Study Of Color Doppler Ultrasonography And Real-time Ultrasound Elastography In Diagnosis And Differential Diagnosis Of Infantile Hepatitis Syndrome And Hepatic Biliary Atresia

Part I:Study of Color Doppler Ultrasonography in Diagnosis and Differential Diagnosis of Infantile Hepatitis Syndrome and Hepatic Biliary AtresiaBackground and objective Infantile hepatitis syndrome (IHS) and biliary atresia (BA) are common cause of jaundice diseases in infancy. IHS is a syndrome of infants including jaundice, hepatomegaly/hepatosplenomegalia and hepatic dysfunction. BA is an infantile disorder characterized by the complete obstruction of a portion or the entire length of the hepatic bile duct caused by a fibro-inflammatory process that disrupts the flow of bile from the liver to the duodenum. There are two clinical types of BA:embryonal and perinatal. The incidence rate of perinatal type is90%. The complete obstruction extrahepatic bile duct is most common including three forms:type I (common bile duct atresia), type II (hepatic duct atresia), type III (hepatic portal bile duct atresia). The morbidity rate of BA in Asian is1/8000and that is the highest in China in the world. Because of bile duct complete obstruction, cholestasis, liver cells degeneration and fibrosis of infants with BA, their hepatic pathological changes are irreversible and further develop to cirrhosis and hepatic failure at last inescapably after three-month old. So early stage surgery is necessary, if not, infants will die before two-year old. There are two operative methods: hepatoportoenterostomy and liver transplantation. The liver transplantation of children is not carried out widely in our country because of lack of liver donor of transplantation and increasing of risk and cost of the operation. After40years of progress, Kasai-hepatoportoenterostomy has made the longterm survival improving significantly, meanwhile it has become the frist treatment option for BA. But operative opportunity is very important, because achievement rate of operation decreases with increased age in day of BA. The infants with BA lost the opportunity of operation after90-day old. There is no the long-term surviving of cases with Kasai-hepatoportoenterostomy after120-day old, and liver transplantation is the only treatment for BA. Research shows that the earlier the operation is did, the better prognosis will be and the higher totality survival rate is. Cholestatic IHS is a special pathological type of IHS that can be cure by medical treatment and bile duck irrigation. The therapeutic principle of others IHS is conservative medical management. The differential diagnosisa of IHS (cholestatic IHS, especially) and BA is the key, difficulty and a hot topic in research as a result of the overlap of clinical manifestations and the result of biochemical examination but principle of treatment is completely different. Ultrasonography is the preferred examination method for jaundice of infants. In this search, the ultrasonography diagnosis were contrasted with operation、pathology and clinical treatment results, and the aim was to evaluate application value of diagnosis and differential diagnosis in IHS and BAPatients and methods Eighty five infants with continual jaundice including48males and37females were observed. Their mean day-old was (69.54±36.17) days (range,4～182days). In them,40patients were cared by conservative treatment,17patients were cared by bile duck irrigation,16patients were operated by Kasai-hepatoportoenterostomy,12patients were operated by bile duct exploration,36patients’hepatic tissue were made pathological biopsy. They were divided into IHS and BA groups. IHS group were further divided into icteric IHS and cholestatic IHS groups.36infants were enrolled as control group including22males and14females. Their mean day-old was (62.07+29.26) days (range,9-120days) and they were met the following requirement:age and gender matching with the continual jaundice infants, without heart, lung, liver, spleen disease and liver function normal. The color Doppler ultrasound examination was performed with HIVSION Preirus. The medium frequency convex array probe (3-5MHz) and high frequency linear array probe(5～10MHz) were used. All infants were examed in the state of sleep at horizontal position for fasting4hours before treatment. To explorate with medium frequency convex array probe and high frequency linear array probe:(1) The size, shape and internal echo of liver and spleen; Status of left and right hepatic duct, extrahepatic biliary duct; The size and shape of fasting gallbladder and dynamic change at0.5h、1.0h、1.5h、2.0h、2.5h after meal (or to contraction rate be more than50%) of gallbladder. Recording the maximum length and anteroposterior diameter and calculating the gallbladder contraction rate; Observing triangular fibrotic mass and cysts in hepatic portal.