| Objective:To establish a model for small pig's end-stage liver disease, by 16-sectioned spiral CT was used to study the changes of the hepatic volume,density, portal vein pressure and the axiom for the liver's haemodynamics, and make a cross-check analysis by the pathology,blood biochemical indexs,and the indocyanine green R151ICG,to obtain the best morphology and functional evaluation indexs of the end-stage liver diseases. Then calculus formula for the correlation of free portal venous pressure with priming volume and diagnosed hepatic end-stage liver disease with MSCTP.Materials and Methods:The subjects, supplied by the Animal Experiment Centre of Guangxi Medical University, were 40 Bama small pigs of the same germline, who were divided at random into a experiment group of 40 and a control group of 20, male or female, aged 4 months, weighing 15-20 kg. In the experiment, the establishment of the end-stage liver disease model and the study with 16-slices spiral CT perfusion imaging were conducted simultaneously. Composite factors were employed to establish a model (a mixed feed of 65%of corn meal+35%of Cholest+CC14+PBS, with 10%absolute alcohol as the only one potion) for the experiment group, semel in die,24 weeks successively, and the normal feeding (65%of corn meal+35%of rice bran, with clear water as the only one potion), was synchronically given to the controlled. The two groups of the animal received 16-slices spiral CT perfusion scanning, haemospasia for the biochemical indicators of hepatic function (incl.T. BIL, Alb, Glb, A/G, ALT, AST, Cr,PT,INR), laparotomy for measuring portal venous free pressure and CT-aiming aspiration biopsy.After the routine CT scaning,the density of the liver,spleen,and the liver/spleen, the caliber of the MVP and its main branch were calculus,respectively.And the volume of the liver were measured by the CT automaticly. The perfusion data received image-analysis with functional software(Body perfect-syngo CT2009A) in the machine. CT(Hu) was determined respectively in the regions of interest of the aorta, portal vein, spleen and liver to acquire relative time density curve(TDC), i.e. correspondingly the density increase value from plain-scanning the regions of interest. A round or elliptic region of interest was taken in the aorta and portal vein, and the regions of interest in the liver and spleen were drawn along the organs'borderlines. The region of interest in the liver included mainly bulk of hepatic lobes at the scanned deck, with the liver's great vessels out of the way; the ROI of the spleen, the whole at the deck, was taken, some 1cm away from the organ's borderline to avoid the volume effect. The software, with TDC produced automatically by it, calculated with the maximum slope rate method to produce automatically perfusion parameters:hepatic artery perfusion (HAP), portal venous perfusion (PVP), total hepatic blood flow (THBF) and hepatic artery perfusion index (HPI), of which THBF= HAP+PVP. Each metered index was measured repeatedly twice, with the mean value taken.The standard of the study group of end-stage liver disease were(1) Typical example of cirrhosis in pathology.(2) Abdominal dropsy.(3) Biochemical indicator including T.BIL>30.9±11.9umol/L, ALB＜37.96±3.96 g/L, Cr>80.10±16.23umol/L, PT> 13.21±3.43s.And the Child-Pugh (CTP), Modle of end-stage liver diease (MELD) were calculus.The CTP were dividing into three group A,B,and C.The MELD were dividing into three groups,which was< 15, 15～4,≥25 respectivly. All the data obtained were analyzed statistically with SPSS15.0 software, the outcome of which were demonstrated through mean±standard deviation. The comparison of the multiple-grouped mean applied One-way ANOVA, and non-parameter rank sum test (Kruskal-Wallis test) for heterogeneity of variance, with P<0.05 statistically different; the logistic regression analysis was used to study the CT morphology indicators and the CT perfusion parameters to study the influence of the mini-pig end-stage liver disease function reservation, with P<0.05 statistically different;.The receiver operating characteristic curve(ROC) was used to study the cut point of the CT parameters in diagnosis the end-stage liver disease. Regression equation for the derivation of the portal venous pressures at stages of hepatic cirrhosis, with the results and the measured values given double var Pearson linear correlation analysis; detemined the case of pressure value induced with regression equation in 95%confidence interval, assessed the concidence of results tested by FPP and MSCTP respectively. Results:(1) The model of end-stage liver disease in mini-pigs were succeed produced. No death in the control group of 20, with their liver's histopathologically normal appearing until the 20th week; 16 deaths in the experiment group of 40 at the end of 24th week; Achievement rate for those models was 73.33%(44/60).the normal group was 80 cases,the slightly hepatic fibrosis was 82 cases,the early-stage liver cirrhosis was 62 cases,and the end-stage liver disease was 33cases. (2) Normal liver functional indexs:ALT (42.00±19.16) u/l, AST (27.26±9.51) u/l, ALB (37.96±3.96) g/1, GLO (19.74±9.12), A/G (1.12±0.05), T.BIL (30.9±11.9)umol/l, Cr (80.10±16.23) umol/L, PT (13.21±3.43s) s. ALT, AST, of the pathological models rose gradually, ALB decreased gradually and A/G ratio was inversion.All index in 0 grade in the normal control group and experimental group were not significant difference (p>0.05). The interclass ALT,AST,ALB,were statistically significant (p<0.05). (3) The liver volume in control group was (1166.18±181.35) cm3, and the liver