期刊
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
卷 107, 期 5, 页码 E2008-E2020出版社
ENDOCRINE SOC
DOI: 10.1210/clinem/dgab933
关键词
nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; fibrosis; cirrhosis; biomarkers; obesity
资金
- Academy of Finland [309263]
- Novo Nordisk Foundation
- Sigrid Juselius Foundation
- Orion Research Foundation sr
- Yrjo Jahnsson Foundation sr
- Maud Kuistila Memorial Foundation sr
- Emil Aaltonen Foundation sr
- Italian Ministry of Health (Ministero della Salute, Ricerca Finalizzata) [RF-2016-02364358]
- Ricerca Corrente Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
- Fondazione IRCCS Ca' Granda core COVID-19 Biobank [RC100017A]
- Fondazione IRCCS Ca' Granda Liver BIBLE [PR-0391]
- Academy of Finland (AKA) [309263, 309263] Funding Source: Academy of Finland (AKA)
This study investigated the impact of obesity on the performance of liver fibrosis biomarkers in NAFLD and found that ADAPT and FIB-4 are the best-performing biomarkers in obese patients, unaffected by body mass index.
Context: Guidelines recommend blood-based fibrosis biomarkers to identify advanced nonalcoholic fatty liver disease (NAFLD), which is particularly prevalent in patients with obesity. Objective: To study whether the degree of obesity affects the performance of liver fibrosis biomarkers in NAFLD. Design: Cross-sectional cohort study comparing simple fibrosis scores [Fibrosis-4 Index (FIB-4); NAFLD Fibrosis Score (NFS); aspartate aminotransferase to platelet ratio index; BARD (body mass index, aspartate-to-alanine aminotransferase ratio, diabetes); Hepamet Fibrosis Score (HFS)] and newer scores incorporating neo-epitope biomarkers PRO-C3 (ADAPT, FIBC3) or cytokeratin 18 (MACK-3). Setting: Tertiary referral center. Patients: We recruited overweight/obese patients from endocrinology (n = 307) and hepatology (n = 71) clinics undergoing a liver biopsy [median body mass index (BMI) 40.3 (interquartile range 36.0-44.7) kg/m(2)]. Additionally, we studied 859 less obese patients with biopsy-proven NAFLD to derive BMI-adjusted cutoffs for NFS. Main Outcome Measures: Biomarker area under the receiver operating characteristic (AUROC), sensitivity, specificity, and predictive values to identify histological stage >= F3 fibrosis or nonalcoholic steatohepatitis with >= F2 fibrosis [fibrotic nonalcoholic steatohepatitis (NASH)]. Results: The scores with an AUROC >= 0.85 to identify >= F3 fibrosis were ADAPT, FIB-4, FIBC3, and HFS. For fibrotic NASH, the best predictors were MACK-3 and ADAPT. The specificities of NFS, BARD, and FIBC3 deteriorated as a function of BMI. We derived and validated new cutoffs for NFS to rule in/out >= F3 fibrosis in groups with BM Is <30.0, 30.0 to 39.9, and >= 40.0 kg/m(2). This optimized its performance at all levels of BMI. Sequentially combining FIB-4 with ADAPT or FIBC3 increased specificity to diagnose >= F3 fibrosis. Conclusions: In obese patients, the best-performing fibrosis biomarkers are ADAPT and the inexpensive FIB-4, which are unaffected by BMI. The widely used NFS loses specificity in obese individuals, which may be corrected with BMI-adjusted cutoffs.
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