Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings

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 (NA) 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 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 a NAS ≥ 5, while 28% of borderline SH and 7% of "not SH" biopsies had NAS ≥ 5. Of biopsies with a 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 ALT and AST, while the diagnosis of SH was associated with features of the metabolic syndrome. Conclusions 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.

Metabolomic‐based noninvasive serum test to diagnose nonalcoholic steatohepatitis: Results from discovery and validation cohorts

“…After validation, the test maintained a suitable capacity to distinguish NASH from NAFL (AUROC of 0.79 ± 0.04) with a good specificity of 0.81, indicating that it may perform well for NASH diagnosis because of low false‐positive errors 45. This test divided patients classified as NASH borderline between the two diagnostic categories (NAFL and NASH), which agrees with previous studies 21, 22. Analysis of the impact of the stage of each of the histologic features of the NAS system on the accuracy of the diagnostic test revealed that, in general, the error rate of NASH diagnosis ranged between 20% and 40% for the different values of the features of the NAS system and between 30% and 60% for the different score values of fibrosis.…”

“…Histologic slides were processed as usual, employing hematoxylin and eosin and Masson's trichrome stains. For the discovery group, the histologic diagnosis of NAFLD was established by a single liver pathologist in each participating hospital, according to the criteria defined by Kleiner et al21 and Brunt et al22 Following assessment, patients were classified by the pathologists into the following three histologic groups: (1) NL, (2) NAFL (hepatic steatosis alone), and (3) NASH (presence as determined by the pathologist). None of the patients had cirrhosis.…”

Metastasis‐associated lung adenocarcinoma transcript 1 as a common molecular driver in the pathogenesis of nonalcoholic steatohepatitis and chronic immune‐mediated liver damage

“…(B) Liver MALAT1 expression levels are significantly associated with the full spectrum of NAFLD histologic severity. The severity of histologic features was graded according to scores described by Brunt et al12 and Kleiner et al11 as indicated in the Methods section. Horizontal lines refer to mean value.…”

“…Degree of steatosis was assessed according to the system developed by Kleiner et al11 based on the percentage of hepatocytes containing macrovesicular fat droplets. NASH and NAFLD activity score were defined as reported11, 12; NASH was defined as steatosis plus mixed inflammatory cell infiltration, hepatocyte ballooning and necrosis, Mallory's hyaline, and any stage of fibrosis, including absent fibrosis 11, 12. In patients with chronic HCV, liver histopathology was scored according to Ishak's fibrosis grading and staging system 13…”

Treating fatty liver disease by modulating mitochondrial pyruvate metabolism

“…It is also clear that in some patients NAFLD progresses to nonalcoholic steatohepatitis (NASH), which increases the risk of cirrhosis, liver failure, and hepatocellular carcinoma. At the current time, NASH is diagnosed based on liver biopsies showing characteristic histologic changes, including fat deposition, inflammation, hepatocyte ballooning, and importantly in terms of prognosis, fibrotic scarring 11, 12. While there are many treatments in development that specifically address individual aspects of liver disease, epidemiologic studies have defined a strong linkage between overnutrition and incidence of NAFLD, and this linkage is driving the prevalence of this disease of the liver to pandemic proportions 13.…”