Evaluation Of Immune Liver Injury Induced By PD-1 Inhibitor In Experimental Rabbits By Two-dimensional Shear Wave Elastography

ObjectiveTo explore the evaluation of immune liver injury in experimental rabbits by conventional two-dimensional ultrasound and two-dimensional shear wave elastography(2D-SWE),and compare it with pathological findings,so as to more truly and accurately reflect the diagnostic value of conventional ultrasound and swe in immune liver injury in experimental rabbits.Methods42 healthy male New Zealand white rabbits were randomly divided into two groups,including 30 in the experimental group and 12 in the control group.During the experiment,the experimental group and the control group ate normally,and the eating,drinking,fur,weight change and activity of the experimental rabbits were continuously observed.Four rabbits were randomly selected from the experimental group before(TO)and the second week(T1),the fourth week(T2),the sixth week(T3)and the eighth week(T4)after administration.Two rabbits were randomly selected from the control group.All white rabbits in the experimental group and the control group were selected in the 12th week(T5).After fasting for at least 8 hours,blood was drawn through the middle ear artery for liver function examination,The skin preparation was anesthetized and fixed on the fixed plate,the examination area was fully exposed,and routine ultrasonography was performed to observe the morphology,capsule,parenchymal echo,gallbladder and ascites of the liver.Then enable swe mode,and take the depth from the upper edge of the sampling frame to the surface of the liver capsule as the grouping basis of different measurement depths,starting from close to the liver capsule(0.5cm away from the liver capsule)to 1.4cm away from the liver capsule,each 0.3cm is divided into four groups.Measure the average value of Young’s modulus Emean(kPa)at different depths of the liver and record it as SWE 1,SWE2,SWE3 and SWE4.After that,all experimental rabbits were killed by air embolism.The liver tissue was taken and sent to the Department of pathology.It was fixed with 10%formalin for 24 hours.Then,he staining and Masson staining were performed after routine paraffin embedded sections,and observed under the microscope.Finally,all data were statistically analyzed.Result1.General information of experimental rabbits:The control group was generally in good condition without death.The experimental group had poor mental condition,poor appetite,binaural fungal infection,rabbit hair disheveled or falling off,and the weight of the experimental group was less than that of the control group after the end of the experiment.There was no death.2.Ultrasonic examination:2.1 conventional two-dimensional ultrasound:Control group:in to～T5 stage,the liver parenchyma was uniform without obvious abnormal changes;The liver envelope was smooth,the size was normal,the lower edge of liver was sharp,and the thickness of gallbladder wall had no significant difference in each stage(P>0.05);Experimental group:from to to T2,the echo of liver parenchyma was uniform,the capsule was smooth,the lower edge of liver was sharp,and there was no ascites;From T3 to T4,the echo of liver parenchyma increased,thickened and enhanced,the capsule was smooth,the lower edge of liver was slightly incarcerated,and ascites was formed;In T5 stage,the liver capsule is still smooth,the lower edge is slightly incarcerated,the echo of parenchyma is uniform and enhanced,and there is no ascites;2.2 real time shear wave elastic imaging:Control group:there was no significant difference in swe value between t0 and T5 stages(P>0.05);There was no significant difference in Swe1,swe2,swe3 and swe4 at different depths in the same period(P>0.05).Experimental group:the emean values of rabbit liver fibrosis in SO stage,S1 stage,S2 stage and S3 stage were(4.18±0.37)kPa,(4.51±0.49)kPa,(5.89±1.33)kPa and(8.57±1.66)kPa respectively.The relationship between the emean values of liver in each stage was S0<S1<S2<S3.There was significant difference in one-way ANOVA of emean value between different stages(F=49.685,P<0.01),and the difference between any two periods was also statistically significant(P<0.05),Conclusion1.When teripulimab was injected into the ear vein of experimental rabbits at the dose of 15mg/(kg·2w),the immune injury of the liver of experimental rabbits would change,and the degree of liver injury would aggravate with the increase of medication cycle.2.Liver emean value can be used for noninvasive diagnosis of immune liver injury in experimental rabbits.Swe can better distinguish different degrees of liver fibrosis.It can be used as a quantitative index for noninvasive evaluation of the process of immune liver injury,and has a good clinical application prospect.