학술논문
Obesity Modifies the Performance of Fibrosis Biomarkers in Nonalcoholic Fatty Liver Disease
Clinical Research Article
Clinical Research Article
Document Type
Academic Journal
Author
Qadri, Sami; Ahlholm, Noora; Lonsmann, Ida; Pellegrini, Paola; Poikola, Anni; Luukkonen, Panu K.; Porthan, Kimmo; Juuti, Anne; Sammalkorpi, Henna; Penttila, Anne K.; D'Ambrosio, Roberta; Soardo, Giorgio; Leeming, Diana J.; Karsdal, Morten; Arola, Johanna; Kechagias, Stergios; Pelusi, Serena; Ekstedt, Mattias; Valenti, Luca; Hagstrom, Hannes; Yki-Jarvinen, Hannele
Source
Journal of Clinical Endocrinology & Metabolism. May 2022, Vol. 107 Issue 5, pe2008, 13 p.
Subject
Language
English
ISSN
0021-972X
Abstract
Most patients with nonalcoholic fatty liver disease (NAFLD) are either overweight or obese (1). Obesity is a key predictor of advanced liver fibrosis (bridging fibrosis [stage F3] or cirrhosis [stage [...]
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.sup.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 dentify histological stage [greater than or equal to]F3 fibrosis or nonalcoholic steatohepatitis with [greater than or equal to]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 BMIs 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. Key Words: nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, fibrosis, cirrhosis, biomarkers, obesity
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.sup.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 dentify histological stage [greater than or equal to]F3 fibrosis or nonalcoholic steatohepatitis with [greater than or equal to]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 BMIs 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. Key Words: nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, fibrosis, cirrhosis, biomarkers, obesity