“Keyboard sign”and“coffee bean sign”in the prenatal diagnosis of ileal atresia:A case report

BACKGROUND Ileal atresia is a congenital abnormality where there is significant stenosis or complete absence of a portion of the ileum.The overall diagnostic accuracy of prenatal ultrasound in detecting jejunal and ileal atresia is low.We report a case of ileal atresia diagnosed prenatally by ultrasound examination with the“keyboard sign”and“coffee bean sign”.CASE SUMMARY We report a case of ileal atresia diagnosed in utero at 31 weeks'of gestation.Prenatal ultrasound examination revealed two rows of intestines arranged in an‘S’shape in the middle abdomen.The inner diameters were 1.7 cm and 1.6 cm,respectively.A typical“keyboard sign”was observed.The intestine canal behind the“keyboard sign”showed an irregular strong echo.There was no normal intestinal wall structure,showing a typical“coffee bean sign”.Termination of the pregnancy and autopsy findings confirmed the diagnosis.CONCLUSION The prenatal diagnosis of ileal atresia is difficult.The sonographic features of the“keyboard sign”and“coffee bean sign”are helpful in diagnosing the location of congenital jejunal and ileal atresia.

Reduction of the ages at diagnosis and operation of biliary atresia in Taiwan: A 15-year population-based cohort study

AIM: To describe the ages at diagnosis and operation of biliary atresia(BA) and its incidence over a 15-year period in Taiwan.METHODS: This was a population-based cohort study. BA cases were identified from the Taiwan National Health Insurance Research Database based on the International Classification of Diseases,Ninth Revision(ICD-9) code of BA 751.61 plus Kasai operation(ICD-9 procedure code 51.37) or liver transplantation(LT,ICD-9 procedure code 50.5). The patients' characteristics including sex,age at diagnosis,age at receiving Kasai operation and age at receiving LT were compared among three birth cohorts:(1) 1997 to 2001;(2) 2002 to 2006; and(3) 2007 to 2011.RESULTS: There were a total of 540 BA cases(275 females) with an incidence of 1.62 per 10000 live births. No seasonality of BA was noted. The mean ages at diagnosis of three cohorts were 57.9,55.6 and 52.6 d.A linear regression model demonstrated a decreasing trend of the mean age at diagnosis(1.27 d per year). The proportion of BA cases that received the Kasai operation within 60 d of age increased from 76% to 81%. A total of 189(35%) BA patients underwent LT. The mean age at LT was reduced from 3-year-old to 1-year-old. The rates of LT were 25.6% and 32.3% in patients who received the Kasai operation within 60 d or after 60 d of age,respectively. All patients who did not undergo a Kasai operation eventually required LT.CONCLUSION: The ages at diagnosis and operation in BA cases have decreased over time. Kasai operation performed at younger age reduces the need for LT. The incidence of BA in Taiwan fluctuates,but without certain trend.

Ultrasonic diagnosis of biliary atresia: A retrospective analysis of 20 patients

AIM: To investigate the clinical value of ultrasono-graphic diagnosis of biliary atresia (BA), a retrospective analysis of the sonogram of 20 children with BA was undertaken. METHODS: Ultrasonography (US) was performed in 20 neonates and infants with BA, which was confirmed with cholangiography by operation or abdominoscopy. The presence of triangular cord, the size and echo of liver, the changes in empty stomach gallbladder and postprandial gallbladder were observed and recorded. RESULTS: The triangular cord could be observed at the porta hepatis (thickness: 0.3-0.6 cm) in 10 cases. Smaller triangular cord (0.2-0.26 cm) can be observed in 3 cases. The gallbladder was not observed in 2 cases, and 1 case showed a streak gallbladder without capsular space. The gallbladders of 15 cases were flat and small. The gallbladders of 2 cases were of normal size and appearance, however, there was no postprandial contraction. The livers of all cases showed hepatomegaly and hetreogeneous echogenicity. Statistical analysis was performed to compare the hepatomegaly and hetreogeneous echogenicity and the stage of hepatic fibrosis. CONCLUSION: The presence of the triangular cord atthe porta hepatis is specific. However, it is not the only diagnostic criterion, since flat and small gallbladder and poor contraction are also of important diagnostic and differential diagnostic significance. The degree of hepatomegaly and hetreogeneous echogenicity is proportional with liver fibrosis, and able to indicate the duration of course and prognosis.

