Since the initial description of nonalcoholic steatohepatitis (NASH), several sets of pathologic criteria for its diagnosis have been proposed. However, their interprotocol agreement and ability to predict long-term liver-related mortality (LRM) have not been demonstrated. In this study, we examined patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) for whom liver biopsy slides and clinical and mortality data were available. Liver biopsy samples were evaluated for a number of pathologic features and were classified according to the presence or absence of NASH by (1) the original criteria for NAFLD subtypes, (2) the nonalcoholic fatty liver disease activity score (NAS), (3) the Brunt criteria, and (4) the current study's criteria. All NASH diagnostic criteria and individual pathologic features were tested for agreement and for their independent associations with LRM, which were determined with a Cox proportional hazards model. Two hundred fifty-seven NAFLD patients with complete data were included. The diagnoses of NASH by the original NAFLD subtypes and by the current study's definition of NASH were in almost perfect agreement (j 5 0.896). However, their agreement was moderate with NAS (j 5 0.470 and j 5 0.511, respectively) and only fair to moderate with the Brunt criteria (j 5 0.365 and j 5 0.441, respectively). Furthermore, the agreement of the Brunt criteria with NAS was relatively poor (j 5 0.178). During the follow-up (median 5 146 months), 31% of the patients died (9% were LRM). After we controlled for confounders, a diagnosis of NASH by the original criteria for NAFLD subtypes [adjusted hazard ratio 5 9.94 (95% confidence interval 5 1.28-77.08)] demonstrated the best independent association with LRM. Among the individual pathologic features, advanced fibrosis showed the best independent association with LRM [adjusted hazard ratio 5 5.68 (95% confidence interval 5 1.50-21.45)]. Conclusion: The original criteria for NAFLD subtypes and the current study's criteria for NASH were in almost perfect agreement, but their level of agreement with the NAS and Brunt criteria was lower. A diagnosis of NASH by the original criteria for NAFLD subtypes demonstrated the best predictability for LRM in NAFLD patients.

This long-term follow-up of NAFLD patients confirms that NASH patients have higher risk of liver-related mortality than non-NASH. Additionally, patients with NAFLD and type II diabetes are at highest risk for overall and liver-related mortality.

SUMMARY BackgroundPatient-reported outcomes like health-related quality of life (HRQL) have become increasingly important for full assessment of patients with chronic liver diseases (CLD).

SUMMARY BackgroundThe relative impact of non-alcoholic fatty liver disease (NAFLD) on health-related quality of life (HRQL) compared to other chronic liver diseases has not been fully explored.

This NAFLD Diagnostic Panel based on a clinical and laboratory data has good performance characteristics and is easy to use. This biomarker panel could become useful in the management of patients with NAFLD.