Simple non-invasive biomarkers of advanced fibrosis in the evaluation of non-alcoholic fatty liver disease

Background and aims. Non-alcoholic fatty liver disease (NAFLD) is a common, morbid disease with profound implications for the overall health of the patient. We set out to determine the clinical predictors of advanced histology in the referral population. Methods. We performed a retrospective review of all biopsy-proven NAFLD patients, including 358 unique patients first seen between 1996 and 2009. Liver histology and ultrasound images were reviewed prospectively by clinicians who were blinded to clinical information and test indication. Results. Compared with men, women tended to present at an older age (51.4 +/- 10.6 vs 45.3 +/- 11.2 years, P< 0.001), were more likely to be Caucasian (P=0.003), less likely to present with an elevated alanine aminotransferase (ALT) (75.2% vs 88.8%), and more likely to have advanced non-alcoholic steatohepatitis (NASH) (44.7% vs 29.9%; P=0.04) and advanced fibrosis (23.3% vs 14.1%; P=0.03). In multivariate logistic regression, body mass index (BMI) +/- 30 kg/m 2 (odds ratio (OR) 2.21; 95% confidential interval (CI): 1.23-4.08), female gender (OR 1.76; 95% CI: 1.01-3.10) and aspartate aminotransferase (AST) > 40 IU/L (OR 2.00; 95% CI: 1.14-3.55) were associated with a NAFLD activity score > 4. The sensitivity and specificity of an AST to platelet ratio index (APRI) > 1 for significant fibrosis was 30.0% (95% CI: 17.2-45.4%) and 92.8% (95% CI: 88.295.8%), respectively; the likelihood ratio is 4.2. In multivariate logistic regression, APRI > 1 was the most significant predictor of advanced fibrosis (OR 3.85; 95% CI: 1.55-9.59). In patients without ultrasound-detected steatosis, 20% had advanced fibrosis and 16.7% had active NASH. Conclusion. Patients with suspected NAFLD should routinely be evaluated for advanced liver disease, including non-invasive indices of fibrosis such as APRI, and serious consideration given to liver biopsy.