Diagnosis and treatment of biliary atresia: a retrospective study

BACKGROUND: Biliary atresia (BA) is the end results of an inflammatory process, which affect the intrahepatic and extrahepatic bile ducts, leading to fibrosis and obliteration of the biliary tract with the development of biliary cirrho- sis. Early diagnosis of BA is difficult, and there is no speci- fic therapy for BA at present. The purpose of this study was to investigate the diagnosis, treatment and postoperative outcome of BA and to explore new diagnostic and thera- peutic strategies. METHODS; Thirty-one children with biliary atresia from our hospital and 201 children with such disease from other hospitals in China were reviewed retrospectively in terms of diagnostic modalities, operative age, operative methods and long-term survival rates after operation. RESULTS : The operative age of the 31 patients varied from 13 to 270 days. It was <60 days in 6 children (19% ), 61-90 days in 14 (45% ), 91-120 days in 8 (26% ), and >120 days in 3 ( 10% ). No children underwent transplantation for BA. Their 1-6 year survival rate on average was 32. 3% (10/31). The early operative rate in China was 12.9% (30/ 232). One child received liver transplantation with a long- term survival rate of 31.9%. CONCLUSIONS; Early recognition of babies with BA is critical for optimal intervention for preventing progressive fibrosis. Clinical presentation, imaging and laparoscopy are helpful in enhancing the early diagnostic rate of BA pa- tients. The long-term survival rates can be obtained after the improvement of operative methods, liver transplanta- tion for children with advanced BA, and development of other medical strategies.

Validation of aspartate aminotransferase to platelet ratiofor diagnosis of liver fibrosis and prediction of postoperativeprognosis in infants with biliary atresia

Validation of aspartate aminotransferase to platelet ratiofor diagnosis of liver fibrosis and prediction of postoperativeprognosis in infants with biliary atresia pathological Metavir fibrosis score of the liver wedgespecimens of 91 BA infants. The prognostic value ofpreoperative APRI for jaundice persistence, liver injury,and occurrence of cholangitis within 6 mo after KP wasstudied based on the follow-up data of 48 BA infants.RESULTS： APRI was significantly correlated withMetavir scores （rs = 0.433; P 〈 0.05）. The mean APRIvalue was 0.76 in no/mild fibrosis group （Metavir scoreF0-F1）, 1.29 in significant fibrosis group （F2-F3）, and2.51 in cirrhosis group （F4） （P 〈 0.001）. The areaunder the ROC curve （AUC） of APRI for diagnosingsignificant fibrosis and cirrhosis was 0.75 （P 〈 0.001）and 0.81 （P = 0.001）, respectively. The APRI cut-offof 0.95 was 60.6% sensitive and 76.0% specific forsignificant fibrosis diagnosis, and a threshold of 1.66was 70.6% sensitive and 82.7% specific for cirrhosis.The preoperative APRI in infants who maintainedjaundice around 6 mo after KP was higher than thatin those who did not （1.86 ± 2.13 vs 0.87 ± 0.48, P 〈0.05）. The AUC of APRI for prediction of postoperativejaundice occurrence was 0.67. A cut-off value of0.60 showed a sensitivity of 66.7% and a specificityof 83.3% for the prediction of jaundice persistence.Preoperative APRI had no significant association withlater liver injury or occurrence of cholangitis.CONCLUSION： Our study demonstrated that APRIcould diagnose significant liver fibrosis, especiallycirrhosis in BA infants, and the elevated preoperativeAPRI predicts jaundice persistence after KP.

MR Cholangiography and Dynamic Examination of Duodenal Fluid inthe Differential Diagnosis between Extrahepatic Biliary Atresia and Infantile Hepatitis Syndrome

In order to evaluate the value of magnetic resonance cholangiography （MRC） and dynamic examination of duodenal fluid in the differential diagnosis between extrahepatic biliary atresia （EHBA） and infantile hepatitis syndrome （IHS）, 52 patients with infantile cholestatic jaundice were examined by MRC and duodenal fluid examination. Original interpretations were compared with clinical outcome. Calculated sensitivity of duodenal fluid examination in diagnosis of EHBA was 100 %, and specificity was 91.1%. Sensitivity of MRC in the diagnosis of EHBA was 94.4 % and specificity 88.24 %. The sensitivity of MRC and examination of duodenal fluid combined in diagnosis of EHBA was 94.4 % and specificity 97.06 %. We are led to conclude that MRC and dynamic examination of duodenal fluid are useful in the differential diagnosis between IHS and EHBA and the combined use of the two techniques yield better resutls.

