Heather Mary-Kathleen Kosick1, Aline Keyrouz2, Oyedele Adeyi3, Giada Sebastiani2, Keyur Patel4. 1. Division of Gastroenterology, University Health Network Toronto, Toronto General Hospital, 200 Elizabeth Street, Toronto, ON, M5G 2C4, Canada. heather.evans@medportal.ca. 2. Division of Gastroenterology and Hepatology, McGill University Health Center, 1001 Decarie Blvd, Montreal, QC, H4A 3J1, Canada. 3. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, 55455, USA. 4. Division of Gastroenterology, University Health Network Toronto, Toronto General Hospital, 200 Elizabeth Street, Toronto, ON, M5G 2C4, Canada.
Abstract
BACKGROUND AND AIMS: Advanced F3-4 fibrosis predicts liver-related mortality in nonalcoholic fatty liver disease (NAFLD). Noninvasive tests, designed to rule in/out advanced fibrosis, are limited by indeterminates, necessitating biopsy. We aimed to determine whether stepwise combinations of noninvasive serum-based tests and elastography (VCTE) could predict F3-4, reduce indeterminates, and decrease liver biopsies. METHODS AND RESULTS: Five hundred forty-one biopsy-proven NAFLD cases were identified between 2010 and 2018 from two Canadian centers. Characteristics of training (n = 407)/validation (n = 134) cohorts included: males 54%/59%; mean age 48.5/52.5 years; mean body mass index 32.3/33.6 kg/m2; diabetes mellitus 30%/34%; and F3-4 48%/43%. For training/validation cohorts, area under the receiver operating curve (AUROC) for FIB-4, AST-platelet ratio index (APRI), NAFLD fibrosis score (NFS), BARD score, and AST/ALT ratio ranged from 0.70 to 0.83/0.68 to 0.81, with indeterminates 25-39%/34-45%, for F3-4. In the training cohort, parallel FIB-4 + NFS had good accuracy (AUROC = 0.81) but was limited by 38% indeterminates and 16% misclassified. Sequential FIB-4 → NFS reduced indeterminates to 10%, and FIB-4 → VCTE to 0%, misclassified 20-22%, while maintaining high specificity (0.88-0.92) and accuracy (AUROC 0.75-0.78) for combined cohorts. Liver biopsy could have been avoided in 27-29% of patients using sequential algorithms. CONCLUSIONS: Sequential FIB-4 ➔ NFS/VCTE predicts F3-4 with high specificity and good accuracy, while reducing indeterminates and need for biopsy. Parallel algorithms are limited by high indeterminates. Sequential FIB-4 ➔ NFS had similar accuracy to VCTE-containing algorithms. Validation in low-prevalence cohorts may allow for potential use in community or resource-limited areas for risk stratification.
BACKGROUND AND AIMS: Advanced F3-4 fibrosis predicts liver-related mortality in nonalcoholic fatty liver disease (NAFLD). Noninvasive tests, designed to rule in/out advanced fibrosis, are limited by indeterminates, necessitating biopsy. We aimed to determine whether stepwise combinations of noninvasive serum-based tests and elastography (VCTE) could predict F3-4, reduce indeterminates, and decrease liver biopsies. METHODS AND RESULTS: Five hundred forty-one biopsy-proven NAFLD cases were identified between 2010 and 2018 from two Canadian centers. Characteristics of training (n = 407)/validation (n = 134) cohorts included: males 54%/59%; mean age 48.5/52.5 years; mean body mass index 32.3/33.6 kg/m2; diabetes mellitus 30%/34%; and F3-4 48%/43%. For training/validation cohorts, area under the receiver operating curve (AUROC) for FIB-4, AST-platelet ratio index (APRI), NAFLDfibrosis score (NFS), BARD score, and AST/ALT ratio ranged from 0.70 to 0.83/0.68 to 0.81, with indeterminates 25-39%/34-45%, for F3-4. In the training cohort, parallel FIB-4 + NFS had good accuracy (AUROC = 0.81) but was limited by 38% indeterminates and 16% misclassified. Sequential FIB-4 → NFS reduced indeterminates to 10%, and FIB-4 → VCTE to 0%, misclassified 20-22%, while maintaining high specificity (0.88-0.92) and accuracy (AUROC 0.75-0.78) for combined cohorts. Liver biopsy could have been avoided in 27-29% of patients using sequential algorithms. CONCLUSIONS: Sequential FIB-4 ➔ NFS/VCTE predicts F3-4 with high specificity and good accuracy, while reducing indeterminates and need for biopsy. Parallel algorithms are limited by high indeterminates. Sequential FIB-4 ➔ NFS had similar accuracy to VCTE-containing algorithms. Validation in low-prevalence cohorts may allow for potential use in community or resource-limited areas for risk stratification.
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