Aim The Enhanced Liver Fibrosis (ELF) test comprises a logarithmic algorithm combining three serum markers of hepatic extracellular matrix metabolism. We aimed to evaluate the performance of ELF for the diagnosis of liver fibrosis and to compare it with that of liver stiffness measurement (LSM) by FibroScan in non‐alcoholic fatty liver disease. Methods ELF cut‐off values for the diagnosis of advanced fibrosis were obtained using receiver operating characteristic analysis in patients with biopsy‐confirmed non‐alcoholic fatty liver disease (training set; n = 200). Diagnostic performance was analyzed in the training set and in a validation set (n = 166), and compared with that of LSM in the FibroScan cohort (n = 224). Results The area under receiver operating characteristic curve was 0.81 for the diagnosis of advanced fibrosis, and the ELF cut‐off values were 9.34 with 90.4% sensitivity and 10.83 with 90.6% specificity in the training set, and 89.8% sensitivity and 85.5% specificity in the validation set. There was no significant difference in the area under the receiver operating characteristic curve between ELF and LSM (0.812 and 0.839). A combination of ELF (cut‐off 10.83) and LSM (cut‐off 11.45) increased the specificity to 97.9% and the positive predictive value, versus ELF alone. Sequential use of the Fibrosis‐4 index (cut‐off 2.67) and ELF (cut‐off 9.34) increased the sensitivity to 95.9%. Conclusions ELF can identify advanced liver fibrosis in non‐alcoholic fatty liver disease, and its diagnostic accuracy is comparable to that of FibroScan. According to the clinical setting, combinations or sequential procedures using other non‐invasive tests complement the diagnostic performance of ELF for the identification of advanced fibrosis.

Access to imaging is limited for diagnosing nonalcoholic fatty liver disease (NAFLD) in general populations. This study evaluated the diagnostic performance of noninvasive and nonimaging indexes to predict NAFLD in the general Japanese population. Health checkup examinees without hepatitis virus infection or habitual alcohol drinking were included. Fatty liver was diagnosed by ultrasonography. The hepatic steatosis index (HSI), Zhejiang University (ZJU) index, and fatty liver index (FLI) were determined, and risk of advanced liver fibrosis was evaluated by the fibrosis-4 index. NAFLD was diagnosed in 1935 (28.0%) of the 6927 subjects. The area under the receiver operating characteristic (AUROC) curve of the HSI, ZJU index, and FLI was 0.874, 0.886, and 0.884, respectively. The AUROC of the ZJU index (p < 0.001) and FLI (p = 0.002) was significantly greater than that for the HSI. In subjects with a high risk of advanced fibrosis, the sensitivity of the HSI, ZJU index, and FLI were 88.8%, 94.4%, and 83.3% with a low cut-off value and the specificity was 98.5%, 100%, and 100% with a high cut-off value. In conclusion, all indexes were useful to diagnose NAFLD in the general Japanese population and in subjects with potentially advanced liver fibrosis.

The effect of the skin–capsular distance (SCD) on the controlled attenuation parameter (CAP) for diagnosis of liver steatosis in patients with nonalcoholic fatty liver disease (NAFLD) remains unclear. The SCD was measured using B-mode ultrasound, and the CAP was measured using the M probe of FibroScan®. According to the indications of the M probe, 113 patients with an SCD of ≤ 25 mm were included in the present study. The association between the SCD and CAP was investigated, and the diagnostic performance of the SCD-adjusted CAP was tested. The SCD showed the most significant positive correlation with the CAP (ρ = 0.329, p < 0.001). In the multiple regression analysis, the SCD and serum albumin concentration were associated with the CAP, independent of pathological liver steatosis. According to the multivariate analysis, two different formulas were developed to obtain the adjusted CAP using the SCD and serum albumin concentration as follows: adjusted CAP (dB/m) = CAP − (5.26 × SCD) and adjusted CAP (dB/m) = CAP − (5.35 × SCD) − (25.77 × serum albumin concentration). The area under the receiver operating characteristic curve for diagnosis of a steatosis score ≥ 2 of adjusted CAP was 0.678 and 0.684 respectively, which were significantly greater than the original CAP (0.621: p = 0.030 and p = 0.024). The SCD is associated with the CAP independent of liver steatosis. Adjustment of the CAP using the SCD improves the diagnostic performance of the CAP in NAFLD.

Background The effect of the skin–capsular distance (SCD) on the controlled attenuation parameter (CAP) for diagnosis of liver steatosis in patients with nonalcoholic fatty liver disease (NAFLD) remains unclear. Methods The SCD was measured using B-mode ultrasound, and the CAP was measured using the M probe of FibroScan®. According to the indications of the M probe, 113 patients with an SCD of ≤ 25 mm were included in the present study. The association between the SCD and CAP was investigated, and the diagnostic performance of the SCD-adjusted CAP was tested. Results The SCD showed the most significant positive correlation with the CAP (ρ = 0.329, p < 0.001). In the multiple regression analysis, the SCD was associated with the CAP independent of pathological liver steatosis. The adjusted CAP was calculated as follows: adjusted CAP (dB/m) = CAP − (5.26 × SCD). The area under the receiver operating characteristic curve for diagnosis of a steatosis score ≥ 2 was significantly greater for the adjusted CAP than original CAP. Conclusions The SCD is associated with the CAP independent of liver steatosis. Adjustment of the CAP using the SCD improves the diagnostic performance of the CAP in NAFLD.

There is an association between nonalcoholic fatty liver disease (NAFLD) and atherosclerosis, but the genetic risk of atherosclerosis in NAFLD remains unclear. Here, a single-nucleotide polymorphism (SNP) of the heat shock 70 kDa protein 8 (HSPA8) gene was analyzed in 123 NAFLD patients who had been diagnosed using a liver biopsy, and the NAFLD phenotype including the maximum intima–media thickness (Max-IMT) of the carotid artery was investigated. Patients with the minor allele (A/G or G/G) of rs2236659 showed a lower serum heat shock cognate 71 kDa protein concentration than those with the major A/A allele. Compared with the patients with the major allele, those with the minor allele showed a higher prevalence of hypertension and higher Max-IMT in men. No significant associations between the HSPA8 genotype and hepatic pathological findings were identified. In decision-tree analysis, age, sex, liver fibrosis, and HSPA8 genotype were individually associated with severe carotid artery atherosclerosis (Max-IMT ≥ 1.5 mm). Noncirrhotic men aged ≥ 65 years were most significantly affected by the minor allele of HSPA8. To predict the risk of atherosclerosis and cardiovascular disease, HSPA8 SNP genotyping might be useful, particularly for older male NAFLD patients.