Low clinical relevance of the nonalcoholic fatty liver disease activity score (NAS) in predicting fibrosis progression

Background/Aims. The nonalcoholic fatty liver disease (NAFLD) activity score (NAS) is a newly proposed system to grade the necroinflammatory activity in liver biopsies of NAFLD patients. This study evaluates the usefulness of the NAS in predicting clinical deterioration and fibrosis progression in NAFLD. Methods. One hundred and twenty-nine patients with biopsy-proven NAFLD were included in a long-term histological follow-up study. Clinical course and change in fibrosis stage were compared between nonalcoholic steatohepatitis (NASH), "borderline NASH," and "not NASH" patients. Significant fibrosis progression was defined as progression of more than one fibrosis stage or development of end-stage liver disease during follow-up. Results. Eighty-eight patients accepted reevaluation and 68 underwent repeat liver biopsy. Mean time between biopsies was 13.8 +/- 1.2 years (range 10.3-16.3). At baseline, NASH was diagnosed in 2 (1.6%) patients, and at follow-up, in 1 (1.5%) patient. A trend toward higher baseline NAS was seen in patients (n = 7) who developed end-stage liver disease (3.1 +/- 0.9 vs. 2.2 +/- 1.0; p = 0.050). Baseline NAS was associated with progressive disease in a univariate binary logistic regression analysis (p = 0.024), but no difference was seen in the multivariate analysis including the NAS, portal inflammation, and perisinusoidal fibrosis. Moreover, 18% of patients without NASH progressed significantly in fibrosis stage. Conclusions. The ability of the NAS to predict progression of NAFLD is poor. The clinical usefulness of the score is limited due to the significant overlap in clinical development between NAS score groups. To use the NAS as endpoint in treatment trial is not justified.