###### Abstract  
Fibrosis-4 (FIB4), transient elastography (TE), and acoustic radiation force impulse (ARFI) are popular modalities to assess liver fibrosis. Their cutoff values for degrees of fibrosis vary between studies. The influence of hepatic steatosis on fibrosis measurements for different etiologies was evaluated. Data from a consecutive series of patients who received fibrosis measurement were included for the training group. An additional series with histology served as the validation group. A standardized protocol was performed for both TE and ARFI, mostly by a single technician. Patients with alcoholism, autoimmune disease, active inflammation, or who were receiving therapy were excluded. The training group included 215 patients and the validation group included 221. The correlation of liver stiffness between TE and ARFI was good (R\({}^{2}\) linear = 0.798; \(p<0.001\)). Different correlations between ARFI and TE were noted between high and low control attenuation parameter (CAP) values (cutoff: 290 dB/m), especially in the non-hepatitis B subgroups. Relatively lower FIB4 and TE values were seen in the high CAP versus low CAP in patients with histology-proven non-alcoholic fatty liver disease and chronic hepatitis C. FIB4 cutoff values were \(>\)25% lower among F2-F4 stages and the TE cutoff value for F4 was 8.5% lower in the high versus low CAP group. Such findings were not observed in chronic hepatitis B. Different fibrogenesis mechanisms between hepatitis B and non-B are discussed. We conclude that hepatic steatosis significantly impacts FIB4 and TE fibrosis measurements in non-hepatitis B-related liver diseases. Fibrosis grade should be interpreted with caution in severe steatosis. acoustic radiation force impulse imaging; transient elastography; liver fibrosis; liver steatosis; viral hepatitis +
Footnote †: journal: Applied  
expectancy can be markedly reduced. Subjects with moderate fibrosis is generally an indication for specific therapy to prevent liver cirrhosis. The gold standard for liver fibrosis evaluation is a liver biopsy. However, a biopsy is an invasive procedure with risks of bleeding, infection or organ injury. Many non-invasive methods have been developed for the evaluation of liver fibrosis. The fibrosis-4 (FIB4) index, transient elastography (TE) and acoustic radiation force impulse (ARFI) imaging are the three most popular non-invasive modalities for the assessment of liver fibrosis [1; 2; 3; 4; 5]. However, the cutoff values for fibrosis staging vary between institutes and liver disease etiologies (Supplementary Table S1). These three modalities are generally well-correlated, but they each have different advantages and limitations. FIB4 is calculated from routine laboratory data in addition to age [6]. It is inexpensive but has a relatively low area under the receiver operating characteristic curve (AUROC) values [7]. TE measurement by FibroScan (Echosens, Paris, France) is a well-standardized modality for the measurement of both liver fibrosis and steatosis [8; 9; 10]. Although the AUROC, sensitivity, and specificity of TE are all excellent, with values near 0.9 for the diagnosis of Hepatitis C Virus (HCV)-related liver cirrhosis [1; 10; 11], a considerable failure rate in the presence of obesity has been well documented [12]. The FibroScan XL probe was designed to overcome this issue; however, selecting between the FibroScan M and XL probes remains a problem, as does comparing data collected between the two probes [8; 13; 14; 15; 16]. In addition, without guided imaging, the measurements may be misleading if focal lesions in the right hepatic lobe are present [17]. In contrast, ARFI enables the selection of an optimal location for measurements. However, the study protocol for ARFI is relatively poorly standardized, and there are concerns regarding inter-observer and inter-location variation [18]. It should be noted that conventional ultrasound is also useful in screening for liver cirrhosis [19; 20].