Clinical Implications Of APRI In Assessment Of Liver Fibrosis In Infants With Cholestasis

Part 1 Diagnostic value of noninvasive tool APRI,SWE and FIB-4 in assessment of live fibrosis in cholestatic infantsBackground:An effective noninvasive tool to monitor liver fibrosis is important for cholestatic infants.This study is to investigate the predictive accuracy of aspartate aminotransferase to platelet ratio index(APRI)and to compare it with shear-wave elastography(SWE)and fibrosis-4(FIB-4).Methods:Patients:Cholestatic infants from the Women and Children Medical Hospital were enrolled between October 2016 and July 2018.A total of 121 infants were included in this stuy.Main measures:APRI and FIB-4 were calculated as following formulas:APRI=AST÷ULN/PLT×100(upper limit of normal[ULN]60U/L).FIB-4=AST×Age(years)/PLT×(?ALT[U/L]).Supersonic shearwave elastography(SWE)was performed to evaluate liver stiffnessA retrospective review of histologic findings of the liver was performed by two experienced pathologists blinded to the clinical patient data.The Metavil scoring system was used to assess liver fibrosis(F0,no fibrosis;F1,portal fibrosis without septa;F2,portal fibrosis with rare septa;F3,numerous septa and bridging fibrosis without cirrhosis;and F4,cirrhosis).Results:APRI demonstrated a positive correlation with fibrosis stage(r=0.511,p<0.001).FIB-4 also showed a positive correlation with the degree of fibrosis in cholestatic infants(r=0.470,P<0.001).And a stronger positive association between SWE and the degree of fibrosis was detected in cholestatic infants(r=0.730,p<0.001)APRI showed a highest diagnostic accuracy for the identification of the mild fibrosis and the moderate-to-severe fibrosis,when at a cutoff value?0.65 APRI can significantly differentiate F2-4 with sensitivity 73.5%and specificity 78.9%.That was followed by SWE which at a cutoff value of 12.OKp,it can significantly differentiate FO-1 from F2-4 with a sensitivity of 82.8%and a specificity of 61.5%.Compared to APRI and FIB-4,SWE had lager AUROC in predicting F3-4 and cirrhosis.The AUROC of SWE identification of cirrhosis was 0.92,and the sensitivity and specificity were 100%and 86.5%,respectively,when SWE?19.2Kp.Conclusion:Compared to SWE and FIB-4,APRI performs better for diagnosing fibrosis in cholestatic infants.And SWE is a more promising tool to detect advanced fibrosis and cirrhosis than APRI and FIB-4.Part 2 the role of APRI in early diagnosis of cystic biliary atresia and congenital choledochal cystBackground:Biliary cystic malformations(BCMs)are anomalies of the biliary tree characterised by cystic dilation of intra-or extrahepatic biliary ducts,including congenital choledochal cyst(CC)and cystic biliary atresia(CBA).CBA is a special subtype of biliary atresia,which is complicated by BCMs under the hepatic hilum,and can be easily misdiagnosed as CC.CBA has better clinical results than other types of biliary atresia,but early surgery is necessary for better surgical outcomes.So far,there is still difficulty in the early identification of CBA and CC clinically.This study analysed the differences in clinically objective indicators of CBA and CC groups to support differential diagnosisMethods:Patients:The clinical data of children with cholestatic liver disease in Guangzhou Women and Children's Medical Center from November 2012 to August 2016 were analysed retrospectively.A total of 53 children(22 with CBA and 31 with CC)were included in this study.Main measures:Clinical data including preoperative B-ultrasound,laboratory examination and APRI of the children were analysed retrospectively.The difference between the two groups was analysed,and diagnostic receiver operating characteristic(ROC)curve analysis was performed on indicators that showed statistical differences.Results:In total,53 children(22 children with CBA and 31 with CC)were included in this study.All the children underwent B-ultrasound examination before surgery.The mean cyst size was 15.9± 10.0 mm in the CBA group and 54.3±20.0 mm in the CC group(P<0.001).Further diagnostic ROC curve analysis indicated that the AUROC of cyst size identification of the CBA and CC groups was 0.96,and the sensitivity and specificity were 83,9%and 95.5%,respectively,at the best cut-off point of 3.5 cm.The APRI values were much lower in the CC group than in the CBA group(0.5±0.5 vs.1.1±0.9,P<0.001).?