(2) The parameters of portal vein (PV), hepatic artery (HA), splenic vein (SPV) and splenic artery (SPA) were measured. The PV and SPV parameters included anteroposterior diameter, transverse diameter and the mean velocity (Vpv、Vspv).The anteroposterior diameter was served as maximum diameter of PV and SPV (Dpv、Dspv). The HA parameters included anteroposterior diameter (DHA), the maximum velocity (VHA) and resistance index (RIHA).The SPA parameters included anteroposterior diameter (DSPA), the maximum velocity (VSPA) and resistance index (RISPA).Then parameters were calculated including:the flow of the PV (QPV), the congestion index of PV (CIPV), the flow of the SPV (Qspv), the congestion index of SPV (CIspv) and the rate of the velocity of HA and PV (A/P). Hepatic tissue pathological biopsy were divided into different period according to chronic hepatitis fibrosis staging criteria in revised plan for prevention and treatment of viral hepatitis in September2000. The parameters were analyzed with SPSS16.0statistics analysis software. When P<0.05, the difference was considered significant.Results1. There were32infants with icteric IHS that were treated by conservative treatment. There were25infants with cholestatic IHS, in them,8infants were cared by conservative treatment,17infants were cared by bile duck irrigation,15patients’ hepatic tissue was made pathological biopsy. There were28infants with BA, in them,16infants were operated by Kasai-hepatoportoenterostomy,12patients were operated by bile duct exploration,21patients’hepatic tissue was made pathological biopsy. There were8infants with type II BA and20infants with type III BA.2. Status about misdiagnosis:5patients were misdiagnosed. One infant with cholestatic IHS was misdiagnosed as BA. Four infants with BA were misdiagnosed as cholestatic IHS. The diagnosis accuracy of IHS and B A with ultrasound is94%.3. Results of gallbladder examinationThe size and shape of fasting gallbladder:There was significant difference between the control group, IHS group and BA group (P<0.01). There was not significant difference between icteric IHS group and cholestatic IHS group (P>0.05).The time of gallbladder contraction rate>50%after meal:That of the control group is0.5～1.5h, mean is (0.86±0.38) h; That of the icteric IHS group is0.5～ 2.0h, mean is (1.11±0.49) h; That of the cholestatic IHS group is0.75-2.5h, mean is (1.30±0.49) h. There was significant difference between the control group and icteric IHS group (P<0.05); There was significant difference between the control group and cholestatic IHS group (P<0.01); There was not significant difference between icteric IHS group and cholestatic IHS group (P>0.05). That time of1patient with cholestatic IHS was2.5h after meal.There were3types of gallbladder of8patients with type II BA:①Gallbladders of2patients were small, stiff and wall of that is crude. The gallbladder contraction rate of one was48%, the other one was no change after meal.②Fasting gallbladders of3patients were no filling and shape of that were normal. The gallbladder contraction rate were100%、100%、40%, respectively.③Size and shape of3patients’ gallbladders were normal. The gallbladder contraction rate were57%、40%、40%, respectively.There were4types of gallbladder of20patients with type III BA:①One patient’ gallbladder was not showed.②Gallbladder of1patient was streak high echo.③Gallbladders of17patients were small, stiff and wall of that were thick and crude. The antrum of part of patients’ gallbladder was crevice, and that of the part were atresia. The gallbladder contraction rate of3patients were7%、21%、30%, respectively. The others was no change after meal.④Gallbladder of1patient was normal size, stiff and wall of that was crude. It was no change after meal.There was significant difference between type II BA and type III BA in gallbladder contraction rate≥40%(P<0.01).4. Status about left and right hepatic duct, extrahepatic bile ductLeft and right hepatic duct, extrahepatic bile duct of the control group (36cases) and the icteric IHS group (32cases) were displayed (100%); Left and right hepatic duct, extrahepatic bile duct of24cases (96%) were displayed and1case (4%) was not displayed in cholestatic IHS group(25cases). In BA, left and right hepatic duct, extrahepatic bile duct of4patients (14%) with type II BA were displayed and that of24patients (86%) with type III B A were not displayed.The sensitivity, specificity and accuracy of diagnosing IHS and BA with left and right hepatic duct, extrahepatic bile duct were98%,86%,94%, respectively. The positive predictive value was93%and negative predictive value was96%.There was not significant difference between icteric IHS group and cholestatic IHS group (P>0.05) in left and right hepatic duct, extrahepatic bile duct. There was significant difference between icteric IHS group and BA group (P<0.01) in that. There was significant difference between cholestatic IHS group and BA group (P<0.01) in that. There was significant difference between type IIBA and type III BA (P<0.01) in that. There was significant difference between type II BA and cholestatic IHS group (P<0.01) in that.5. Status about cyst in hepatic portalThere were cysts in hepatic portal of2patients with cholestatic IHS. There were cysts in hepatic portal of5patients with type III BA.There was not significant difference between icteric IHS group and cholestatic IHS group (P>0.05) in cyst in hepatic portal. There was significant difference between icteric IHS group and BA group (P<0.05) in that. There was not significant difference between cholestatic IHS group and BA group (P>0.05) in that. There was not significant difference between type II BA and type III BA (P>0.05) in that.6. Status about fibrotic mass in hepatic portal.There were fibrotic mass in