Use of shear wave elastography for the diagnosis and follow-up of biliary atresia: A meta-analysis

BACKGROUND Timely differentiation of biliary atresia(BA)from other infantile cholestatic diseases can impact patient outcomes.Additionally,non-invasive staging of fibrosis after Kasai hepatoportoenterostomy has not been widely standardized.Shear wave elastography is an ultrasound modality that detects changes in tissue stiffness.The authors propose that the utility of elastography in BA can be elucidated through meta-analysis of existing studies.AIM To assess the utility of elastography in:(1)BA diagnosis,and(2)post-Kasai fibrosis surveillance.METHODS A literature search identified articles that evaluated elastography for BA diagnosis and for post-Kasai follow-up.Twenty studies met criteria for meta-analysis:Eleven for diagnosis and nine for follow-up post-Kasai.Estimated diagnostic odds ratio(DOR),sensitivity,and specificity of elastography were calculated through a random-effects model using Meta-DiSc software.RESULTS Mean liver stiffness in BA infants at diagnosis was significantly higher than in non-BA,with overall DOR 24.61,sensitivity 83%,and specificity 79%.Post-Kasai,mean liver stiffness was significantly higher in BA patients with varices than in patients without,with DOR 16.36,sensitivity 85%,and specificity 76%.Elastography differentiated stage F4 fibrosis from F0-F3 with DOR of 70.03,sensitivity 96%,and specificity 89%.Elastography also differentiated F3-F4 fibrosis from F0-F2 with DOR of 24.68,sensitivity 85%,and specificity 81%.CONCLUSION Elastography has potential as a non-invasive modality for BA diagnosis and surveillance post-Kasai.This paper’s limitations include inter-study method heterogeneity and small sample sizes.Future,standardized,multi-center studies are recommended.

Diagnosis of biliary strictures after liver transplantation:Which is the best tool?

AIM: To evaluate the diagnostic value of different indirect methods like biochemical parameters, ultrasound (US) analysis, CT-scan and MRI/MRCP in comparison with endoscopic retrograde cholangiography (ERC), for diagnosis of biliary complications after liver transplantation. METHODS: In 75 patients after liver transplantation, who received ERC due to suspected biliary complications, the result of the cholangiography was compared to the results of indirect imaging methods performed prior to ERC. The cholangiography showed no biliary stenosis (NoST) in 25 patients, AST in 27 and ITBL in 23 patients. RESULTS: Biliary congestion as a result of AST was detected with a sensitivity of 68.4% in US analysis (specificity 91%), of 71% in MRI (specificity 25%) and of 40% in CT (specificity 57.1%). In ITBL, biliary congestion was detected with a sensitivity of 58.8% in the US, 88.9%in MRI and of 83.3% in CT. However, as anastomotic or ischemic stenoses were the underlying cause of biliary congestion, the sensitivity of detection was very low. InMRI detected the dominant stenosis at a correct localization in 22% and CT in 10%, while US failed completely. The biochemical parameters, showed no significant difference in bilirubin (median 5.7; 4,1; 2.5 mg/dL), alkaline phosphatase (median 360; 339; 527 U/L) or gamma glutamyl transferase (median 277; 220; 239 U/L) levels between NoST, AST and ITBL.CONCLUSION: Our data confirm that indirect imaging methods to date cannot replace direct cholangiography for diagnosis of post transplant biliary stenoses. However MRI may have the potential to complement or precede imaging by cholangiography. Optimized MRCP-processing might further improve the diagnostic impact of this method.

Preoperative differential diagnosis between intrahepatic biliary cystadenoma and cystadenocarcinoma:A single-center experience

AIM: To investigate preoperative differential diagnoses made between intrahepatic biliary cystadenoma and intrahepatic biliary cystadenocarcinoma. METHODS: A retrospective analysis of patient data was performed, which included 21 cases of intrahepatic biliary cystadenoma and 25 cases of intrahepatic biliary cystadenocarcinoma diagnosed between April 2003 and April 2013 at the General Hospital of PLA. Potential patients were excluded whose diagnoses were not confirmed pathologically. Basic information (including patient age and gender), clinical manifestation, duration of symptoms, serum assay results (including tumor markers and the results of liver function tests), radiological features and pathological results were collected. All patients were followed up. RESULTS: Preoperative levels of cancer antigen 125 (12.51 +/- 9.31 vs 23.20 +/- 21.86, P < 0.05) and carbohydrate antigen 19-9 (22.56 +/- 26.30 vs 72.55 +/- 115.99, P < 0.05) were higher in the cystadenocarcinoma subgroup than in the cystadenoma subgroup. There were no statistically significant differences in age or gender between the two groups, or in pre- or post-operative levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin (TBIL), and direct bilirubin (DBIL) between the two groups. However, eight of the 21 patients with cystadenoma and six of the 25 patients with cystadenocarcinoma had elevated levels of TBIL and DBIL. There were three cases in the cystadenoma subgroup and six cases in the cystadenocarcinoma subgroup with postoperative complications. CONCLUSION: Preoperative differential diagnosis relies on the integration of information, including clinical symptoms, laboratory findings and imaging results. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