-GT values of the two groups were also higher than the normal level,but no significant difference was noted between the two groups.Further diagnostic ROC curve analysis showed that area under the receiver operating characteristic(AUROC)of DBIL identification of the CBA and CC groups was 0.88,and the sensitivity and specificity were 77.3%and 83.9%,respectively,at the best cut-off point of 98.5.The AUROC of APRI identification of the CBA and CC groups was 0.77,and the sensitivity and specificity were 95.5%and 58.1%,respectively,when APRI?0.37.Conclusion:There is still certain difficulty in the early identification of CBA and CC clinically.And APRI was not superior to B-ultrasound examination and DBIL in early identification of CBA and CCPart 3 APRI as noninvasive diagnostic tool for the degree of liver fibrosis in infants with biliary cystic malformations and association with postoperative prognosisBackground:For patients with CBA or CC,a stenotic distal bile duct or a blind-ending cyst may cause cholestatic jaundice.Therefore,a complication due to obstructive cholangiopathy can be the major pathology,which could lead to the development of liver fibrosis.Irreversible liver fibrosis could result in liver cirrhosis with unfavourable clinical course even after surgery.Detecting liver fibrosis in early stage is the pivotal issue in the treatment of patients with BCM.In recent years,aspartate aminotransferase-to-platelet ratio index(APRI)has been introduced as a non-invasive biochemical maker to reflect the degree of intrahepatic fibrosis.In patients with biliary atresia,APRI could effectively detect the degree of liver fibrosis,which is also associated with the degradation of Kasai postoperative jaundice.The role of APRI in the assessment of liver fibrosis and prediction of postoperative prognosis of BCM still requires further investigation.This study was to validate the value of APRI in the assessment of liver fibrosis and prediction postoperative outcome for infants with BCM.Methods:The clinical data of children with cholestatic liver disease in Guangzhou Women and Children's Medical Center from November 2012 to August 2016 were analysed retrospectively.A total of 53 children(22 with CBA and 31 with CC)were included in this study.Main measures:APRI?liverfibrosis(On the basis of the degree of liver fibrosis,these 40 children were categorised into mild fibrosis group F0-F2 and moderate-to-severe fibrosis group F3-F4.)?Postoperative evaluation indexes:cholangitis,secondary hospitalization,incidence of liver transplantation and mortality.Results:Among the 40 children who underwent intraoperative liver biopsy,the age at surgery was not significantly different between the CBA group and the CC group(78±37 days vs 68±41 days;P=0.218).These 40 children were categorised into two groups on the basis of the degree of fibrosis:26 children in the mild fibrosis group and 14 children in moderate-to-severe fibrosis group.The median age at surgery was 58±34 days in the mild fibrosis group and was 95±35 days in the moderate-to-severe fibrosis group.The difference between the two groups was statistically significant(P=0.001).The APRI values were much lower in the mild fibrosis groups than in the moderate-to-severe fibrosis group(0.4±0.2 vs.1.4±0.8,p<0.001).The predictive value of the APRI was evaluated using the ROC curve analysis and showed the best cut-off value of 0.96(AUC 0.92,P<0.001).Using this best cut-off value,APRI had a sensitivity of 81.3%and a specificity of 100%.When only the CBA category was evaluated,The APRI values were much lower in the mild fibrosis groups than in the moderate-to-severe fibrosis group(0.5±0.2 VS 1.5±0.9,P=0.003).The AUROC of APRI identification of the mild fibrosis groups and the moderate-to-severe groups was 0.89,and the sensitivity and specificity were 81.8%and 100%,respectively,when APRI?0.96.And for patients with CC,The APRI values were much lower in the mild fibrosis groups than in the moderate-to-severe fibrosis group(0.3±0.2 VS 1.4±0.5,P=0.002).The AUROC of APRI identification of the mild fibrosis groups and the moderate-to-severe groups was 0.97,and the sensitivity and specificity were 100%and 86.7%,respectively,at the best cut-off point of 0.57.In this study,42 children with BCMs(11 children in the CBA group and 31 children in the CC group)underwent surgery for the removal of obstruction and biliary reconstruction.The 42 children with BCMs were categorised into two groups:11 children in the APRI>0.96 group,and 31 children in the APRI<0.96 group.The TBIL and DBIL levels at a week after the surgery in the two groups of children were compared.The results reveal that the TBIL of the APRI>0.96 group(105.8±52.2)was obviously higher than that of the APRI<0.96 group(49.4±47.2;P?0.001);DBIL of the APRI>0.96 group was also much higher than that of the APRI?0.96 group(82.9± 44.6 vs.35.1±38.3;P?0.002).Fourteen of these 42 patients showed persisted jaundice a month after surgery and had higher preoperative APRI than the jaundice-free infants(1.0 ± 0.6 vs.0.4±0.4,/P=0·001).Conclusion:In infants with BCMs,APRI can be used as a non-invasive method to detecting liver fibrosis in early stage.And the correlation between the level of APRI and postoperative outcomes deserves further study.