hepatic portal of24patients in28patients with BA with ultrasound, including4cases of type II BA and20cases type III BA. There were fibrotic mass in hepatic portal of26patients with BA in opetation, including6cases of type IIBA and20cases type III BA. The fibrotic mass in hepatic portal of 2patients with type IIBA were small that were not showed with ultrasound. There were no showed fibrotic mass in hepatic portal of57patients with IHS with ultrasound.There was not significant difference between type IIB A and type III BA (P>0.05) in fibrotic mass in hepatic portal in operation. There was significant difference between type II BA and type Ⅲ BA(P<0.05) in that with ultrasound.The sensitivity, specificity and accuracy of diagnosing BA with fibrotic mass in hepatic portal were92%,100%,86%, respectively.7. The result of hepatic tissue pathological biopsy:According to liver fibrosis stage,15patients with cholestatic IHS were divided into SO4cases, S16cases, S25cases, respectively.21patients with BA were divided into S23cases, S38cases, S410cases, respectively.8. Status about hemodynamic changeThere was not significant difference in DPV, QPV, VHA, DSPV, VSPV, QSPVv, CISPV, DSPA and VSPA between the control group, icteric IHS group, cholestatic IHS group and BA group (P>0.05).There was significant difference in VPV, CIPV, DHA, RIHA, A/P and RISPA between the BA group and the control group, icteric IHS group, cholestatic IHS group (P<0.05). The cutoff value of that were0.255m/s,68.384,2.116mm,0.738,3.151,0.704, respectively. There was significant difference in RIHA between the cholestatic IHS group and the control group, icteric IHS group (P<0.05).The Spearman’s correlation coefficient between VPV and the liver fibrosis stage was-0.742, which was highly significant (P<0.01). The Spearman’s correlation coefficient between RIHA and the liver fibrosis stage was0.666, which was significant (P<0.05). CIPV, DHA, A/P, RISPA were not significantly correlated with the liver fibrosis stage (P>0.05) Conclusion1. The diagnostic value of ultrasound examination is high for IHS and BA. It is suggested that the gallbladder contraction rate of infants with continual jaundice should be observed2.5h after meal.2. Type II BA is misdiagnosised as IHS frequently because of the feature of pathological changes and ultrasound images. Unobstructed common bile duct of type II BA is the reason that the overlap of gallbladder contraction rate in BA and IHS.3. RIHA of the cholestatic IHS is higher than that of icteric IHS and normal infants. There is no hemodynamic change of PV and spleen of IHS.4. DHA, RIHA, VPV, CIPV, A/P and RISPA are reliable parameters of hemodynamic change between BA and IHS. Part II:Contrast Study of Real-time Ultrasound Elastography and Pathology of Liver Fibrosis in Infantile Hepatitis Syndrome and Biliary AtresiaBackground and objective The virus that result in infantile hepatitis syndrome (IHS) bind the bile duct epitheliums with different affinities. That means the virus not only invades liver cells, but also invades the bile duct epitheliums, but the former is main. So the hepatic tissue pathological change of IHS is different from the virus hepatitis.The main representation of that is hepatic cell denaturation and necrosis, accompanied by various degree of inflammatory cell infiltrating mesenchyme and portal area, hepatic cell regenerating and fibrogenic, and small bile duct mild hyperplasia probable. In IHS, different degrees hepatic fibrosis is evident with the grade of liver lesion. The biliary passage systerm of biliary atresia (BA) is completely obstruction. In the early stage of BA, the bile deposits in hepatic cell and small bile duct, portal area is edematous and bile duct proliferates. In the later period, the bile duct develops strait and even atresia, the fibration appears in and around the portal area, hepatic lobules is damaged, the pseudolobuli and regenerative nodule form. It become biliary cirrhosis at last. The pathologic mechanism of hepatic fibrosis is following:The Kupffer cell activated by traces of bacteriotoxin and lipopolysaccharide produces a large number of cell factor. The hepatic stellate cell is activated by the cell factor. The extracellular matrixcell produced by activated hepatic stellate cell deposits in the portal area that lead to hepatic fibrosis. The progress of hepatic fibrosis of BA is obvious faster than that of hepatobiliary diseases of adult and infant else under the influence of multi-factor result in liver transplantation is necessary for BA. The degree of hepatic fibrosis contributed to differential diagnosis of IHS and BA. Meanwhile it is important significance for BA in evaluating the grade of liver lesions, choosing the operation chance and assessing postoperative outcome. The ultrasonic elasticity imaging is a new technique developed in recent years. The image-forming principle is following:The level of biological tissue deformation reflects the difference in hardness. Images of ultrasonic elasticity based on ultrasonic echo signal formed by displacement of deformation. Stiffness of the examined tissue is closely related to its pathological structure. So the pathological change can be estimated from the images of ultrasonic elasticity. The ultrasonic elasticity imaging has a few advantages, such as painless, non-invasive, fast, convenient, economic, repeatable and so on. It has been used to diagnose in the diseases of some superficial organs, such as thyroid and breast. It is applied in hepatic diseases to estimate hepatic fibrosis and has been paid attention increasingly. In this search, the real-time ultrasound elastography (RTE) contrasted with operation、pathology and clinical treatment results was studied to evaluate the value in IHS and BA. The aims were the following:①To select appropriate RTE plan for infants.