Recent advances in the diagnosis and treatment of primary biliary cholangitis

Primary biliary cholangitis(PBC), formerly referred toas primary biliary cirrhosis, is an infrequent progressive intrahepatic cholestatic autoimmune illness that can evolve into hepatic fibrosis, hepatic cirrhosis, hepatic failure, and, in some cases, hepatocellular carcinoma. The disease itself is characterized by T-lymphocytemediated chronic non-suppurative destructive cholangitis and elevated serum levels of extremely specific antimitochondrial autoantibodies(AMAs). In this article, we will not only review epidemiology, risk factors, natural history, predictive scores, radiologic approaches(e.g., acoustic radiation force impulse imaging, vibration controlled transient elastography, and magnetic resonance elastography), clinical features, serological characteristics covering biochemical markers, immunoglobulins, infections markers, biomarkers, predictive fibrosis marker, specific antibodies(including AMAs such as AMA-M2), anti-nuclear autoantibodies [such as anti-multiple nuclear dot autoantibodies(anti-sp100, PML, NDP52, anti-sp140), anti-rim-like/membranous anti-nuclear autoantibodies(anti-gp210, anti-p62), anti-centromere autoantibodies, and some of the novel autoantibodies], histopathological characteristics of PBC, diagnostic advances, and antidiastole of PBC. Furthermore, this review emphasizes the recent advances in research of PBC in terms of therapies, including ursodeoxycholic acid, budesonide, methotrexate, obeticholic acid, cyclosporine A, fibrates such as bezafibrate and fenofibrate, rituximab, mesenchymal stem cells transplant, and hepatic transplant. Currently, hepatic transplant remains the only optimal choice with acknowledged treatment efficiency for end-stage PBC patients.

Robotic-assisted Kasai portoenterostomy for child biliary atresia

BACKGROUND The Kasai procedure(KPE)is an important treatment for biliary atresia(BA),the most common cause of neonatal obstructive jaundice.AIM To investigate the efficacy of robotic-assisted Kasai portoenterostomy(RAKPE)in patients with BA.METHODS Clinical data of 10 patients with BA who underwent RAKPE at the Seventh Medi-cal Center of the People's Liberation Army General Hospital between December 2018 and December 2021 were retrospectively analyzed.One patient underwent Open Kasai portoenterostomy(OKPE)due to intraoperative bleeding.Consequ-ently,nine patients were included in this study.Fifty-two patients who under-went OKPE during the same period served as the control group.Preoperative and postoperative biochemical indexes,surgery-related indexes,and postoperative clearance of jaundice(CJ)were recorded and statistically analyzed.RESULTS RAKPE was successfully completed in all nine patients,with an average total operative time of 352.2 minutes(including intraoperative cholangiography).Milk feeding resumed on an average 9.89 days postoperatively,and the average time of drainage tube removal was 18.11 days.All patients were followed up for 6 mon-ths to 2 years.The liver function indicators and bilirubin levels in 8 patients returned to normal within 3 months after surgery.Three patients developed recu-rrent cholangitis after discharge,with elevated white blood cell counts,liver function indicators,and bilirubin levels,requiring hospitalization for intravenous antibiotic treatment.The duration of cholangitis ranged from 5 to 8 months post-surgery.To date,no subsequent cases of cholangitis have occurred.All patients have normal liver function and bilirubin levels,with no intrahepatic bile duct dilatation on ultrasonography.Statistical analysis comparing these indicators with those of patients who underwent OKPE showed that the RAKPE group had longer operative times and postoperative drainage tube removal durations.However,there were no significant differences in intraoperative blood loss,postoperative oral milk intake resumption,postoperative hospital stay,or CJ at 3 months post-surgery.CONCLUSION RAKPE is technically feasible,safe,and effective for treating BA.Once the technique is mastered,RAKPE may achieve CJ outcomes comparable to those of OKPE.

