Hepatic arterial doppler sonography in patients with cirrhosis and controls: observer and equipment variability with use of the ultrasonic contrast agent SHU 508A.

PURPOSE: The aims of this study on hepatic arterial Doppler sonography were to ascertain interobserver and interequipment variability, to investigate any potential artificial influence of the ultrasonic contrast agent on the Doppler measurements and to compare the results in healthy and cirrhotic subjects. METHODS: Doppler sonography of the left hepatic artery was performed in nine healthy and nine cirrhotic subjects by three independent observers using three different devices. Continuous infusion of the ultrasonic contrast agent SHU 508A and placebo were administered in a double blind fashion. Systolic, mean and end diastolic peak velocities as well as resistive and pulsatility indices were measured. RESULTS: Equipment associated variances (5.8 - 12.7 %) of the five Doppler parameters were greater than interobserver variances (0.3 - 3.6 %). No significant differences were observed between the velocities using ultrasonic contrast agent and placebo. Systolic (65.9 +/- 3.6 vs. 47.7 +/- 4.2 cm/s mean +/- SE, p = 0.02) and mean peak velocity (35.4 +/- 1.6 vs. 24.5 +/- 1.8 cm/s, p = 0.007) were significantly higher in cirrhotic than in healthy subjects whereas the resistive and pulsatility indices were not different. CONCLUSIONS: Doppler sonography of the left hepatic artery performed by various observers is reproducible as long as the same device is used. Under clinical conditions, velocities are correctly measured with the use of ultrasonic contrast agent and are elevated in patients with cirrhosis.

13C-Methacetin metabolism in patients with cirrhosis: relation to disease severity, haemoglobin content and oxygen supply.

BACKGROUND: Hypoxia may contribute to impairment of liver function and thus interfere with results of liver tests. In patients with cirrhosis, cytochrome P-450 mediated metabolism of substrates is facilitated in the presence of supplemental oxygen. It has not been studied how this relates to liver function and haemoglobin content. AIM: We questioned how oxygen supplementation would influence the hepatic microsomal function as assessed by the 13C-methacetin breath test in patients with cirrhosis of different severity and different degrees of anaemia. METHODS: 13C/12C ratios in exhaled breath assessed by non-dispersive infrared spectrometry were studied in 34 patients with cirrhosis (Child A/B/C 9/17/8) after administration of 75 mg 13C-methacetin p.o. with and without oxygen inhalation (4 L/min). RESULTS: In patients breathing room air the total amount of 13C exhaled weakly correlated both with the Child-Pugh score (r = - 0.41, P < 0.02) and haemoglobin concentrations (r = 0.46; p = 0.006). Oxygen supplementation increased the total amount of 13C exhaled by 68 +/- 90% (P < 0.001). This effect was similar in Child-Pugh classes A (43 +/- 55%), B (83 +/- 80%) and C (66 +/- 123%) and not related to the Child-Pugh score. CONCLUSIONS: Our results suggest that tests of microsomal liver function are independently influenced both by oxygen delivery and the Child-Pugh score.

Hepatic arterial blood flow velocities: assessment by transcutaneous and intravascular Doppler sonography.

BACKGROUND/AIMS: Doppler sonography has been used to assess hepatic arterial perfusion in a number of published reports. However, adequate validation studies are available for neither the transcutaneous nor the intravascular Doppler approach. The aim of this comparative study was to assess hepatic arterial perfusion with both methods. METHODS: In 15 patients the right hepatic artery was examined with intravascular and transcutaneous Doppler sonography after calibration of Doppler devices in vitro with a thread model. The measurements were performed simultaneously in five and separately within 24 h in 10 patients. RESULTS: In vitro, the correlations between the velocities of the thread and the velocities as determined by intravascular (r=1.0, p<0.001) and transcutaneous Doppler sonography (r=1.0, p<0.001) were excellent. In vivo, the best correlation was found for systolic peak velocities (intravascular: 58.5+/-18.1 cm/s, mean+/-standard deviation, transcutaneous: 58.2+/-25.2 cm/s, r=0.63, p=0.01). Although lower mean (intravascular: 26.5+/-7.7 cm/s, transcutaneous: 32.5+/-14.4 cm/s) and end-diastolic velocities (intravascular: 11.5+/-4.0 cm/s, transcutaneous: 18.4+/-8.6 cm/s) were found with intravascular compared to transcutaneous Doppler sonography, significant correlations were demonstrable between results obtained by both methods (r=0.63, p=0.01 for mean and r=0.57, p=0.025 for diastolic velocities). Similarly, the calculated resistive (intravascular: 0.79+/-0.07, transcutaneous: 0.68+/-0.06, r=0.65, p=0.009) and pulsatility indices (intravascular: 1.78+/-0.47, transcutaneous: 1.26+/-0.25, r=0.55, p=0.034) were somewhat higher using the intravascular device, but correlated well with the numbers obtained by the transcutaneous approach. CONCLUSIONS: The data suggest that with use of different Doppler devices, systolic velocities are the most suitable parameter for Doppler assessment of hepatic arterial perfusion.