②Whether RTE can diagnose hepatic fibrosis or not in IHS and BA.③To evaluate the correlations between RTE and the degree of hepatic fibrosis in IHS and BA.Patients and methods Twenty infants were enrolled as control group including12males and8females. Their mean day-old was (66.25+21.37) days (range,13～166days) and they were met the following requirement:age and gender matching with the continual jaundice infants, without heart, lung, liver, spleen disease and liver function normal.85infants with continual jaundice including48males and37females were observed. Their mean day-old was (69.54±36.17) days (range,4～182days). In them,40patients were cared by conservative treatment,17patients were cared by bile duck irrigation,16patients were operated by Kasai-hepatoportoentero-stomy,12patients were operated by bile duct exploration,36patients’ hepatic tissue were made pathological biopsy. They were divided into IHS and BA groups. IHS group were further divided into icteric IHS group and cholestatic IHS group. The data of patients made pathological biopsy were researched. The color Doppler ultrasound examination was performed with HIVSION Preirus. High frequency linear array probe (5～10MHz) were used. All infants were examed in the state of sleep at horizontal position for fasting4hours before treatment. RTE was performed in the control group using the right hepatic lobe oblique plane in right intercostal, the left hepatic lobe of transverse plan below the xiphoid and the left hepatic lobe of longitudinal plan below the xiphoid. It was observed that wether each plan imaging could be displayed distinctly or not and the result was record. The appropriate RTE plan according to the result was applied in85infants with continual jaundice, while probes were towards the heaet. Be about20mm from body surface, region of interest (ROI) was obtained without great vessels through. It is about10mm from liver surface and its area was about225mm2. Imagings were froze and stored at the trough when waves shape was stabile that formed by the heartbeat and respiratory movement stress liver. Three imagings were stored in the same plan every infant and than that were assigned the elasticity score by two sonographers with double-blind method. The score was analyzed comprehensively as final result. According to the proportion of color in ROI, imagings were marked from0to4point. The parameters were analyzed with SPSS16.0statistics analysis software. When P<0.05, the difference was considered significant.Results1. The cases of imaging displayed distinctly in right hepatic lobe oblique plane in right intercostal, in left hepatic lobe of transverse plan below the xiphoid and in left hepatic lobe of longitudinal plan below the xiphoid were2cases,5cases,18cases in the control group, respectively; The cases of imaging displayed undistinctly in that were18cases,15cases,2cases, respectively. There was significant difference in three plans.(P<0.01); There was not significant difference between in right hepatic lobe oblique plane in right intercostal and in left hepatic lobe of transverse plan below the xiphoid (P>0.05); There was significant difference between in left hepatic lobe of transverse plan below the xiphoid and in left hepatic lobe of longitudinal plan below the xiphoid.(P<0.01); There was significant difference between in right hepatic lobe oblique plane in right intercostal and in left hepatic lobe of longitudinal plan below the xiphoid.(P<0.01);2. Among18cases of the control group,14cases scored0point,3cases scored1point,1case scored2points.3.36patients’hepatic tissue were made pathological biopsy. In them, there were15cholestatic IHS and21BA. Score of RTE was significantly correlated with the liver pathological fibrosis stage (r=0.968, P<0.01)4. There was not significant difference between score of RTE and liver pathological biopsy in diagnosis of liver fibrosis in cholestatic IHS group and BA group(P>0.05).5. The sensitivity, specificity and accuracy of diagnosing liver fibrosis with score of RTE were97%,77%,88%, respectively. The positive predictive value was86%and negative predictive value was94%.6. Analysing score of RTE and liver pathological fibrosis stage in the control group, cholestatic IHS group and BA group:score of no liver fibrosis was0.27±0.55, score of liver fibrosis was2.61±1.05. There was significant difference between them (P<0.01,95%CI:-2.5842～-2.0961).7. RTE score of cholestatic IHS group is1.20±0.94. The score of BA group is3.05±0.92, There was significant difference between them (P<0.01).Conclusion1. The left hepatic lobe of longitudinal plan below the xiphoid is the appropriate RTE plan for infants.2. RTE contributes to assess liver fibrosis of infants and may reflects the degree of liver fibrosis3. RTE score is helpful in differential diagnosis of IHS and BA.