Primary liver transplantation vs transplant after Kasai portoenterostomy in children with biliary atresia: A retrospective Brazilian single-center cohort

BACKGROUND Biliary atresia(BA)is the most common indication for pediatric liver transplantation,although portoenterostomy is usually performed first.However,due to the high failure rate of portoenterostomy,liver transplantation has been advocated as the primary procedure for patients with BA.It is still unclear if a previous portoenterostomy has a negative impact on liver transplantation outcomes.AIM To investigate the effect of prior portoenterostomy in infants un-dergoing liver transplantation for BA.METHODS This was a retrospective cohort study of 42 pediatric patients with BA who underwent primary liver transplantation from 2013 to 2023 at a single tertiary center in Brazil.Patients with BA were divided into two groups:Those undergoing primary liver transplantation without portoenterostomy and those undergoing liver transplantation with prior portoenterostomy.Continuous variables were compared using the Student’s t-test or the Kruskal-Wallis test,and categorical variables were compared using theχ2 or Fisher’s exact test,as appropriate.Multivariable Cox regression analysis was performed to determine risk factors for portal vein thrombosis.Patient and graft survival analyses were conducted with the Kaplan–Meier product-limit estimator,and patient subgroups were compared using the two-sided log-rank test.RESULTS Forty-two patients were included in the study(25[60%]girls),23 undergoing liver transplantation without prior portoenterostomy,and 19 undergoing liver transplantation with prior portoenterostomy.Patients with prior portoenterostomy were older(12 vs 8 months;P=0.02)at the time of liver transplantation and had lower Pediatric End-Stage Liver Disease scores(13.2 vs 21.4;P=0.01).The majority of the patients(35/42,83%)underwent livingdonor liver transplantation.The group of patients without prior portoenterostomy appeared to have a higher incidence of portal vein thrombosis(39 vs 11%),but this result did not reach statistical significance.Prior portoenterostomy was not a protective factor against portal vein thrombosis in the multivariable analysis after adjusting for age at liver transplantation,graft-to-recipient weight ratio,and use of vascular grafts.Finally,the groups did not significantly differ in terms of post-transplant survival.CONCLUSION In our study,prior portoenterostomy did not significantly affect the outcomes of liver transplantation.

S100 calcium binding protein A6 and associated long noncoding ribonucleic acids as biomarkers in the diagnosis and staging of primary biliary cholangitis

