrhosis [HR = 10.6 (95% CI = 4.19-26.7), P < 0.0001] was also associated with LRM. In these univariate analyses, the grades of steatosis and lobular inflammation were not associated with LRM. buy Sunitinib Using multivariate analyses, we further tested these pathologic features as independent predictors of LRM. As a result, using these binary parameters in the Cox proportional hazards model, we found that portal fibrosis graded as ≥3 (with the current study’s fibrosis grading, this included all patients with bridging fibrosis and cirrhosis) remained independently associated with LRM [aHR = 5.68 (95% CI = 1.50-21.45)]. Similarly, when we tested pathologic features graded with NAS, advanced fibrosis (stage 4) was independently associated with LRM [aHR = 5.62 (95% CI = 1.92-6.46)]. The LRM survival curves for individuals with different grades of fibrosis graded according ABT-263 to the current study’s criteria (Fig. 1A) and the NAS criteria (Fig. 1B) are shown. This is the first study providing the interprotocol agreement and predictability

values for LRM of four sets of pathologic criteria for diagnosing NASH. This study used a well-defined cohort of NAFLD patients for whom clinical data, liver biopsy slides, and long-term mortality data were available. We have confirmed the findings of previous studies2, 6-18 reporting that, regardless of the specific pathologic criteria for

NASH, patients with a histologic diagnosis of NASH have higher LRM. Our study is the first study to assess interprotocol agreement between different pathologic criteria for NASH. Our data show that diagnoses of NASH by the original criteria for NAFLD subtypes15 and diagnoses of NASH by the current study’s NASH criteria18 were in almost perfect agreement. On the other hand, diagnoses of NASH made by NAS threshold of17 showed only moderate agreement with diagnoses of NASH made by the other pathologic criteria for NASH. Nevertheless, NAS threshold of 5 returned an almost 100% positive predictive value for NASH as a cause OSBPL9 of liver-related death. However, this NAS threshold, missed every third NAFLD patient who would ultimately die of liver-related causes, whereas the other NASH pathologic criteria used in this study successfully predicted 90% to 100% of cases dying from liver-related causes. These findings are consistent with the conclusions of a recent article by the authors of NAS that discusses the role of NAS thresholds.21 In fact, our data indicate that a NAS value ≥5 seems to be a strict criterion that could potentially lead to underdiagnosis of NAFLD in patients who will ultimately die of liver-related causes.