FIB-4 IS MORE ACCURATE THAN FIBROSCAN IN PREDICTING ADVANCED FIBROSIS AT HIGHER STAGES OF BODY MASS INDEX

Background: Current non-invasive tests (NITs) utilized to screen and predict liver fibrosis were developed in predominantly Caucasian populations, and their performance in non-Caucasians is not well known. The purpose of this study is to evaluate the performance of NITs compared to Transient Elastography (TE) across different ethnic groups from a large diverse national dataset.

Methods: Data were derived from the National Health and Nutrition Examination Surveys (NHANES) 2017-2020, which included a total of 7,767 adults with valid TE measurements. Participants with excessive alcohol consumption, alternative etiologies of liver disease, and/or steatogenic medications were excluded. Patients of multiracial origin or without ethnic information were also excluded. Liver stiffness measurements ≥12 kPa were used to define presence of advanced fibrosis. Performance of the Fibrosis-4 (FIB-4) Index, NAFLD Fibrosis Score (NFS) and the AST to Platelet Ratio Index (APRI) were assessed by calculating the area under the receiver operator characteristic curves (AUROC).

Results: A total of 6,294 adults were included. Participant demographics are shown in Table 1. The prevalence of advanced fibrosis was 3.0% in the overall population based on TE. Prevalence of advanced fibrosis was higher in Caucasian and Mexican-American participants compared to non-Hispanic Black and Asian participants (3.9% vs. 3.5% vs. 2.1% vs. 1.7%, respectively, p=0.003). The FIB-4 and APRI performed significantly worse in non-Hispanic Blacks compared to other ethnicities (Table 2). FIB-4 performed significantly better in Mexican-American and Asian participants and APRI had the highest AUROC among Asian participants. The NFS performed similarly across all ethnicities (Table 2) but tended to overestimate fibrosis in all groups compared to TE. Further analysis revealed that among participants with advanced fibrosis, non-Hispanic Black participants had significantly lower plasma AST and ALT compared to all other ethnic groups. No differences were observed in age, platelets, or albumin in non-Hispanic Black participants with advanced fibrosis compared to other ethnic groups.

Discussion: In a large diverse national dataset, the performance of laboratory based NITs compared to TE showed significant differences across ethnic groups, with significant worse performance in non-Hispanic Blacks. Our findings suggest this may be related to non-Hispanic Blacks with advanced fibrosis having lower AST and ALT levels compared to other ethnic groups. Given that NITs are now widely recommended for use in screening patients for advanced fibrosis, it is imperative that the scores are equitable across ethnic groups. Prospective studies to validate these findings against liver biopsy are warranted.

Background
Recent literature raises concern that Fibroscan may be inaccurate in patients with elevated BMI and NAFLD/NASH. However, FIB-4 appears to perform well in accuracy regardless of BMI stage. Therefore, it is unclear whether existing algorithms of FIB-4 followed by Fibroscan for routine liver fibrosis screening performs well in patients with higher BMIs. We aimed to assess the degree of discordance between FIB-4 and Fibroscan stratified by BMI and how well either test performs relative to biopsy.

Methods
We performed a retrospective review of the National Health and Nutrition Examination Survey (NHANES) 2017 – March 2020 database. We included all patients between the age of 35-65 who had completed Fibroscan and lab testing sufficient to calculate FIB-4 (AST, ALT, and platelets). Patients who were pregnant, consumed excessive alcohol, or had Hepatitis B or C were excluded. The primary outcome was disagreement between FIB-4 and Fibroscan (i.e. if one test reported low risk for advanced fibrosis and the other test reported high risk). We used FIB-4 cutoffs of 1.3 and 2.67 to separate low, intermediate, and high risk for advanced fibrosis, and 9.7 kPa from Fibroscan to separate low and high risk. We then compared our findings to patients locally with biopsy-proven NAFLD/NASH. Statistical analysis was done with SAS 9.4.

Results
A total of 3085 patients from the NHANES database were included. Average age was 50.3 and 54.2% were female. Average BMI was 30.2. Patient demographics are included in Figure 1A and breakdown of % of patients in each FIB-4 and Fibroscan category are listed in 1B. There was overall 4.78% disagreement. Increasing BMI was significant associated with heightened disagreement, with only 0.87% disagreement at BMI<25 going up to 25.1% at BMI>40 [Figure 1C] and odds ratio of 1.15 for disagreement on logistical regression (1D, p<0.0001).

In comparison, at our center between 2018-2022, we included 241 patients. Average BMI was higher at 35.3 with higher FIB-4 and Fibroscan values [Figure 2A]. Disagreement occurred 23.7% of the time and trended similarly when stratified by BMI [Figure 2B]. Out of 57 cases in which disagreement occurred, 51 (89.5%) were due to Fibroscan calling high risk for advanced fibrosis whereas FIB-4 called low risk. In 43/57 (75.4%) cases, FIB-4 was more accurate, and the majority (95.3%) were due to Fibroscan inaccurately labelling advanced fibrosis. For the 82 patients with intermediate risk of advanced fibrosis on FIB-4, Fibroscan was incorrect in 25 (30.5%) cases [see Figure 2C for stratified by BMI].

Conclusions
Disagreement between FIB-4 and Fibroscan increased at higher BMIs, with FIB-4 being more accurate ¾ of the time. Most disagreement is due to Fibroscan overcalling advanced fibrosis. More nuanced algorithms for liver fibrosis screening may be warranted for patients with higher stages of obesity.