BACKGROUND Primary biliary cholangitis(PBC)is a chronic and slowly progressing cholestatic disease,which causes damage to the small intrahepatic bile duct by immunoregulation,and may lead to cholestasis,liver fibrosis,cirrhosis and,eventually,liver failure.AIM To explore the potential diagnosis and staging value of plasma S100 calcium binding protein A6(S100A6)messenger ribonucleic acid(mRNA),LINC00312,LINC00472,and LINC01257 in primary biliary cholangitis.METHODS A total of 145 PBC patients and 110 healthy controls(HCs)were enrolled.Among them,80 PBC patients and 60 HCs were used as the training set,and 65 PBC patients and 50 HCs were used as the validation set.The relative expression levels of plasma S100A6 mRNA,long noncoding ribonucleic acids LINC00312,LINC00472 and LINC01257 were analyzed using quantitative reverse transcription-polymerase chain reaction.The bile duct ligation(BDL)mouse model was used to simulate PBC.Then double immunofluorescence was conducted to verify the overexpression of S100A6 protein in intrahepatic bile duct cells of BDL mice.Human intrahepatic biliary epithelial cells were treated with glycochenodeoxycholate to simulate the cholestatic environment of intrahepatic biliary epithelial cells in PBC.RESULTS The expression of S100A6 protein in intrahepatic bile duct cells was up-regulated in the BDL mouse model compared with sham mice.The relative expression levels of plasma S100A6 mRNA,log10 LINC00472 and LINC01257 were upregulated while LINC00312 was down-regulated in plasma of PBC patients compared with HCs(3.01±1.04 vs 2.09±0.87,P<0.0001;2.46±1.03 vs 1.77±0.84,P<0.0001;3.49±1.64 vs 2.37±0.96,P<0.0001;1.70±0.33 vs 2.07±0.53,P<0.0001,respectively).The relative expression levels of S100A6 mRNA,LINC00472 and LINC01257 were up-regulated and LINC00312 was down-regulated in human intrahepatic biliary epithelial cells treated with glycochenodeoxycholate compared with control(2.97±0.43 vs 1.09±0.08,P=0.0018;2.70±0.26 vs 1.10±0.10,P=0.0006;2.23±0.21 vs 1.10±0.10,P=0.0011;1.20±0.04 vs 3.03±0.15,P<0.0001,respectively).The mean expression of S100A6 in the advanced stage(III and IV)of PBC was up-regulated compared to that in HCs and the early stage(II)(3.38±0.71 vs 2.09±0.87,P<0.0001;3.38±0.71 vs 2.57±1.21,P=0.0003,respectively);and in the early stage(II),it was higher than that in HCs(2.57±1.21 vs 2.09±0.87,P=0.03).The mean expression of LINC00312 in the advanced stage was lower than that in the early stage and HCs(1.39±0.29 vs 1.56±0.33,P=0.01;1.39±0.29 vs 2.07±0.53,P<0.0001,respectively);in addition,the mean expression of LINC00312 in the early stage was lower than that in HCs(1.56±0.33 vs 2.07±0.53,P<0.0001).The mean expression of log10 LINC00472 in the advanced stage was higher than those in the early stage and HCs(2.99±0.87 vs 1.81±0.83,P<0.0001;2.99±0.87 vs 1.77±0.84,P<0.0001,respectively).The mean expression of LINC01257 in both the early stage and advanced stage were up-regulated compared with HCs(3.88±1.55 vs 2.37±0.96,P<0.0001;3.57±1.79 vs 2.37±0.96,P<0.0001,respectively).The areas under the curves(AUC)for S100A6,LINC00312,log10 LINC00472 and LINC01257 in PBC diagnosis were 0.759,0.7292,0.6942 and 0.7158,respectively.Furthermore,the AUC for these four genes in PBC staging were 0.666,0.661,0.839 and 0.5549,respectively.The expression levels of S100A6 mRNA,log10 LINC00472,and LINC01257 in plasma of PBC patients were decreased(2.35±1.02 vs 3.06±1.04,P=0.0018;1.99±0.83 vs 2.33±0.96,P=0.036;2.84±0.92 vs 3.69±1.54,P=0.0006),and the expression level of LINC00312 was increased(1.95±0.35 vs 1.73±0.32,P=0.0007)after treatment compared with before treatment using the paired t-test.Relative expression of S100A6 mRNA was positively correlated with log10 LINC00472(r=0.683,P<0.0001);serum level of collagen type IV was positively correlated with the relative expression of log10 LINC00472(r=0.482,P<0.0001);relative expression of S100A6 mRNA was positively correlated with the serum level of collagen type IV(r=0.732,P<0.0001).The AUC for the four biomarkers obtained in the validation set were close to the training set.CONCLUSION These four genes may potentially act as novel biomarkers for the diagnosis of PBC.Moreover,LINC00472 acts as a potential biomarker for staging in PBC.

Intrauterine diagnosis of proximal jejunal atresia in a neonate conceived by assisted conception technique: a case report

Jejunal atresia is an entity within an array of congenital intestinal anomalies. We present a case of antepartum diagnosis of proximal jejunal atresia in a baby conceived through assisted conception.

Beyond the Pediatric end-stage liver disease system: Solutions for infants with biliary atresia requiring liver transplant

Biliary atresia(BA), a chronic progressive cholestatic disease of infants, is the leading cause for liver transplant in children, especially in patients under two years of age. BA can be successfully treated with the Kasai portoenterostomy; however most patients still require a liver transplant, with up to one half of BA children needing a transplant by age two. In the current pediatric end-stage liver disease system, children with BA face the risk of not receiving a liver in a safe and timely manner. In this review, we discuss a number of possible solutions to help these children. We focus on two general approaches:(1) preventing/delaying need for transplantation, by optimizing the success of the Kasai operation; and(2) expediting transplantation when needed, by performing techniques other than the standard deceased-donor, whole, ABO-matched organ transplant.

Assessment of liver fibrosis by Fibroscan as compared to liver biopsy in biliary atresia

