Chronic liver disease: noninvasive subharmonic aided pressure estimation of hepatic venous pressure gradient

Abstract

Purpose: To compare subharmonic aided pressure estimation (SHAPE) with pressure catheter-based measurements in human patients with chronic liver disease undergoing transjugular liver biopsy.

Materials and methods: This HIPAA-compliant study had U.S. Food and Drug Administration and institutional review board approval, and written informed consent was obtained from all participants. Forty-five patients completed this study between December 2010 and December 2011. A clinical ultrasonography (US) scanner was modified to obtain SHAPE data. After transjugular liver biopsy with pressure measurements as part of the standard of care, 45 patients received an infusion of a microbubble US contrast agent and saline. During infusion, SHAPE data were collected from a portal and hepatic vein and were compared with invasive measurements. Correlations between data sets were determined by using the Pearson correlation coefficient, and statistical significance between groups was determined by using the Student t test.

Results: The 45 study patients included 27 men and 18 women (age range, 19-71 years; average age, 55.8 years). The SHAPE gradient between the portal and hepatic veins was in good overall agreement with the hepatic venous pressure gradient (HVPG) (R = 0.82). Patients at increased risk for variceal hemorrhage (HVPG ≥ 12 mm Hg) had a significantly higher mean subharmonic gradient than patients with lower HVPGs (1.93 dB ± 0.61 [standard deviation] vs -1.47 dB ± 0.29, P < .001), with a sensitivity of 100% and a specificity of 81%, indicating that SHAPE may be a useful tool for the diagnosis of clinically important portal hypertension.

Conclusion: Preliminary results show SHAPE to be an accurate noninvasive technique for estimating portal hypertension.

Figures

Figure 1:

Flowchart of enrollment procedures in this pilot study. Values are numbers of patients.

Figure 2a:

(a) US image in 56-year-old man with ascites shows the dual-imaging display mode, with the subharmonic ROI (yellow box) placed within the portal vein (PV) for acoustic output calibration. The hepatic vein (HV), the portal vein, and the inferior vena cava (IVC) are marked. (b) Graph shows subharmonic amplitudes as a function of acoustic output power. Red dot = selected acoustic output after optimization, where the change in subharmonic amplitude is greatest (as determined by the automatic power control program).

Figure 2b:

(a) US image in 56-year-old man with ascites shows the dual-imaging display mode, with the subharmonic ROI (yellow box) placed within the portal vein (PV) for acoustic output calibration. The hepatic vein (HV), the portal vein, and the inferior vena cava (IVC) are marked. (b) Graph shows subharmonic amplitudes as a function of acoustic output power. Red dot = selected acoustic output after optimization, where the change in subharmonic amplitude is greatest (as determined by the automatic power control program).

Figure 3a:

SHAPE acquisitions (obtained at their respective optimal acoustic outputs) in two patients. (a) Image in 56-year-old man with an HVPG of 5 mm Hg insonated at an acoustic output of 10%. (This patient had a fibrosis score of 2, a hemoglobin level of 9.4 g/dL [94 g/L], a platelet count of 327 × 109/L, an albumin level of 2.7 g/dL [27 g/L], a creatinine level of 4.8 mg/dL [424.32 μmol/L], a bilirubin level of 0.2 mg/dL [3.42 μmol/L], and an international normalized ratio of 1.27 seconds.) Strong subharmonic signal in the portal vein (PV) is seen within the color box, while very limited signal is observed within the hepatic vein (HV). (b) Image in 60-year-old woman with an HVPG of 23 mm Hg insonated at an acoustic output of 70%. (This patient had a fibrosis score of 4, a hemoglobin level of 10.9 g/dL [109 g/L], a platelet count of 219 × 109/L, an albumin level of 2.6 g/dL [26 g/L], a creatinine level of 1.1 mg/dL [97.24 μmol/L], a bilirubin level of 7.4 mg/dL [126.54 μmol/L], and an international normalized ratio of 1.61 second.) In this patient, subharmonic signals are greater in the hepatic vein (HV) than in the portal vein (PV). In patients like this one with elevated HVPGs, hydrostatic pressure suppresses the subharmonic signal within the portal vein, lowering its signal intensity relative to the signal intensity of the hepatic vein.

Figure 3b:

SHAPE acquisitions (obtained at their respective optimal acoustic outputs) in two patients. (a) Image in 56-year-old man with an HVPG of 5 mm Hg insonated at an acoustic output of 10%. (This patient had a fibrosis score of 2, a hemoglobin level of 9.4 g/dL [94 g/L], a platelet count of 327 × 109/L, an albumin level of 2.7 g/dL [27 g/L], a creatinine level of 4.8 mg/dL [424.32 μmol/L], a bilirubin level of 0.2 mg/dL [3.42 μmol/L], and an international normalized ratio of 1.27 seconds.) Strong subharmonic signal in the portal vein (PV) is seen within the color box, while very limited signal is observed within the hepatic vein (HV). (b) Image in 60-year-old woman with an HVPG of 23 mm Hg insonated at an acoustic output of 70%. (This patient had a fibrosis score of 4, a hemoglobin level of 10.9 g/dL [109 g/L], a platelet count of 219 × 109/L, an albumin level of 2.6 g/dL [26 g/L], a creatinine level of 1.1 mg/dL [97.24 μmol/L], a bilirubin level of 7.4 mg/dL [126.54 μmol/L], and an international normalized ratio of 1.61 second.) In this patient, subharmonic signals are greater in the hepatic vein (HV) than in the portal vein (PV). In patients like this one with elevated HVPGs, hydrostatic pressure suppresses the subharmonic signal within the portal vein, lowering its signal intensity relative to the signal intensity of the hepatic vein.

Figure 4a:

(a) Box plot shows the subharmonic gradient—the average subharmonic amplitude in the hepatic vein (HV) minus that in the portal vein (PV)—in patients at risk for variceal bleeding (HVPG ≥ 12 mm Hg) and in those at lower risk (HVPG < 12 mm Hg). (b) The ROC curves demonstrate the ability to use SHAPE to identify patients with portal hypertension (HVPG ≥ 10 mm Hg) and those at risk for variceal bleeding (HVPG ≥ 12 mm Hg). Az = area under the ROC curve.

Figure 4b:

(a) Box plot shows the subharmonic gradient—the average subharmonic amplitude in the hepatic vein (HV) minus that in the portal vein (PV)—in patients at risk for variceal bleeding (HVPG ≥ 12 mm Hg) and in those at lower risk (HVPG < 12 mm Hg). (b) The ROC curves demonstrate the ability to use SHAPE to identify patients with portal hypertension (HVPG ≥ 10 mm Hg) and those at risk for variceal bleeding (HVPG ≥ 12 mm Hg). Az = area under the ROC curve.

Figure 5a:

(a) Graph shows correlation between the noninvasively determined subharmonic gradient—the average subharmonic amplitude in the hepatic vein (HV) minus that in the portal vein (PV)—and the corresponding HVPG, which is measured by using a pressure catheter during biopsy. (b) Graph shows correlation between the subharmonic gradient and the corresponding HVPG measured in patients at higher risk of variceal bleeding (HVPG ≥ 12 mm Hg).

Figure 5b:

(a) Graph shows correlation between the noninvasively determined subharmonic gradient—the average subharmonic amplitude in the hepatic vein (HV) minus that in the portal vein (PV)—and the corresponding HVPG, which is measured by using a pressure catheter during biopsy. (b) Graph shows correlation between the subharmonic gradient and the corresponding HVPG measured in patients at higher risk of variceal bleeding (HVPG ≥ 12 mm Hg).