Original article—liver, pancreas, and biliary tract
Comparison of Noninvasive Markers of Fibrosis in Patients With Nonalcoholic Fatty Liver Disease

https://doi.org/10.1016/j.cgh.2009.05.033Get rights and content

Background & Aims

There is a need for a reliable and inexpensive noninvasive marker of hepatic fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). We compared the performance of the FIB4 index (based on age, aspartate aminotransferase [AST] and alanine aminotransferase [ALT] levels, and platelet counts) with 6 other non-invasive markers of fibrosis in patients with NAFLD.

Methods

Using a nation-wide database of 541 adults with NAFLD, jackknife-validated areas under receiver operating characteristic curves (AUROC) of FIB4 and 7 other markers were compared. The sensitivity at 90% specificity, 80% positive predictive value, and 90% negative predictive values were determined along with cutoffs for advanced fibrosis.

Results

The median FIB4 score was 1.11 (interquartile range = 0.74–1.67). The jackknife-validated AUROC for FIB4 was 0.802 (95% confidence interval [CI], 0.758–0.847), which was higher than that of the NAFLD fibrosis score (0.768; 95% CI, 0.720–0.816; P = .09), Goteburg University Cirrhosis Index (0.743; 95% CI, 0.695–0.791; P < .01), AST:ALT ratio (0.742; 95% CI, 0.690–0.794; P < .015), AST:platelet ratio index (0.730; 95% CI, 0.681–0.779; P < .001), AST:platelet ratio (0.720; 95% CI, 0.669–0.770; P < .001), body mass index, AST:ALT, diabetes (BARD) score (0.70; P < .001), or cirrhosis discriminant score (0.666; 95% CI, 0.614–0.718; P < .001). For a fixed specificity of 90% (FIB4 = 1.93), the sensitivity in identifying advanced fibrosis was only 50% (95% CI, 46–55). A FIB4 ≥ 2.67 had an 80% positive predictive value and a FIB4 index ≤ 1.30 had a 90% negative predictive value.

Conclusions

The FIB4 index is superior to 7 other noninvasive markers of fibrosis in patients with NAFLD; however its performance characteristics highlight the need for even better noninvasive markers.

Section snippets

Study Population

The study population consisted of subjects with histologically proven NAFLD who were enrolled in the National Institutes of Health (NIH) NASH Clinical Research Network (CRN). The NASH CRN has three sets of subjects: (1) those enrolled in a natural history database; (2) those enrolled in a randomized clinical trial of pioglitazone or vitamin E versus placebo (PIVENS) in adults; and (3) a randomized clinical trial of metformin or vitamin E versus placebo (TONIC) in pediatric subjects with NAFLD.

Results

A total of 541 subjects were included for this analysis. Of these, 325 (60%) were women and 400 (74%) were Caucasian (Table 2); 105 (19%) had type 2 diabetes mellitus and 239 (44%) were hypertensive. A total of 317 subjects had steatohepatitis; of these, 101 subjects had advanced fibrosis. A total of 224 subjects who had fatty liver disease but did not meet the NASH CRN definition of steatohepatitis were also included. Of these 224 subjects, 24 had advanced fibrosis. As expected, subjects with

Discussion

An ideal noninvasive test for assessment of hepatic fibrosis would be one that is sensitive, specific, free of additional cost to the patient, and applicable across all chronic liver diseases. In the context of NAFLD, such a test should also be able to distinguish between a fatty liver and steatohepatitis. Unfortunately, none of the currently available tests meets these criteria and the search for such a marker goes on.

In the absence of an ideal marker, the utility of any marker should take

Acknowledgments

Members of the Nonalcoholic Steatohepatitis Clinical Research Network: Clinical Centers: Baylor College of Medicine, Houston, TX: Stephanie Abrams, MD, Diana Arceo, Denise Espinosa, and Leanel Fairly. Case Western Reserve University Clinical Centers: MetroHealth Medical Center, Cleveland, OH: Arthur McCullough, MD, PI, Diane Bringman, RN, BSN, Srinivasan Dasarathy, MD, Carol Hawkins, RN, Yao-Chang Liu, MD, Nicholette Rogers, PhD, PA-C, and Margaret Stager, MD; and Cleveland Clinic Foundation,

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    Conflicts of interest The authors disclose no conflicts.

    Funding This work was supported by grants from the National Institutes of Health to the NASH Clinical Research Network (U01DK61718, U01DK61728, U01DK61731, U01DK61732, U01DK61734, U01DK61737, U01DK61738, U01DK61730, U01DK61713).

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