Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score and ... : Hepatology (original) (raw)

Steatohepatitis/Metabolic Liver Disease

Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score and the Histopathologic Diagnosis in NAFLD: Distinct Clinicopathologic Meanings§Δ

Brunt, Elizabeth M.1*; Kleiner, David E.2; Wilson, Laura A.3; Belt, Patricia3; Neuschwander-Tetri, Brent A.4 for the NASH Clinical Research Network (CRN)

1 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO

2 Department of Laboratory Medicine, National Cancer Institute, Washington, DC

3 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD

4 Department of Medicine, Division of Gastroenterology and Hepatology, Saint Louis University, St. Louis, MO

*Address reprint requests to: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8118, St. Louis, MO 63110

Email:[email protected]

Received 5 October 2010; Accepted 6 December 2010

σ_Potential conflict of interest: Nothing to report._

Δ_The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (grants U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, U01DK061713), and the National Institute of Child Health and Human Development (NICHD). Several clinical centers use support from General Clinical Research Centers or Clinical and Translational Science Awards in conduct of NASH CRN Studies (grants UL1RR024989, M01RR000750, M01RR00188, UL1RR02413101, M01RR000827, UL1RR02501401, M01RR000065, M01RR020359, UL1RR025741)._

Abstract

The diagnosis of nonalcoholic steatohepatitis (NASH) is defined by the presence and pattern of specific histological abnormalities on liver biopsy. A separate system of scoring the features of nonalcoholic fatty liver disease (NAFLD) called the NAFLD Activity Score (NAS) was developed as a tool to measure changes in NAFLD during therapeutic trials. However, some studies have used threshold values of the NAS, specifically NAS ≥5, as a surrogate for the histologic diagnosis of NASH. To evaluate whether this unintended use of the NAS is valid, biopsy and clinical data from the 976 adults in NASH Clinical Research Network (CRN) studies were reviewed. Biopsies were evaluated centrally by the NASH CRN Pathology Committee. Definite steatohepatitis (SH) was diagnosed in 58.1%, borderline SH in 19.5% and “not SH” in 22%. The NAS was ≥5 in 50% and ≤4 in 49%; in this cohort only 75% of biopsies with definite SH had an NAS ≥5, whereas 28% of borderline SH and 7% of “not SH” biopsies had NAS ≥5. Of biopsies with an NAS ≥5, 86% had SH and 3% “not SH”. NAS ≤4 did not indicate benign histology; 29% had SH and only 42% had “not SH.” Higher values of the NAS were associated with higher levels of alanine aminotransferase and aspartate aminotransferase, whereas the diagnosis of SH was associated with features of the metabolic syndrome. Conclusion: The diagnosis of definite SH or the absence of SH based on evaluation of patterns as well as individual lesions on liver biopsies does not always correlate with threshold values of the semiquantitative NAS. Clinical trials and observational studies should take these different performance characteristics into account. (Hepatology 2011)