NASH severity assessed by the nafld activity score (NAS) does not add prognostic information to fibrosis stage in patients with nafld

Abstract

BACKGROUND: Previous studies have shown that the presence of non-alcoholic steatohepatitis (NASH) and fibrosis stage carry prognostic information in patients with NAFLD. Here we aimed to assess whether grading with the NAFLD activity score (NAS) had any additional prognostic value to fibrosis stage. METHODS: We conducted an individual participant data Meta Analysis of patients with NAFLD who had baseline biopsy. NASH is defined as NAFLD activity score >= 4 with score of at least 1 for steatosis, lobular inflammation, and ballooning. The primary outcome was a composite endpoint of all-cause mortality, decompensation of cirrhosis (ascites, variceal haemorrhage, hepatic encephalopathy), hepatocellular carcinoma, liver transplantation or progression to a model of end stage liver disease score >= 15. Studyspecific cumulative hazard functions and derived aggregated survival curves were built for F0-1, F2-3 and F4. Within each grouping we further divided cases into those without NASH, and those with NASH and NAS < 6 or NAS >= 6. Survival curves were compared using a study-stratified log-rank test. RESULTS: Data from 29 studies and 2,518 patients with biopsy proven NAFLD were included in the analysis (45% females, median age 54 (IQR 19) years, 46% with type II diabetes mellitus) 48% participants had NASH. The primary outcome was reached in 5.8% (n = 145) after a median follow-up of 58 months. In patients without cirrhosis, the presence and severity of NASH did not have any impact on developing the composite end point during follow-up of NASH (p = 0.43 for F0-1, Figure 1a; p = 0.95 for F2- 3, Figure 1b). In patients with cirrhosis the survival curves appeared to diverge, but the differences between NAS categories did not reach significance probably due to small numbers (p = 0.054, Figure 1c). CONCLUSIONS: The NAS score remains useful for the diagnosis of NASH but based on our data carries no prognostic information in non-cirrhotic NAFLD. In NAFLD cirrhosis, conclusions are limited by relatively small numbers.