Contrast-enhanced ultrasonography for the evaluation of liver fibrosis after biliary obstruction

AIM:To investigate perfusion change in contrastenhanced ultrasonography(CEUS) to evaluate liver fibrosis based on biliary obstruction using an animal model.METHODS:New Zealand white rabbits(3-4 kg) underwent bile duct ligation to form a biliary obstruction model.We performed liver CEUS and laboratory tests on the day before the operation(day 0) and every 7 postoperative days until the rabbits were sacrificed.After CEUS,signal intensity of liver parenchyma with a time-intensity curve was analyzed.Perfusion parameters were automatically calculated from regionof-interests,including peak signal intensity,mean transit time,area under the curve and time to peak.Histological grades of liver fibrosis were assessed according to the Metavir score system immediately after sacrifice.Generalized estimating equations were used to analyze the association between liver fibrosis grades and perfusion parameters for statistical analysis.The perfusion parameters were measured on the last day and the difference between day 0 and the last day were evaluated.RESULTS:From the nine rabbits,histological grades of liver fibrosis were grade 1 in one rabbit,grade 2 and 3 in three rabbits each,and grade 4 in two rabbits.Among the four CEUS parameters,only the peak signal intensity measured on the last day demonstrated a significant association with liver fibrosis grades(OR =1.392,95%CI:1.114-1.741,P =0.004).The difference in peak signal intensity between day 0 and the last dayalso demonstrated an association with liver fibrosis(OR =1.191,95%CI:0.999-1.419,P =0.051).The other parameters tested,including mean transit time,area under the curve,and time to peak,showed no significant correlation with liver fibrosis grades.CONCLUSION:This animal study demonstrates that CEUS can be used to evaluate liver fibrosis from biliary obstruction using peak signal intensity as a parameter.

D-galactosamine based canine acute liver failure model

Background: Appropriate preclinical evaluation of a bioartificial liver assist device (BAL) demands a large animal model, as presented here, that demon- strates many of the clinical features of acute liver failure and that is suitable for clinical qualitative and quantitative evaluation of the BAL. A lethal canine liver failure model of acute hepatic failure that re- moves many of the artifacts evidenced in prior canine models is presented. Methods: Six male hounds, 24-30 kg, under isoflu- rane anesthesia, were administered 1.5 g/kg D- galactosamine intravenously. Canine supportive care followed a well-defined management protocol that was guided by electrolyte and invasive monitoring consisting of arterial pressure, central venous pres- sure, extradural intracranial pressure (ICP), pul- monary artery pressure, and end-tidal CO_2. The animals were treated until death-equivalent, defined as inability to sustain systolic blood pressure>80 mmHg for 20 minutes despite maximal fluids and 20 μg·kg^(-1)·min^(-1) dopamine infusion. Results: The mean survival time was 43.7±4.6 hours (mean±SE). All animals showed evidence of progressive liver failure characterized by increasing liver enzymes (aspartate transaminase from 26 to 5977 IU/L; alanine transaminase from 32 to 9740 IU/L), bilirubin (0.25 to 1.30 mg/dl), ammonia (19. 8 to 85. 3 μmol/L), and coagulopathy (pro- thrombin time from 8.7 to 46 s). Increased lability and elevations in intracranial pressures were ob- served. All animals were refractory to maintenance of cerebral perfusion pressure even with only mode- rately elevated intracranial pressure. Severe neuro- logic obtundation, seen in 2 of 6 animals, was associ- ated with elevations of ICP above 50 mmHg. Post- mortem liver histology showed evidence of massive hepatic necrosis. Postmortem blood and ascites mi- crobial growth was consistent with possible transloca- tion of intestinal microbes. Conclusions: The improved lethal canine liver failure model presented here reproduces many of the clinical features of acute liver failure. The model may prove useful for qualitative and quantitative evaluation of BALs.