correlating with increased severity of liver disease, on account of circulatory changes, including arterialisation of the hepatic sinusoidal bed, intra- and extrahepatic shunting and the hyperdynamic circulation present with cirrhosis (see figure 2). In a cohort of 85 patients with CHC assessed by HVTT, there was 100% sensitivity and 80% specificity for cirrhosis, and 95% sensitivity and 86% specificity for differentiation of mild hepatitis from more severe liver disease. The ability of microbubbles to stratify mild and moderate disease suggests that mechanisms other than those directly related to portal hypertension may contribute to effects seen.
Hence, liver stiffness cannot, as originally assumed, be considered a measure of hepatic fibrosis alone, but the net result of a number of biological processes of which fibrosis is one. Interpretation of results should therefore be made in the context of the individual clinical scenario and corroborated by other non-invasive marker modalities.
USE OF ULTRASOUND CONTRAST AGENTS Microbubble contrast agents are small, stabilised gas-filled phospholipid bubbles (about 3mm) that resonate when subject to
Figure 3: 31
ultrasound, amplifying the reflected signal, thus enhancing intravascular signal for several minutes after intravenous injection and increasing signal from vessels and tissues. Safety and tolerance with current agents is excellent. When quantified, the resultant signal intensity change is proportional to microbubble concentration. A simple microbubble-enhanced
ultrasound test to measure hepatic vascular transit times (HVTT) by timing the arrival of contrast agent in the hepatic artery and then the hepatic vein has been developed. A curve of signal intensity against time can be plotted, with shorter arrival times
P MRS. PME/PDE ratios obtained from in vivo hepatic 31P MRS varying with
severity of hepatitis C-associated liver disease. Adapted from Lim et al. 2003. .5
MAGNETIC RESONANCE TECHNIQUES Both MR imaging (MRI) and MR spectroscopy (MRS) techniques have been applied to assess the severity of chronic liver diseases. MRI techniques include dynamic superparamagnetic iron oxide and gadolinium enhanced studies, which have been shown to demonstrate reticular- nodular patterns, thought to represent septal hepatic fibrosis, allowing the qualitative discrimination of moderate to severe, from mild fibrosis. Objective stratification of fibrosis severity in patients with chronic hepatitis C has been reported using diffusion-weighted MR imaging. Furthermore, magnetic resonance elastography, which, like transient elastography measures liver stiffness, allows visualisation of a map of hepatic liver stiffness. MRS examines the chemico-physical environment of nuclei in a region of interest, providing metabolic information in the form of a spectrum, of relevance in chronic liver disease.
.4
MAGNETIC RESONANCE SPECTROSCOPY In vivo 31
P MRS is a safe, reproducible
technique, which provides biochemical information on hepatic metabolic processes. Typical in vivo 31
P MR liver .3 .2 .1 N = 15 Control 18 Mild 19 Moderate Severity of disease 60
www.lifesciencesmagazines.com 11 Cirrhosis
spectra contain phosphomonoester (PME), phosphodiester (PDE), inorganic phosphate (Pi) and ATP resonances, reflecting cellular energy state, intermediates of carbohydrate metabolism, precursors of cell membrane synthesis and breakdown. These resonances are multicomponent, but more detailed biochemical information may be obtained with in vitro MRS at higher magnetic field strengths (11.7T -14.0T) than in clinical studies (1.5T - 3.0T).
Mean (PME/PDE) +/- 2S.E.
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