Background/Aims: Advanced fibrosis (F≥3) indicates poor outcomes in nonalcoholic fatty liver disease (NAFLD). Here, we examined the diagnostic performance of the fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) for detecting (or excluding) advanced fibrosis in patients with biopsy-proven NAFLD. Methods: The diagnostic performance of each noninvasive test according to previously identified cutoff points indicating low and high risk for advanced fibrosis was determined in 463 patients with NAFLD. Patients who scored <1.3 and >2.67 on the FIB-4 were considered at low and high risk for advanced fibrosis, respectively. Patients who scored <-1.455 and >0.676 on the NFS were considered at low and high risk for advanced fibrosis, respectively. Results: Eightyone patients (17.5%) had biopsy-proven advanced fibrosis (F≥3). The published FIB-4 cutoff values for low and high risk were able to exclude advanced fibrosis with negative predictive values (NPVs) of 0.907 and 0.843 and specificities of 74% and 97%, respectively. The published NFS cutoff values for low and high risk were able to exclude advanced fibrosis with NPVs of 0.913 and 0.842 and specificities of 63% and 96%, respectively. If biopsies were performed in only patients with a FIB-4 above the low cutoff point (≥1.3), 67.1% could be avoided. Conversely, if biopsies were performed in only patients with an NFS above the low cutoff point (≥-1.455), 57.0% could be avoided. Conclusions: The main clinical utility of the FIB-4 and NFS in patients with NAFLD lies in the ability to exclude, not identify, advanced fibrosis.

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Nonalcoholic fatty liver disease (NAFLD) is a multisystemic clinical condition that presents with a wide spectrum of extrahepatic manifestations, such as obesity, type 2 diabetes mellitus, metabolic syndrome, cardiovascular diseases, chronic kidney disease, extrahepatic malignancies, cognitive disorders, and polycystic ovarian syndrome. Among NAFLD patients, the most common mortality etiology is cardiovascular disorders, followed by extrahepatic malignancies, diabetes mellitus, and liver-related complications. Furthermore, the severity of extrahepatic diseases is parallel to the severity of NAFLD. In clinical practice, awareness of the associations of concomitant diseases is of major importance for initiating prompt and timely screening and multidisciplinary management of the disease spectrum. In 2020, a consensus from 22 countries redefined the disease as metabolic (dysfunction)-associated fatty liver disease (MAFLD), which resulted in the redefinition of the corresponding population. Although the patients diagnosed with MAFLD and NAFLD mostly overlap, the MAFLD and NAFLD populations are not identical. In this review, we compared the associations of key extrahepatic diseases between NAFLD and MAFLD.

Background and aim While non-invasive scores are increasingly being used to screen for advanced fibrosis in metabolic (dysfunction) associated fatty liver disease (MAFLD), the effect of BMI on their clinical utility remains uncertain. This study assessed the usefulness of the Fibrosis-4 index (FIB-4) and the non-alcoholic fatty liver disease fibrosis score (NFS) in lean, overweight, obese, severely obese, and morbidly obese patients with biopsy-proven MAFLD. Methods A total of 560 patients (28 lean, 174 overweight, 229 obese, 89 severely obese, 40 morbidly obese) were included. Diagnostic performances and optimal cut-off values for FIB-4 and NFS were calculated using receiver operating characteristic (ROC) curve analysis. ResultsIn both lean and morbidly obese patients with MAFLD, both FIB-4 and NFS failed to discriminate advanced fibrosis. Conversely, both scores showed acceptable diagnostic performances in exclusion of advanced fibrosis in overweight, obese, and severely obese patients. FIB-4 was able to exclude advanced fibrosis with the highest diagnostic accuracy in the subgroup of overweight patients (area under the ROC curve: 0.829, 95% confidence interval: 0.738−0.919). Conclusion FIB-4 and NFS can confidently be used to exclude advanced fibrosis in overweight, obese, and severely obese patients. However, they do not appear clinically useful in lean and morbidly obese patients.

Background and Aim: Noninvasive scores are developed for the estimation of advanced fibrosis, including parameters in addition to transaminases in non-alcoholic fatty liver disease (NAFLD). In this study, we aimed to investigate the diagnostic performances of Fibrosis-4 (FIB-4) and NAFLD Fibrosis Score (NFS) in the estimation of advanced fibrosis comparing patients with normal and elevated transaminases. Material and Methods: We retrospectively analyzed the prospectively collected data of a total of 407 consecutive patients with biopsy-proven NAFLD. FIB-4 scores of <1.3 and >2.67 or <1.45 and >3.25 indicated a low and high risk for advanced fibrosis, respectively. NFS scores of <-1.455 and >0.676 were used to assess low and high risk for advanced fibrosis, respectiv. Results: FIB-4 cutoffs of <1.3 and <1.45 for low risk of advanced fibrosis had a sensitivity of 70% and 54% in patients with elevated transaminases and 70% and 52% in patients with normal transaminases, respectively. The specificities for the cutoffs of >2.67 and >3.25 were 97% and 98% in patients with elevated transaminases and 99% and 100% in patients with normal transaminases, respectively. Concerning NFS, we found similar results. Conclusion: FIB-4 and NFS showed acceptable diagnostic performance in the exclusion of advanced fibrosis in both populations with normal and elevated transaminases.