volume in experimental group decreased gradually (1166.18±181.35cm3,1172.78±191.03 cm3,1075.89±198.29 cm3,850.53±141.04 cm3),which were statistically significant (p<0.05). (4) The liver density in control group was (63.43±5.34) HU, and the liver density in experimental group decreased gradually (63.43±5.34,59.52±4.99,55.11±4.57,53.33±5.44) HU, which were statistically significant (p<0.05).no statistically significant (p> 0.05) was founded in the density of the spleen in experimental group. (5)The MVP was gradually enlarger whith the pathological changes (1.39±0.27,1.37±0.05, 1.57±0.73,1.49±0.69) cm,from control group to experimental group.Which was the maximum of the main-branch of MVP in early-stage liver cirrhosis group (1.22±0.11,1.27±0.11) cm,but in the stage of end-stage liver disaese group,it becom shrin.The logistic regression analysis show that the standard coefficient of MVP was maximum(1.829),then was the right branch of MVP(1.315),the left branch of MVP(1.162).,which were statistically significant (p<0.01).(6) FPP in normal control group was (4.61±0.84) mmHg. in the control group to end-stage liver disease group,the FPP stepped up gradually and were respectively:(4.61±0.84,7.74±1.94,12.79±4.00,17.03±3.41)mmHg, with interclass statistical significance (p<0.05).All the indexs of 0 grade was not significant difference in normal control group and experimental group.(7) HAP of experimental first decreased and rose later, The average HAP in control group,slightly liver fibrosis group,early stage-liver cirrhosis group and end-stage liver disease group were 30.53±9.78,28.50±13.81,34.94±10.19, 41.08±9.76) ml/(100ml.min) respectively. PVP,LP decreased obviosly,from control group(109.46±22.49,140.00±29.74)ml/(100ml.min)to (56.32±20.92, 97.40±22.04) ml/(100ml.min)in end-stage liver disease group. HPI increased,to the end-stage liver disease group was (43.74±13.72)%. TTP prolong gradually,which were (124.33±21.49,134.48±26.76,149.76±28.88, 166.55±23.57)s from control group to the end-stage liver disease group.It was significant of the PVP and TLP in experimental group apt to decrease and had significant difference in all the group(P<0.05) HPI in experimental group increased and significant in all the group(P<0.05).(8)The indocyanine greenR15ICG were increased from control group to end-stage liver disease group (4.41±0.21,14.84±5.51,28.97±9.4,44.03±9.19)%, with interclass statistical significance (p<0.05).(9)The experimental group Child-Pugh A was 7cases, Child-Pugh B was 20cases, Child-Pugh C was 6cases;MELD<15 was cases,15-24was 15cases,≥25 was 9 cases,respectivly (10)The best correlationship between Child-Pugh, MELD score and R15ICG of the liver density, the caliber of the MVP,PVP,HPIwere founded,which r score were (-0.769,-0.667,-0.782), (-0.721,-0.731,-0.747), (+0.630,+0.634, +0.662), (+0.696,+0.744,+0.738),P<0.01,respectivly.(11)The logistic regression analysis show that the standardize regression coefficient of the HPI with the end-stage liver disease was (47.83, P<0.001),then the PVP,the voloum of the liver,TTP,TLP, the caliber of the MVP,HAP and the density of the liver,which were(-38.50,-30.36,21.17,19.6,17.34,11.56,8.43, P<0.01) respectivly.no significant difference in the spleen density and the liver/spleen ratio.Used the cut point of ROC,the HPI=43.92%to diagnosis the end-stage liver disesae,its senstivity was0.846, specificity was 0.887, accuracy was0.826.(12) FPP in experimental group were in direct correlation with HAP, and HPI, TTP (r=+0.263,+0.656,+0.563) but inverse correlation with PVP and TLP, of which FPP was in the best correlation with PVP (r=-0.816). Multiple regression, Stepwise regression internalized F test statisticsp<0.05 into regression equation, while F test statisticsp>0.05 rejected from the equation. Of the 5 perfusion parameters stated above, HAP,TLP and TTP were rejected, and PVP and HPI, the two variables, internalized to establish the optima regression equation: regression equation for portal venous pressure and perfusion parameters Y=17.175-0.173X1+0.135X2 (Y:FPP X1:PVP X2:HPI).The portal venous pressure was calculated with FPP and PVP, HPI linear regression equation, with the outcome as 12.7751±4.5631mmHg, the measured value 12.7867±5.4053mmHg, no statistics differences can be founded between them,t=6.129, P<0.001. We measured hepatic cirrhosis at the 95%confidence interval.The results showed that the diagnosis rates of sligthly hepatic fibrosis were 84.15%, 87.09%and 84.85%at early-stage liver cirrhosis,end-stage liver disease, respectively. Conclusion:1. The model-building from composite factor food of carbon tetrachloride (CCL4), agrypnal, absolute alcohol+high lipoids, low protein and low bilineurin can establish successfully the models of small pigs' end-stage liver disease.2. The liver volume,density,the caliber of the MVP and its main branch and perfusion parameters were changed in the end-stage liver disease group,compare to the other groups,and all had a better coefficient correlation with the Child-Pugh score,MELD score, ICGR15ICG. (3) The logistic regression analysis show that the liver volume, the caliber of the MVP,HPI and PVP were best indexs to evaluate the end-stage liver disease in mini-pigs.Used the cut point of ROC,the HPI=43.92%to diagnosis the end-stage liver disesae,its senstivity was0.846, specificity was 0.887, accuracy was0.826.4. The regression equation with PVP and HPI:Y=17.175-0.173X1+0.135X2 (Y:FPP X1: PVP X2:HPI), was optimal for calculation of FPP in evaluation the reserve function of the mini-pigs'end-stage liver disease.
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