This prospective study clearly presents that 2D-SWE is a useful non-invasive tool for evaluating the degree of liver fibrosis in clinical practices, as well as being more effective in determining advanced fibrosis than either FIB-4 or APRI. In this prospective pathology-based study, all study subjects underwent the liver biopsy and 2D-SWE examination on the same day, so the bias in previous studies of 2D-SWE, such as lacking a pathology standard reference24 or an up to 24-week interval between liver biopsy and 2D-SWE examination25, could have been well overcome. Although there are fewer studies of 2D-SWE than there are of other modalities in evaluating liver fibrosis, the results of this study provide solid data that 2D-SWE can be implemented as another non-invasive alternative in clinical practices.
Several non-invasive tests have been used for the evaluation of liver fibrosis; however some disadvantages may limit their applications. Although FIB-4 and APRI have been widely used to predict advanced liver fibrosis because of being non-invasive, cheap, and convenient, the sensitivity and specificity of FIB-4 and APRI have not been satisfactory. Both FIB-4 and APRI were initially established to predict advanced fibrosis in patients with chronic hepatitis C; however in a previous study, the fibrosis status could not be determined in a significant proportion of patients (35.4% in FIB-4 and 49% in APRI)22, 23. In a recently published study examining the diagnostic performance of FIB-4 and APRI in cirrhotic patients with chronic hepatitis B, a lower AUROC in FIB-4 (0.75) and APRI (0.65) was also reported26. In addition, although TE has been proven to be superior to APRI in the evaluation of liver fibrosis, its measurements were proved to be less reproducible in patients with fatty liver disease, obesity, and ALT elevation27. Furthermore, the diagnostic performance of TE has been found to be inferior to that of 2D-SWE in predicting advanced fibrosis in a meta-analysis study28. Although ARFI has fewer limitations than TE29, its accuracy also decreases in patients with fatty liver disease29, 30. In this study, the diagnostic performance of 2D-SWE was validated not only within the whole patient cohort experiencing various liver disorders, but also in the individual patient subgroups. 2D-SWE may well be an easy-to-use tool for effectively accessing patients with various liver conditions.
Although there have been several studies in recent years involving 2D-SWE for the purpose of evaluating liver fibrosis, most of them were retrospective studies. The measurement of 2D-SWE and the performing of a liver biopsy were usually not conducted on the same day, with the time interval possibly being up to 12 weeks31,32. In this situation, the severity of liver fibrosis may have changed during this period. Importantly, the liver area selected for a 2D-SWE measurement might be different from that chosen for a liver biopsy, with the data taken from the 2D-SWE possibly not being representative of the pathology findings. In this pathology-based prospective study, the data regarding the 2D-SWE measurements and blood tests were collected right before the liver biopsy, with the liver specimens acquired from the area selected for 2D-SWE measurement. The possible bias which occurred in previous 2D-SWE studies has been minimized in this study. In addition, data regarding 2D-SWE in a patient cohort, including various liver disorders, remains limited. Most previous 2D-SWE studies were conducted in East Asian countries, and the reported data basically investigated from patients with chronic HBV infection14,33. On the other hand, studies which have been carried out in Western countries mainly focused on patients with chronic HCV infection34. In this study which included patients with various liver disorders, 2D-SWE presented a good diagnostic performance not only in the whole patient cohort, but also in patients with various liver disorders.
Several limitations should be acknowledged in this study. First, the sample size of our study was not large enough to confidently evaluate the accuracy of 2D-SWE in all patient subgroups, such as patients with alcoholic liver disease or autoimmune liver disease. A larger study for investigating other patient subgroups should be conducted in the future. Second, most patients recruited for this study had been infected with HBV and/or HCV, therefore patients without chronic viral hepatitis should be interpreted with caution. For example, although this study demonstrated that the diagnostic performance of 2D-SWE was not interfered in patients with concurrent fatty liver disease, subgroup analysis for patients experiencing purely fatty liver disease could not be conducted due to the small sample size. Although the strong diagnostic performance of 2D-SWE in non-alcoholic liver disease has been reported in a recent small study35, further validation studies for patients without chronic viral hepatitis should be encouraged. Third, this has been a study conducted in Taiwan, and the data of this study would need to be validated in Western countries.
In conclusion, 2D-SWE can be widely used as an effective non-invasive tool for the diagnosis of advanced liver fibrosis in patients with various liver disorders.
All relevant data has been reported within the manuscript. Further supplementary datasets can be obtained upon written request addressed to the corresponding author.