In this study, we explored the value of the liver stiffness assessed by 2D-SWE in predicting hypersplenism in the WD patients. Our study demonstrates that the assessment of liver stiffness using 2D-SWE is an effective approach for prospective prediction of hypersplenism in the WD patients. Furthermore, WD patients with a liver stiffness ≥ 10.45 kPa have a significantly higher risk of hypersplenism that might develop in a relatively short term. These findings enable prompt stratification of WD patients with high or low risk of hypersplenism.
In our study, the age of the patient, the diameter of portal vein, and the liver stiffness were independent risk factors for hypersplenism in the WD patients. Furthermore, the liver stiffness showed a higher AUC value of 0.817 when compared with that of the age and the diameter of portal vein. In one study in which 4D flow MRI was used to predict the occurrence of hypersplenism in 20 patients, Keller et al found that the AUC value for blood flow of splenic artery was 0.792 [18], which was slightly lower than that of liver stiffness reported in our study. MR imaging requires contrast agent injection, carries a high cost, and excludes patients with incompatible implanted devices. Most importantly, patients affected with WD typically develop neurological and psychiatric symptoms during disease progression and cannot tolerate MRI examination, making MRI a nonideal modality for assessment of WD patients. Our study suggests that liver stiffness measured using 2D-SWE can be used to assess the risk of hypersplenism in WD patients with high effectiveness and feasibility.
WD is a copper metabolic dysfunction disease, excess copper deposition in the liver tissues causes hepatocyte fatty degeneration, chronic inflammation, liver fibrosis and liver cirrhosis [19]. The pathological process of WD is consistent with other chronic liver diseases. The 2D-SWE is a two dimensions ultrasound-based technology for measuring tissue stiffness. It enables a real-time analysis of liver stiffness and can discover the underlying pathological processes of liver diseases. Recently, several studies demonstrate that liver stiffness assessed by 2D-SWE provide physicians with an alternative tool in terms of prediction of disease progression [14]. In a meta-analysis in which 746 patients with liver diseases were included, the study suggested that 2D-SWE could be used to forecast portal hypertension with the cutoffs of 15.2–24.6 kPa, with sensitivities raging from 78%-90% and specificities varying from 83%-89% [20]. Our study found that the cut-off value of liver stiffness was 10.45 KPa in predicting hypersplenism in WD patients, with a sensitivity of 75.9% and specificity of 73.8%. The discrepancy in the cutoff value can be partially explained by the difference of the average age of patients enrolled in the two studies. The average age of the 746 patients in the meta-analysis was 53–71 years old, which were older than that of our study (29.8 years old). Of note, so far, no studies have used 2D-SWE to predict hypersplenism in the patients with WD patients. It is possible that liver diseases, such as virus hepatitis, may usually complicated with portal hypertension, while, the probability of concurrent hypersplenism is not as high as WD [3, 4].
When compared with patients with liver stiffness < 10.45 KPa, those with liver stiffness ≥ 10.45 kPa had increased risk of hypersplenism (RR = 1.385). It was worth noting that, in additional to a relatively higher incidence of hypersplenism (57.9% vs. 13.5%), the median time period between baseline and the time points of hypersplenism development in the high-risk patients with liver stiffness ≥ 10.45 kPa was significantly shorter (20 months vs. 14 months, P < 0.001). These results implied that high risk patients may occur hypersplenism at a relatively short term. Our study highlighted that liver stiffness assessed by 2D-SWE can be applied to monitor liver progression of WD patients by stratifying risk of hypersplenism.
There were several limitations in the study. In view of the rare occurrence of WD, the results of this study are only based on one hospital, with a lack of multicenter liver elasticity data. Moreover, the study investigated the laboratory indicators but only FIB-4 and APRI were included for analyses. FIB-4 and APRI are commonly used for monitoring liver fibrosis in chronic hepatitis B and C as well as WD [21]. Whether the prediction efficacy of 2D-SWE will be affected when more laboratory indicators are added in the research needs further investigation.