The Experimental And Clinical Study Of Ultrasonographic Evaluation On Hepatic Fibrosis Rabbits And Patients With Portal Hypertension

Ultrasonography and its related technology made it possible that the early diagnose of liver fibrosis and evaluation of portal hypertension based on the non-invasiveness and convenience. It will help greatly to the investigation on prevent cirrhotic process or reverse the process of hepatic fibrosis and the comprehemsive evaluation on hemodynamic changes in patients with portal hypertension.Purpose:1) To discuss the indicative significance of ultrasound contrast agent on liver fibrosis stage according to the perfusion dynamics of a self-made contrast agent;2) The objective of this study was to investigate the relationship between a series of portal hemodynamic parameters obtained using Doppler ultrasonography and portal pressure measured directly from patients with portal hypertension (PHT). We aimed to identify which parameter and to what degree these parameters were suitable to assess the severity of PHT. Material and method: 1) Experimental hepatic fibrosis models of 35 adult healthy New Zealand rabbits were induced via administration of CCL4 (0.01ml/kg BW) every 3 days for 3 months. The liver of rabbit were obtained at 0th day, 30th day, 40h day, 60th day and 90th day, then fixed by 10% formaldehyde and stained by hematoxylin eosin (HE) and Masson three colors, then scored from F0 stage to F4 stage;2) The intrahepatic circulatory time of the contrast agent was analyzed via an image and Cine-loop display. Calculations of the perfusion-related parameters including the peak signal intensity (PSI) and peak signal intensity time (PIT) of the portal vein and parenchyma were obtained from an analysis of the time-acoustic intensity curve;3) Patients who had been clinically diagnosed with PHT and accepted surgical therapy, were investigated. Twenty-five healthy volunteers without history of chronic liver disease were enrolled as the controls;4) Portal pressure was measured directly through the right gastroepiploic vein. Liver biopsies were obtained during operation under the guidance of ultrasound. Morphologic changes of the liver and ascites were determined during the operation.5) Doppler ultrasonographic examinations were conducted with Sequire 512 and a 3.5 MHz phased array transducer. All patients were examined the day before operation and control subjects fasted overnight before investigated;6) The investigated subjests include portal vein, hepatic artery, hepatic vein and splenic artery. The measured parameters include the mean portal vein velocity, hepatic artery resistive index, hepatic artery pulsatility index, splenic artery resistive index and splenic artery pulsatility index. The calculated indexes include portal vein blood flow, congestion index, hepatic vascular index, hepatic artery buffer index and portal hypertension index.7) All the parameters were compared using an analysis of variance (ANOVA). Linear regression analysis was used to assess the correlation between all parameters in fast and portal pressure.Results:1) We had established 12 F0 and F1 stage models; 9 F2 stage models; 8 F3 stage models and 6 F4 stage models. The reasons of death are gastroenteric haemorrhagic necrosis to CCL4 and haemorrhage from the liver biopsy. The success rate of animal model construction is 50%2) Hepatic artery to vein transmit time (HA-HVTT) was significantly shorter at F4 stage (mean 2.95s) compared with those in other stages, p<0.01). The average PSI difference of PV-parenchyma was 13.62 dB in F4 stage, significantly differed between F4 stage and other early stages (p<0.01).3) Fifty-seven qualified for surgical portosystemic shunts therapy and were included in our study. The free portal pressure is 30.09±4.151mmHg;4) Hepatic vein waveform took on II type in patients with portal hypertension had higher portal pressure;5) HAPI, SpAPI, CI and PHI in portal hypertention group were significantly higher than control group (1.615±0.453, 1.088±0.179, 0.127±0.067, 2.093±0.506, p<0.05). HBI and LVI in portal hypertention group were significantly lower than control group (1.389±1.813, 10.308±3.260, p<0.05). There were no significant difference between two groups of PVVel, HARI and SpRI. 6) HAPI with 1.34 was suitable for the diagnosis of portal hypertension with sensitivity was 73%, the specificity was 80% and the accuracy was 74%. LVI with 11.3 cm/s was suitable for the diagnosis of portal hypertension with sensitivity was 63%, the specificity was 78% and the accuracy was 66%. That PHI was higher than 1.4 m/s-1 indicated existence of portal hypertension with sensitivity was 80%, the specificity was 69%.7) Three other indexes had significant linear correlations with portal pressure: HARI (r=0.699, p<0.001), HAPI (r=0.582, p<0.001), LVI (r=-0.501, p=0.003). Contrary to the other indexes, LVI was inversely related with portal pressure. The Child-Pugh score showed a significant correlation with portal pressure (r=0.589, p=0.044).Conclusion:1) HA-HVTT and the PSI difference of the microbubble perfusion in liver parenchyma and PV were considered to reflect the degree of hepatic fibrosis;2) Intrahepatic vascular resistance increased in patients with portal hypertension. HAPI and HARI increased with portal pressure increased;3) The baseline and acute hepatic artery buffer capability weakened in patients with portal hypertension. However, with the portal pressure increased, the acute hepatic artery buffer capability then was activated;4) The portalization of hepatic venous waveform indicated higher portal pressure.