Steatosis Severity Affects the Diagnostic Performances of Noninvasive Fibrosis Tests in Nonalcoholic Fatty Liver Disease

Sae Kyung Joo; Won Kim; Donghee Kim; Jung Ho Kim; Sohee Oh; Kook Lae Lee; Mee Soo Chang; Yong Jin Jung; Young Ho So; Myoung Seok Lee; Jeong Mo Bae; Byeong Gwan Kim


Liver International. 2018;38(2):331-341. 

In This Article

Abstract and Introduction


Background & Aims Nonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of heterogeneous metabolic subtypes. This study compared the diagnostic performances of noninvasive fibrosis tests in predicting advanced fibrosis among patients with NAFLD and examined the effects of the subgroups on their diagnostic performances.

Methods Three hundred fifteen patients with biopsy-proven NAFLD were prospectively enrolled. Acoustic radiation force impulse imaging (ARFI) was performed to obtain liver stiffness measurements (LSMs). The aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis 4 index (FIB-4), NAFLD fibrosis score (NFS) and BARD score were calculated. The diagnostic performances of noninvasive fibrosis tests were evaluated using the area under the receiver operating characteristic curve (AUROC).

Results Fibrosis 4 index (FIB-4) showed the highest AUROC for advanced fibrosis (0.866; 95% CI, 0.811–0.922). AUROC subgroup analyses were performed to assess the effects of the subgroups on diagnostic performance. For patients with advanced fibrosis, the APRI, BARD, FIB-4 and NFS AUROCs were significantly different among the radiological steatosis grades. Additionally, the AUROC of ARFI tended to decrease with increasing radiological steatosis severity. FIB-4 and NFS showed significantly lower AUROCs for advanced fibrosis in obese NAFLD than in nonobese NAFLD (P = .002 and P < .001 respectively). However, only radiological steatosis severity was independently associated with advanced fibrosis in multivariable analysis.

Conclusions Steatosis severity may affect the diagnostic performances of noninvasive fibrosis tests in patients with NAFLD. The application of different tools should be tailored for various NAFLD subgroups to optimize noninvasive fibrosis assessments.


Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in most of the world, particularly in developed countries.[1] The prevalence of NAFLD has been estimated to range from 6.3% to 33%, with a median of 20% in the general population.[2] In Asian countries, recent reports have revealed an increasing trend in NAFLD prevalence.[3,4]

Nonalcoholic fatty liver disease has rapidly become a major health burden because of the increasing severity of the obesity epidemic and the potential of NAFLD to progress to liver fibrosis, cirrhosis and hepatocellular carcinoma.[5] The mainstream strategies for managing NAFLD are to conduct regular follow-up visits, lifestyle modifications, and the early detection of liver fibrosis.[6] In particular, the accurate assessment of liver fibrosis is essential for predicting the long-term outcomes of patients with NAFLD.[7]

To date, liver biopsy has been regarded as the "gold standard" for the diagnosis and assessment of liver fibrosis. However, the procedure is expensive, invasive and has certain limitations. Therefore, liver biopsy is no longer considered the obligatory and primary screening method to obtain a diagnosis of NAFLD.[8–11] Alternatively, a variety of noninvasive serum indices of fibrosis are gradually replacing liver biopsy in clinical practice. Moreover, elastography-based mechanical indicators of fibrosis have also been widely used for the assessment of fibrosis in patients with NAFLD.

Noninvasive fibrosis tests such as serum fibrosis indices and liver stiffness measurements (LSMs) may have differential roles in predicting fibrosis in patients with various metabolic subtypes of NAFLD. Therefore, the aims of this study were to evaluate the diagnostic performances of noninvasive fibrosis tests and to identify the clinical or metabolic parameters that affect their ability to predict advanced fibrosis in patients with NAFLD.