Hepatic arterial flow volume and reserve in patients with cirrhosis: use of intra-arterial Doppler and adenosine infusion.

BACKGROUND & AIMS: In cirrhosis, liver blood flow becomes increasingly dependent on the hepatic artery. The aim of this study was to investigate hepatic arterial blood flow volume and resistance and hepatic arterial flow reserve in relation to liver function and systemic hemodynamic alterations in patients with cirrhosis. METHODS: In 38 patients with cirrhosis, liver function, cardiac output, and systemic vascular resistance were studied, and hepatic arterial blood flow velocity, flow volume, and pulsatility index at baseline and during intra-arterial administration of adenosine (2-40 microg. min-1. kg body wt-1) were assessed by angiography combined with intravascular Doppler flowmetry. RESULTS: Hepatic arterial flow velocity was 21 +/- 11, 31 +/- 17, and 41 +/- 27 cm/s; flow volume was 266 +/- 246, 342 +/- 289, and 417 +/- 220 mL/min; and pulsatility index was 2.2 +/- 0.7, 1.7 +/- 0.6, and 1.5 +/- 0.5 in Child-Pugh classes A, B, and C, respectively (differences not statistically significant). Adenosine-induced changes in these parameters were more marked in Child-Pugh class A (68 +/- 15 cm/s, 1246 +/- 486 mL/min, and -1.14 +/- 0.5) than in class C (45 +/- 23, P < 0.05; 704 +/- 492, P = 0.02; and -0.58 +/- 0.38, P < 0.05). Using analysis of variance, cardiac index, systemic vascular resistance, and ascites, but not Child-Pugh class, were related to baseline values and adenosine-induced changes. CONCLUSIONS: Adenosine is a potent dilator of the hepatic artery in humans. The data suggest that hepatic arterial blood flow and adenosine-dependent flow reserve in patients with cirrhosis are under systemic hemodynamic or neurohormonal control.

Effects of cyclosporine A on the rat liver and kidney protein pattern, and the influence of vitamin E and C coadministration.

The effects of cyclosporine A (CsA), a potent immunosuppressive drug, were examined in rat liver and kidney samples using two-dimensional electrophoretic protein analysis. Of a total of 370 liver and 336 kidney spots analyzed, 8% (29 spots) and 6% (19 spots), respectively, showed a significant drug-induced change (p < 0.01), which was predominantly reflected in increased protein abundance (62% and 74% of the changes, respectively). Of the 48 proteins changed in either organ, 14 were most probably common to both tissues and one of these was significantly increased in both the liver and the kidney. Most of the other 13 showed similar trends (either increases or decreases) in both organs. However, the most striking drug effect seen in this study concerned an unidentified protein present only in the kidney, which completely disappeared upon CsA treatment. It was also investigated whether the drug-induced changes could be prevented by the coadministration of the radical scavengers vitamin E and C with CsA. Spots changed by the administration of the drug were classified according to three different categories, based on their response profiles in rats treated with CsA in combination with the vitamins: (i) spots which were changed by CsA as well as by CsA in combination with the vitamins (12 liver and 4 kidney spots), (ii) spots which were changed by CsA and showed an additional increase of this change by CsA plus the vitamins (no liver and 4 kidney spots), and (iii) spots which were changed by CsA but not by CsA in combination with the vitamins (8 liver and 6 kidney spots). These results showed that in both organs the vitamins were able to prevent around 30% of the effects caused by CsA, and that two-dimensional gel electrophoresis is an excellent tool to demonstrate such drug interactions at the molecular level.