Experimental Study Of Rabbit Liver Function Impairment Evaluated By 2D Ultrasound And Tests And ARFI Combining With Pathology After Administration Of Chemotherapy

Objectives: To observe the ultrasonic characteristics,the measured values of acoustic radiation force impulse imaging(ARFI),the laboratory tests and pathological changes of rabbit liver caused by cisplatin and vinorelbine,and study the relationship between the findings with more attention to the degree of liver fatty impairment.Methods:Forty-four male New Zealand rabbits were randomly divided into 4 groups,control group(Group A),fat-diet group(Group B),cisplatin + vinorelbine group(Group C)and cisplatin + vinorelbine + fat-diet group(Group D).The liver function,blood lipid,conventional ultrasound and ARFI of the rabbit livers were taken before and after the treatment.After six cycles of drug(diet)administration,the above examinations were performed again.The data of lab test,conventional ultrasound and ARFI obtained before and after the treatment were compared.Finally,the rabbit liver pathology were performed.Results:Laboratory: There was no statistically significant difference for AST,ALT,TC,and TG in group A before and after treatment.AST and ALT increased in group B,group C and group D after treatment(t=22.806、23.994、54.386,both P< 0.05).AST in group D were higher than group C and group C were higher than group B.ALT in group D were higher than group B and group B were higher than group C.(F=791.103,1770.811,both P<0.05).TC and TG in group A and group C showed no statistically significant difference before and after treatment.TC and TG in group B and group D both increased after treatment than before(t=458.132,418.561,10.964,10.514,both P< 0.05),TC in group B were higher than group D,and group D were higher than group C and group A.TG in group B and group D were higher than group C and group A(F=2.494,74.844,both P<0.05).There were no statistically significant differences for TG between group B and group D,and between group C and group A after treatment.ARFI: There was no statistically significant difference in shear wave velocity before and after treatment in group A.Shear wave velocites in group B,group C and group D were increased after treatment(t=16.733,11.571,18.156,both P <0.05),the value of group D was higher than group B and group B was higher than group C(F=115.679,P<0.05).Ultrasound :There were no abnormal ultrasound findings in group A after treatment.Group B showed that the volume of liver was slightly enlarged,the shape was full,the capsule was smooth,the parenchymal echo was dense,enhanced and homogeneous.The echo of bile duct wall and portal vein wall was slightly enhanced,which was similar to that of mild fatty liver.Conventional ultrasound in group C after treatment shows thickening of liver capsule,varying degrees of increased and heterogeneous ehoes of parenchyma.The echoes of bile duct wall and portal vein wall were enhanced.In group D there was a little increase in hepatic volume and similar internal echoes as group C after treatment,and also there were enhanced and tense echoes of liver parenchyma,mimicking the sonogram of mild fatty liver.Pathology :There were no abnormal findings in group A before and after treatment.In group B after treatment there were obvious fatty degeneration.In group C after treatment there were hepatic hydropsy,mild sporadic fatty degeneration,inflammatory cell infiltration in portal area and in the walls of portal vein and bile duct.There were also some congestion and cholestasis,some spotty necrosis and fibroplasia.In group D after treatment there were also obvious fatty degeneration and some regenerative nodules besides the findings in group C.According to pathological classification,the pathological results of the above groups were classified and the receiver of operating characteristics curve(ROC)of the subjects were drawn.Roc curve analysis showed that there was no significant difference between TC and TG in diagnosing of mild liver fibrosis(p>0.05).Under curve area(AUC)of ARFI,AST and ALT for diagnosis of mild hepatic fibrosis were 0.863(95% confidence interval 0.744～0.981),0.835(95% confidence interval 0.708～0.962),0.835(95% confidence interval 0.704～0.966),The cut-off values of ARFI,AST and ALT was 1.4,68.685,90.795,the sensitivity was 71.4%,85.7%,57.1%,the specificity was 88.5%,76.9%,96.2%.Conclusion : Application of chemotherapeutants can cause different levels of pathological changes,but unlikely cause marked rabbit fatty liver,the so-called clinically chemotherapeutant-induced fatty liver probably results from the over intake of nutritious food.High fat diet can easily lead to increased TC and TG,causing abnormal liver function or aggravating liver impairment.ARFI has good value to evaluate the drug-induced liver damage.Laboratory test(AST and ALT)has high value for evaluating liver damage.