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Abstract

described. 6 Using published cutoffs of 0.35 to rule out, and 0.67 to rule in, our main outcome was to validate these FAST score cutoffs in identifying NASH þ NAS 4 þ F2 in a cohort of US Veterans. Measures of diagnostic accuracy (ie, sensitivity, specificity, negative and positive predictive values [NPV and PPV], area under the receiver operating curve [C-statistic], and Youden index J) were assessed. The study was approved by the institutional review board. A 199 US Veterans (91% male), median (interquartile range) age of 61 (52-67) years, and body mass index of 32.8 (28.5-36.7) kg/m 2 were studied. We observed NASH in 57 (29%), NAS 4 in 68 (34%), and fibrosis stage 2 in 93 (47%). Combined NASH þ NAS 4 þ F2 was present in 28 (14.1%). The FAST score had a C-statistic of 0.75 (95% confidence interval, 0.69-0.81) and Youden index J of 0.44 (95% confidence interval, 0.31-0.54). The FAST score cutoff 0.35 to rule out 4 had a sensitivity and NPV of 1.00, and 0.67 to rule in 4 had a specificity of 0.69 with a PPV of 0.26 for NASH þ NAS 4 þ F2 (comparison with the published data in Table 1). The median FAST scores were similar for different quartiles of interval period from biopsy. For a fixed sensitivity of 0.90 in our cohort to rule out, the FAST score cutoff was 0.49, with a PPV of 0.24 and an NPV of 0.96. Similarly, for specificity of 0.90 to rule in, the FAST score cutoff was 0.85, with a PPV of 0.31 and an NPV of 0.87. To our knowledge, this is the first study to validate FAST score in stratifying high-risk NASH among the US Veterans. Our results are consistent with those published recently 4 despite an older, male-predominant population in a real-world clinical practice. Our sample size, when compared with the validation cohorts, 4 is the second largest study group. Although FAST score of 0.35 accurately excludes high-risk NASH, the rule in cutoff 0.67 had higher false negatives in our cohort for diagnosing high-risk NASH. Using newly generated cutoffs 0.49 to rule out and 0.85 to rule in, we identified 96% and 87% Veterans, respectively, who did not have high-risk NASH. It is possible that low PPV is likely caused by relatively low prevalence of NASH þ NAS 4 þ F2 in our cohort. In conclusion, the newly derived FAST score cutoffs are reliable noninvasive tests to classify subjects with low-and high-risk NASH. We propose to implement these cutoffs and anticipate to reduce the need for liver biopsies by 44% while maintaining a minimal falsepositive rate of 1.5% in evaluating US Veterans with NASH.

Baseline Tyrosine Level Is Associated with Dynamic Changes in FAST Score in NAFLD Patients under Lifestyle Modification

“…However, an independent external validation study by Puri et al involving 199 United States veterans reported a lower positive predictive value (0.26) of an upper cut-off (0.67) to rule in, compared with the original study, along with a high proportion of the gray zone (35.5%) [ 12 ]. Given that the diagnostic performance of biomarkers depends on different clinical settings, the major implication of the FAST score in the present study could be the confirmatory exclusion of patients with high-risk or fibrotic NASH based on the lower cut-off [ 13 ]. Another concern in relation to the FAST score seems to be its inherently high dependency on AST levels, considering that most patients with advanced liver fibrosis on biopsy present with normal aminotransferase levels [ 14 ].…”

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“…6 Although comparative studies are lacking, combination strategies may increase overall accuracy and further reduce unnecessary liver biopsies. Finally, external validation in specific clinical settings in which NAFLD is frequently encountered, such as general practice, diabetes, obesity, and hypertension clinics, 7 is crucial to create efficient and cost-effective referral pathways to specialists for initiating specific treatment.…”