Hepatic vein transit times using a microbubble agent can predict disease severity non-invasively in patients with hepatitis C

• Published in: Gut Vol. 54; no. 1; pp. 128 - 133
• Main Authors: Lim, A K P, Taylor-Robinson, S D, Patel, N, Eckersley, R J, Goldin, R D, Hamilton, G, Foster, G R, Thomas, H C, Cosgrove, D O, Blomley, M J K
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Society of Gastroenterology 01.01.2005; BMJ; BMJ Publishing Group LTD; Copyright 2005 by Gut
• Subjects: Adult; Aged; alanine aminotransferase; ALT; APRI; aspartate aminotransferase; AST; Biological and medical sciences; Biopsy; Blood Flow Velocity; Carotid arteries; carotid delay time; CDT; Contrast Media; Epidemiologic Methods; Female; fibrosis; functional studies; Genotype & phenotype; HCV; hepatic vein transit time; Hepatic Veins - diagnostic imaging; Hepatic Veins - physiopathology; Hepatitis; hepatitis C; Hepatitis C virus; Hepatitis C, Chronic - diagnostic imaging; Hepatitis C, Chronic - pathology; Hepatitis C, Chronic - physiopathology; Hospitals; Human viral diseases; Humans; HVTT; Infectious diseases; Liver; Liver cirrhosis; Liver diseases; Male; Medical sciences; Microbubbles; Middle Aged; Mortality; necroinflammatory; PCR; polymerase chain reaction; Polysaccharides; R&D; ratio of serum AST/platelet count; Research & development; Studies; tracer studies; Ultrasonic imaging; Ultrasonography, Doppler - methods; ultrasound; Veins & arteries; Viral diseases; Viral diseases of the digestive system; Viral hepatitis; Germany; Infection; Human; Transit time; Hepatic vein; Viral disease; Digestive diseases; Hepatic disease; Predictive factor; Viral hepatitis C
• ISSN: 0017-5749; 1468-3288; 1458-3288
• DOI: 10.1136/gut.2003.030965

Background and aims: A reliable non-invasive assessment of the severity of diffuse liver disease is much needed. We investigated the utility of hepatic vein transit times (HVTT) for grading and staging diffuse liver disease in a cohort of patients with hepatitis C virus (HCV) infection using an ultrasound microbubble contrast agent as a tracer. Materials and methods: Eighty five untreated patients with biopsy proven HCV induced liver disease were studied prospectively. All were HCV RNA positive on polymerase chain reaction testing. Based on their histological fibrosis (F) and necroinflammatory (NI) scores, untreated patients were divided into mild hepatitis (F ⩽2/6, NI ⩽3/18), moderate/severe hepatitis (3 ⩽F <6 or NI ⩾4), and cirrhosis (F = 6/6) groups. In addition, 20 age matched healthy volunteers were studied. After an overnight fast, a bolus of contrast agent (Levovist) was injected into an antecubital vein and spectral Doppler signals were recorded from both the right and middle hepatic veins for analysis. HVTTs were calculated as the time from injection to a sustained rise in Doppler signal >10% above baseline. The Doppler signals from the carotid artery were also measured in 60 patients and carotid delay times (CDT) calculated as the difference between carotid and hepatic vein arrival times. The earliest HVTT in each patient was used for analysis. Results: Mean (SEM) HVTT for the control, mild hepatitis, moderate/severe hepatitis, and cirrhosis groups showed a monotonic decrease of 38.1 (2.8), 38.8 (2.4), 26.0 (2.4), and 15.8 (0.8) seconds, respectively. Mean (SEM) CDT for the control, mild hepatitis, moderate/severe hepatitis, and cirrhosis patients again showed progressive shortening of 30.3 (2.6), 25.9 (2.6), 14.8 (2.1), and 5.6 (1.2) seconds, respectively. There were significant differences between the groups for HVTT (ANOVA, p<0.001) and CDT (ANOVA, p<0.001). There was 100% sensitivity and 80% specificity for diagnosing cirrhosis and 95% sensitivity and 86% specificity for differentiating mild hepatitis from more severe liver disease. Conclusion: We have shown, for the first time, that HVTT using an ultrasound microbubble contrast agent can assess HCV related liver disease with clear differentiation between mild hepatitis and cirrhosis. There were significant differences between these two groups and the moderate/severe hepatitis group. CDT offers no additional benefit or greater differentiation than HVTT and can be omitted, thus simplifying this technique. HVTT may complement liver biopsy and may also be a useful alternative for assessment of liver disease in patients who have contraindications to biopsy.