An algorithm for quantitative ultrasound steatometry of the liver: development of the technique and evaluation of its sensitivity, specificity, and reproducibility

Rationale: Due to rising prevalence of metabolic syndrome, obesity and type 2 diabetes mellitus, the prevalence of metabolic-associated hepatic steatosis has amounted to 38–42% worldwide. The burden of its dangerous complications, such as steatohepatitis, liver fibrosis and cirrhosis, hepatocellular carcinoma, make the search for effective diagnostic methods of liver steatosis a priority. However, lack standardization of assessments reduces the accuracy and reproducibility of their results and requires elaboration of unified protocols for such assessments. Aim: To develop a unified algorithm for quantitative ultrasound steatometry of the liver and to evaluate its diagnostic accuracy (sensitivity, specificity, and reproducibility). Methods: This was a three step study, with its 1st part including 34 specialists on echography diagnostics aged 28 to 64 years with varying levels of experience (1 to 3 years, n = 5, 15.6%; 4 to 10 years, n = 18, 50%; 11 to 20 years, n = 8, 25%; ≥ 21 years: n = 3, 9.4%). The accuracy of quantitative ultrasound steatometry procedure evaluated with a test questionnaire, by analysis of archived echograms (340 clinical cases), and real-time ultrasound steatometry performed in 102 patients under the direct or remote supervision of the authors. In the 2nd part of the study we examined 173 patients with liver steatosis confirmed by multiparametric echography, comprehensive clinical and biochemical SteatoTest, magnetic resonance spectroscopy, multiaxial computed tomography with color mapping, dual-energy X-ray absorptiometry in the "whole body" mode, and histological examination of liver biopsy samples. In the 3rd part of the study we assessed the reproducibility of the quantitative ultrasound steatometry algorithm proposed by the authors, 12 ultrasound diagnostic physicians with varying levels of experience were involved (1 to 3 years: n = 3; 4 to 10 years: n = 3; 11 to 20 years: n = 3; more than 21 years: n = 3). Each physician examined 20 patients (5 patients in groups with no steatosis and with histologically confirmed steatosis of grades 1 to 3). Results: In the 1st part of the study, we identified the main patterns of quantitative ultrasound steatometry of the liver by specialists in the ultrasound diagnostics. Based on the international and Russian guidelines, as well as our own research, we proposed standardized operational procedure for quantitative ultrasound steatometry. The comparative analysis in the 2nd part of the study showed that the implementation of the operational procedure proposed by the author was associated with more narrow intervals for the ultrasound wave attenuation coefficient and better reproducibility, compared to the most common “rules” used by specialists in the ultrasound diagnostics. There were significant differences in the diagnosis of moderate and maximal steatosis with these two approaches (p 0.05). The sensitivity and specificity of the operational procedure proposed by the authors were 89% and 94%, respectively, compared to 75% and 79% for the commonly used approach. In the 3rd part of the study, there were no significant differences in the ultrasound wave attenuation coefficient measured by specialists with various levels of experience according to the authors’ algorithm. The inter-rater correlation coefficient was 0.948 (95% confidence interval [0.914; 0.973], p 0.001), confirming the authors method's high reproducibility and consistency. Conclusion: We have proposed an operational procedure for ultrasound quantitative steatometry of the liver, based on determination of the attenuation coefficient of the ultrasound wave in tissues. The implementation of this algorithm by medical specialists irrespective of their working experience provides high reproducibility of the method, with maximal sensitivity (89%) and specificity (94%).