AIM: To evaluate liver stiffness measurement(LSM)using non-invasive transient elastography(Fibroscan)in comparison with liver biopsy for assessment of liver fibrosis in children with biliary atresia(BA).METHODS: Thirty-one children with BA admitted to the Department of Pediatric Surgery of Beijing Children's Hospital from March 2012 to February 2013 were included in this study. Their preoperative LSM, liver biopsy findings, and laboratory results were studied retrospectively.RESULTS: The grade of liver fibrosis in all 31 patients was evaluated according to the METAVIR scoring system, which showed that 4 cases were in group F2, 20 in group F3 and 7 in group F4. There were 24non-cirrhosis cases(F2-F3) and 7 cirrhosis cases(F4).In groups F2, F3 and F4, the mean LSM was 9.10 ±3.30 kPa, 11.02 ± 3.31 kPa and 22.86 ± 12.43 kPa,respectively. LSM was statistically different between groups F2 and F4(P = 0.002), and between groups F3 and F4(P = 0.000), however, there was no statistical difference between groups F2 and F3(P = 0.593). The area under the receiver operating characteristic curve of LSM for ≥ F4 was 0.866. The cut-off value of LSM was 15.15 kPa for ≥ F4, with a sensitivity, specificity,positive predictive value and negative predictive value of 0.857, 0.917, 0.750 and 0.957, respectively.CONCLUSION: Fibroscan can be used as a noninvasive technique to assess liver fibrosis in children with BA. The cut-off value of LSM(15.15 kPa) can distinguish cirrhotic patients from non-cirrhotic patients.

Increased osteopontin and liver stiffness measurement by transient elastography in biliary atresia

AIM: To analyze plasma osteopontin levels and liver stiffness using transient elastography in postoperative biliary atresia (BA) children compared with healthy controls. METHODS: Thirty children with postoperative BA and 10 normal controls were enrolled. The patients were categorized into two groups according to their jaundicestatus. Plasma levels of osteopontin were determined using commercially available enzyme-linked immunosorbent assay. Liver stiffness was measured by using transient elastography (Fibroscan). Ten validated Fibroscan measurements were performed in each patient and control with the result expressed in kilopascals (kPa). RESULTS: Plasma osteopontin was significantly elevated in BA children compared with that of healthy controls (47.0 ± 56.4 ng/mL vs 15.1 ± 15.0 ng/mL, P = 0.01). The liver stiffness measurement was markedly elevated in the patients with BA compared with that of controls (26.9 ± 24.6 kPa vs 3.9 ± 0.7 kPa, P = 0.001). Subgroup analysis showed that the BA patients with jaundice had more pronounced plasma osteopontin levels than those without jaundice (87.1 ± 61.6 ng/mL vs 11.9 ± 6.1 ng/mL, P = 0.001). Furthermore, the mean liver stiffness was significantly greater in the jaundiced BA patients compared with non-jaundiced patients (47.7 ± 21.8 kPa vs 8.7 ± 3.0 kPa, P = 0.001). Additionally, plasma osteopontin was positively related to serum total bilirubin (r = 0.64, P < 0.001). There was also a correlation between plasma osteopontin and liver stiffness values (r = 0.60, P < 0.001). CONCLUSION: High plasma osteopontin positively correlated with degree of hepatic fibrosis and could be used as a biochemical parameter reflecting disease severity in postoperative BA children.

Liver transplantation for biliary atresia: A single-center study from China's Mainland

AIM: To summarize our single-center experience with liver transplantation(LT) for biliary atresia(BA).METHODS: From October 2006 to December 2012, 188 children with BA were analyzed retrospectively. The stage?Ⅰ?group(from October 2006 to December 2010) comprised the first 74 patients, and the stage Ⅱ group(from January 2011 to December 2012) comprised the remaining 114 patients. Finally, 123 liver transplants were performed in 122(64.9%) patients, whereas 66 patients did not undergo LT due to denial by their parents or lack of suitable liver grafts. The selection of graft types depended on the patients' clinical status and whether a suitable living donor was available. The characteristics of patients in stages?Ⅰ?and Ⅱ were described, and the surgical outcomes of LT recipients were compared between the two stages. The KaplanMeier method was used to estimate the cumulative patient and graft survival rates, and the equality of survival distributions was evaluated using the log-rank test.RESULTS: The 188 children consisted of 102 boysand 86 girls. Their ages ranged from 3 to 144 mo with a median of 8 mo. One hundred and fifteen(61.2%) patients were born in rural areas. Comparing stage?Ⅰ?and stage Ⅱ patients, the proportion of patients referred by pediatricians(43.2% vs 71.1%, respectively; P < 0.001) and the proportion of patients who previously received a Kasai procedure(KP)(32.4% vs 44.7%, respectively; P = 0.092) obviously increased, and significantly more parents were willing to treat their children with LT(73% vs 86%, respectively; P = 0.027). Grafts from living donors(102/122, 83.6%) were the most commonly used graft type. Surgical complications(16/25, 64.0%) were the main reason for posttransplant mortality. Among the living donor liver transplantation recipients(n = 102), the incidence of surgical complications was significantly reduced(34.1% vs 15.5%, respectively; P = 0.029) and survival rates of patients and grafts were greatly improved(81.8% vs 89.7%, respectively, at 1 year; 75.0% vs 87.8%, respectively, at 3 years; P = 0.107) from stage?Ⅰ?to stage Ⅱ.CONCLUSION: The status of surgical treatments for BA has been changing in China's Mainland. Favorable midterm outcomes after LT were achieved as centers gained greater technical experience.

