Liver microbubble transit time compared with histology and Child-Pugh score in diffuse liver disease: a cross sectional study

Abstract

Background: A previous pilot study showed that early arrival time of a microbubble in a hepatic vein is a sensitive indicator of cirrhosis.

Aim: To see if this index can also grade diffuse liver disease.

Patients: Thirty nine fasted patients with histologically characterised disease were studied prospectively. Nine patients had no evidence of liver fibrosis, 10 had fibrosis without cirrhosis, and 20 had cirrhosis (five Child's A, seven Child's B, and eight Child's C).

Methods: Bolus injections of a microbubble (Levovist; Schering, Berlin) were given intravenously, followed by a saline flush. Time intensity curves of hepatic vein and carotid artery spectral Doppler signals were analysed. Hepatic vein transit time (HVTT) was calculated as the time after injection at which a sustained signal increase >10% of baseline was seen. Carotid delay time (CDT) was calculated as the difference between carotid and hepatic vein enhancement.

Results: Diagnostic studies were achieved in 38/39 subjects. Both HVTT and CDT became consistently shorter with worsening disease, as follows (means (SD)): HVTT: no fibrosis 44 (25) s, fibrosis 26 (8) s, Child's A 21 (1) s, Child's B 16 (3) s, and Child's C 16 (2) s; CDT: no fibrosis 31 (29) s, fibrosis 14 (6) s, Child's A 8 (1) s, Child's B 4 (4) s, and Child's C 3 (3) s. These differences were highly significant (p<0.001, ANOVA comparison). A HVTT <24 s and a CDT <10 s were 100% sensitive for cirrhosis (20/20 and 18/18, respectively) but not completely specific: 2/8 subjects with fibrosis had CDT values <10 s and 3/9 had HVTT <24 s.

Conclusion: This minimally invasive test shows promise not only in diagnosing cirrhosis but also in assessing disease severity.

Figure 1

Illustration of the method used. A bolus injection of a microbubble was given into an antecubital fossa vein and simultaneous time intensity profiles were performed using Doppler ultrasound of the hepatic vein and carotid artery. CW, continuous wave; A/D, analogue to digital.

Figure 2

A typical example of a spectral Doppler trace before (A) and after (B) injection of the microbubble. Note that the signal became stronger. It is the change in intensity of the signal with time that is analysed.

Figure 3

An example of hepatic venous (A) and carotid (B) time intensity profiles in a subject with cirrhosis (Child’s C). A plot of Doppler intensity (proportional to relative microbubble concentration) against time after injection in seconds is shown. The raw (thin line) and smoothed (thick line) data are shown. The broken line shows that baseline intensity increased by 10% and arrival times can be read graphically as the point where the signal increases above this level (see text). The arrival time of the microbubble bolus is 18 s in the carotid artery and 20 s in the hepatic vein (HVTT), giving a carotid delay time (CDT) of 2 s.

Figure 4

An example of hepatic venous (A) and carotid (B) time intensity profiles in a subject with mild hepatitis using the same notation as in fig 3 ▶. The injection was given after a baseline of 20 s. The arrival time of the microbubble bolus is therefore 19 s in the carotid artery and 42 s in the hepatic vein (HVTT), giving a difference (carotid delay time (CDT)) of 23 s.

Figure 5

Minimal hepatic vein transit time (HVTT) plotted against diagnosis as a scatterplot, with mean values indicated as a horizontal line.

Figure 6

Minimal carotid delay time (CDT) plotted against diagnosis as a scatterplot, with mean values indicated as a horizontal line.

Figure 7

Limits of agreement plot of hepatic vein transit time where two good quality traces were obtained in the same subject. Two lines have been added to each plot showing the mean difference plus or minus 1.96 SD values.

Figure 8

Limits of agreement plot of carotid delay time where two good quality traces were obtained in the same subject. Two lines have been added to each plot showing the mean difference plus or minus 1.96 SD values.