Identifying Nonalcoholic Fatty Liver Disease Advanced Fibrosis in the Veterans Health Administration
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Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Severe NAFLD with advanced fibrosis results in substantial morbidity and mortality. Associated with metabolic syndrome, NAFLD is often initially clinically silent, yet intensive lifestyle intervention with 7% or greater weight loss can improve or resolve NAFLD. Using a Veterans Health Administration (VHA) liver biopsy cohort, we evaluated simple noninvasive fibrosis scoring systems to identify NAFLD with advanced fibrosis (or severe disease) to assist providers.
In our retrospective study of a national VHA sample of patients with biopsy-proven NAFLD or normal liver (2005–2015), we segregated patients by fibrosis stage (0–4). Non-NAFLD liver disease was excluded. We evaluated the diagnostic accuracy of the NAFLD fibrosis score (NFS), fibrosis-4 calculator (FIB-4), aspartate aminotransferase-to-alanine aminotransferase ratio (AST/ALT ratio), AST-to-platelet ratio index (APRI), and body mass index, AST/ALT ratio, and diabetes (BARD) score by age groups.
We included 329 patients with well-defined liver histology (296 NAFLD and 33 normal controls without fibrosis), in which 92 (28%) had advanced (stage 3–4) fibrosis. Across all age groups, NFS and FIB-4 best predicted advanced fibrosis (NFS with 0.676 threshold: AUROC 0.71–0.76, LR + 2.30–22.05, OR 6.00–39.58; FIB-4 with 2.67 threshold: AUROC of 0.62–0.80, LR + 4.70–27.45, OR 16.34–59.65).
While NFS and FIB-4 scores exhibit good diagnostic accuracy, FIB-4 is optimal in identifying NAFLD advanced fibrosis in the VHA. Easily implemented as a point-of-care clinical test, FIB-4 can be useful in directing patients that are most likely to have advanced fibrosis to GI/hepatology consultation and follow-up.
KeywordsFatty liver Nonalcoholic steatohepatitis Fibrosis Fibrosis prediction score
Area under the ROC
AST-to-platelet ratio index
- BARD score
Body mass index, AST/ALT ratio, and diabetes
Alcohol Use Disorders Identification Test Alcohol Consumption Questions
Body mass index
Nonalcoholic fatty liver
Nonalcoholic fatty liver disease
NAFLD fibrosis score
Receiver operating characteristic curve
Veterans Health Administration
All authors had access to the data and a role in writing/preparing the manuscript.
This work was supported in part by resources from the Veterans Affairs (VA) Cooperative Studies Program Epidemiology Center, Durham, and the VA Ann Arbor Healthcare Systems.
Compliance with ethical standards
Conflict of interest
The views expressed in this paper are those of the authors and do not necessarily represent the policies or position of, nor imply endorsement from, the Department of Veterans Affairs, or US Government. Christine M. Hunt has received consultancy fees from Otsuka and Indivior.
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