Role of CD56-expressing immature biliary epithelial cells in biliary atresia

AIM: To analyze the clinical and pathological parameters and expression of the neural cell adhesion molecule(CD56) in patients with biliary atresia(BA).METHODS: Established clinical laboratory markers of hepatic function, including enzyme activity, protein synthesis, and bilirubin metabolism, were evaluated in patients with BA and compared with those in patients with choledochal cysts and neonatal hepatitis. Pathological changes in tissue morphology and fibrosis were examined by histological and tissue collagen staining. Immunohistochemical staining for the biliary epithelial cell markers CD56 and CK19 together with the Notch signaling related molecules Notch1 and Notch2 was performed in the context of alterations in the structure of intrahepatic biliary ducts.RESULTS: Differences in some clinical laboratoryparameters among the three diseases examined were observed, but they did not correlate with the pathological classification of fibrosis in BA. Immunohistochemical staining showed the presence of CD56-positive immature bile ducts in most patients(74.5%) with BA but not in patients with choledochal cysts or neonatal hepatitis. The number of CD56-expressing cells correlated with disease severity, with more positive cells present in the later stages of liver damage(81.8% vs 18.2%). Furthermore, bile plugs were mainly found in CD56-positive immature biliary ducts. Notch signaling was a key regulatory pathway in biliary duct formation and played a role in tissue fibrosis. Notch1 was co-expressed in CD56-positive cells, whereas Notch2 was found exclusively in blood vessels in the portal area of patients with BA. CONCLUSION: The maturation of biliary epithelial cells and the expression of Notch may play a role in the pathogenesis of BA.

Diagnosis and management of choledocholithiasis in the golden age of imaging, endoscopy and laparoscopy

Biliary lithiasis is an endemic condition in both Western and Eastern countries, in some studies affecting 20% of the general population. In up to 20% of cases, gallbladder stones are associated with common bile duct stones (CBDS), which are asymptomatic in up to one half of cases. Despite the wide variety of examinations and techniques available nowadays, two main open issues remain without a clear answer: how to cost-effectively diagnose CBDS and, when they are finally found, how to deal with them. CBDS diagnosis and management has radically changed over the last 30 years, following the dramatic diffusion of imaging, including endoscopic ultrasound (EUS) and magnetic resonance cholangiography (MRC), endoscopy and laparoscopy. Since accuracy, invasiveness, potential therapeutic use and cost-effectiveness of imaging techniques used to identify CBDS increase together in a parallel way, the concept of &#x0201c;risk of carrying CBDS&#x0201d; has become pivotal to identifying the most appropriate management of a specific patient in order to avoid the risk of &#x0201c;under-studying&#x0201d; by poor diagnostic work up or &#x0201c;over-studying&#x0201d; by excessively invasive examinations. The risk of carrying CBDS is deduced by symptoms, liver/pancreas serology and ultrasound. &#x0201c;Low risk&#x0201d; patients do not require further examination before laparoscopic cholecystectomy. Two main &#x0201c;philosophical approaches&#x0201d; face each other for patients with an &#x0201c;intermediate to high risk&#x0201d; of carrying CBDS: on one hand, the &#x0201c;laparoscopy-first&#x0201d; approach, which mainly relies on intraoperative cholangiography for diagnosis and laparoscopic common bile duct exploration for treatment, and, on the other hand, the &#x0201c;endoscopy-first&#x0201d; attitude, variously referring to MRC, EUS and/or endoscopic retrograde cholangiography for diagnosis and endoscopic sphincterotomy for management. Concerning CBDS diagnosis, intraoperative cholangiography, EUS and MRC are reported to have similar results. Regarding management, the recent literature seems to show better short and long term outcome of surgery in terms of retained stones and need for further procedures. Nevertheless, open surgery is invasive, whereas the laparoscopic common bile duct clearance is time consuming, technically demanding and involves dedicated instruments. Thus, although no consensus has been achieved and CBDS management seems more conditioned by the availability of instrumentation, personnel and skills than cost-effectiveness, endoscopic treatment is largely preferred worldwide.