Elucidation of Idiopathic Portal Hypertension Based on Liver and Spleen Stiffness Measurements by Virtual Touch Tissue Quantification and Peripheral Blood CD4+ CD25+ T Cytometry

Abstract

[Introduction] Virtual Touch Tissue Quantification (VTTQ) is an ultrasound technique to quantify tissue stiffness based on measurement of the propagation velocity of elastic shearwaves (Vs) generated by acoustic radiation force impulses that cause tissue displacements. [Objective] To explore the usefulness of liver and spleen stiffness measurements by VTTQ for diagnostic differentiation between idiopathic portal hypertension (IPH) and portal hypertension caused by liver cirrhosis (LC). [Subjects] Thirteen patients with histologically diagnosed IPH and 18 patients with histologically diagnosed LC were recruited for this study. Eight normal subjects (NC) and 7 patients with chronic hepatitis (CH) were also included. [Methods] With the region of interest (ROI) set at a 3-cm depth from the body surface, the mean of 5 successful Vs measurements of the liver and spleen in each patient was determined. The percentage of peripheral blood CD4+ CD25+ T cells (Tregs) in the LC cases and IPH cases was analyzed by FACS, and the size of the spleen (SI) was also measured. [Results] The measured stiffness of the liver (NC: CH: LC: IPH = 1.14: 1.40: 2.50: 1.56 m/s) was greater in the LC patients (p < 0.001), and that of the spleen (2.03: 2.30: 3.12: 3.90) was greater in the patients with IPH (p < 0.001). Making each ROC curve, we set the cut-off values of liver stiffness by VTTQ as follows (CH: LC: IPH = 1.14: 1.54: 1.23 m/s). The sensitivities were (89.5: 94.7: 89.5%) and the specificities were (62.5: 100.0: 75.0%). Meanwhile, setting the cut-off values of spleen stiffness as follows (CH: LC: IPH = 2.44: 2.61: 2.88 m/s), the sensitivities were (66.7: 90.5: 90.5%) and the specificities were (87.5: 100.0: 100.0%). The stiffness measurements of both liver and spleen were proved to be useful in diagnosis. Furthermore, a lower peripheral blood Tregs frequency [(LC: IPH) = (19.0: 11.6%)] (p < 0.001) and a larger SI (22.5: 44.5) (p < 0.001) were recorded in the IPH patients. [Discussion] The IPH patient group showed a lower liver stiffness relative to the LC group and comparable liver stiffness to that in the CH group. Stiffness of the spleen, nevertheless, was markedly higher in the IPH group; thus, stiffness measurements of both the liver and spleen allowed ready diagnostic differentiation between portal hypertension associated with LC and IPH. The increased splenic stiffness with splenomegaly in IPH was considered to be attributable to a state of enhanced immune functions when viewed with reference to the reduced percentage of peripheral blood Tregs.