A prognostic analysis of cystic and non-cystic biliary atresia.

Cystic biliary atresia: an etiologic and prognostic subgroup

Objective To explore the clinical characteristics and prognosis of cystic biliary atresia (BA) in prenatal fetuses. Methods From October 2012 to October 2017, retrospective analysis was performed for 10 patients with cystic BA were traced from antenatal, including Doppler ultrasound, magnetic resonance imaging (MRI) in pernatal period and clinical manifestations and Doppler ultrasound, MRI and intraoperative cholangiography in postnatal period.Based upon the findings of interoperative cholangiography, the clinical types were Ⅰ (treelike), Ⅰ (cloudiness) and Ⅲd.Blood biochemical results, native liver survival and prognosis were collected and analyzed at preoperation and postoperation.SPSS 17.0 was employed for evaluating operative effects.And 89 cases of cystic BA were retrieved from the databases of PubMed, Embase, CNKI, Wangfang and VIP prior to October 2017. Results Prenatal ultrasonography: All cases showed cystic lesions of cycloidal, inerratic and high tension in gestation and nearly equirotal during gestation.Pre- and post-prenatal MRI: Type Ⅰ showed cystic lesions of oval, relatively inerratic and high tension in gestation with a high signal of cyst wall; Type Ⅲd showed cystic lesions of cycloidal, inerratic and high tension in gestation with cyst wall without a high signal.Interoperative cholangiography and exploration of biliary tract: the clinical types were Ⅰ (treelike) (n=3), Ⅰ (cloudiness) (n=3) and Ⅲd (n=4). All patients were operated.Biochemistry: AST/ALT: Biochemical results of type Ⅰ (treelike) gradually declined to normal.Biochemical results of type Ⅰ (cloudiness) gradually improved after 6 months and 18-month follow-up outcome was unfavorable (P<0.05). Biochemical results of Ⅲd declined gradually within 6 months and increased again within 18 months (P<0.05). TBIL/DBIL: Bilirubin results of type Ⅰ BA (treelike) gradually declined to normal within 1 month.Type Ⅰ (cloudiness) gradually improved within 3 months and 6-month follow-up showed a marked increase (P<0.05). Ⅲd declined within 3-6 months and increased again within 18 months (P<0.05). A total of 13 studies involving 89 patients were diagnosed as cystic BA and 10 patients of our study were also included. Conclusions Doppler ultrasound and MRI in pernatal may preliminarily differentiate cystic BA and choledochal cyst.Early diagnosis and prompt treatment two months are of vital importance.Based upon jaundice disappearance time and native liver survival, type Ⅰ (treelike) has the best prognosis. Key words: Biliary atresia; Surgery; Prognosis

The aim of the study is to determine the prognosis of patients with biliary atresia after 2 years of native liver survival (NLS) and to identify prognostic factors for continued NLS after 2 years of age. We retrospectively analyzed perioperative, laboratory, and outcome parameters of all biliary atresia patients in The Netherlands between January 1987 and June 2015 with NLS of at least 2 years. We compared parameters between patients who continued to have their native liver (NLS+) to those who did not, either by transplant or death (NLS-). We included 100 patients. Upon a median follow-up of 16.4 years, NLS ended in 37% by liver transplantation (LTx) and in 6% by (pre-transplant) mortality. NLS rates at 5, 10, 15, 18 years of age were 89%, 72%, 60%, 54%, respectively. Corresponding overall survival rates were 98%, 90%, 87%, 87%, respectively. Six months post-Kasai, NLS+ patients had higher clearance of jaundice (COJ) rate, significantly lower total and direct serum bilirubin, aspartate-aminotransferase and alkaline phosphatase levels, compared with NLS- patients (each P < 0.05). Cox regression could only assess a significant effect of COJ on continued NLS. Main indications for LTx after the age of 2 were irreversible jaundice and portal hypertension. Eighty-seven percent of patients with 2-year NLS reach adult age and more than 50% with their native liver. A pre-transplant mortality of 6%, however, exists among patients who reach the age of 2 years with their native livers. Early life parameters, other than COJ, did not have a significant effect on continued NLS after 2 years of age.

The exact nature of the relationship between age at Kasai portoenterostomy (KP) for biliary atresia (BA) and outcome is controversial. Single-center retrospective analysis of consecutive cases (January 1994-December 2005) undergoing KP, using 2 dichotomous measures of outcome (clearance of jaundice to <20 micromol/L and native liver survival at 2 years post-KP). Outcome was analyzed by age cohort (<30 days, 30-40 days, etc) and cumulatively. Data are quoted as median (interquartile range). Statistical analysis was by extended Fisher r x c analysis. P < 0.05 was regarded as significant. Two hundred twenty-five infants with BA were divided into 3 groups based on possible etiology: isolated BA (n = 177), biliary atresia splenic malformation (BASM) syndrome (n = 28), and cystic BA (n = 23). Three infants had both BASM and a cyst. Age at KP was significantly greater in those with isolated BA [58 (48-61)] compared with both BASM [47 (39-59); P = 0.02] and cystic BA [47 (39-54); P = 0.02]. Overall, 127 (56%) cleared their jaundice and 145 (65%) survived to 2 years with their native liver. Children with isolated BA showed no statistical difference by age cohort for clearance of jaundice (P = 0.75) or for native liver survival (P = 0.14). In contrast, there was a marked detrimental effect of age at KP for both BASM and cystic BA groups (P = 0.02). There is a marked detrimental effect of age at KP on groups with a presumed "developmental" origin, not seen in the majority with isolated BA.

Cystic biliary atresia is a rare (5-10%) variant of type I biliary atresia. The present report intends to share our experience with cystic variant of biliary atresia along with a review of pertinent literature. The first case was a 3-month-old infant with cholestatic jaundice with preoperative diagnosis of an infantile type of choledochal cyst. The second case was a 4-month-old twin infant with cholestatic jaundice and with preoperative differential diagnoses of either cystic biliary atresia or an infantile type of choledochal cyst (cyst located within the hepatic hilum). Cystic biliary atresia was confirmed intra-operatively in both the patients. In first infant, Kasai portoenterostomy procedure was performed, while in the second patient hepaticoduodenostomy procedure was performed. At 6 months follow-up, there was no episode of cholangitis in first and two episodes in second case. In both patients’ total bilirubin was trending down on follow-up. Cystic biliary atresia presents with cystic dilatation of proximal biliary tract. Type I cystic biliary atresia may masquerade as infantile variant of choledochal cyst. The Kasai portoenterostomy procedure is a standard palliative surgical procedure for patients with biliary atresia to restore bile drainage. A high index of suspicion with early operative intervention is recommended to palliate cholestasis in the infant with cystic variant of biliary atresia.

Neonatal obstructive jaundice is frequently explained by biliary atresia (BA) or the presence of a choledochal cyst (CC). Cystic biliary atresia (CBA) has been a proposed as a subtype of BA with projected improved outcomes. We aimed to characterize these lesions further. We conducted an Institutional Review Board-approved review of all patients treated for obstructive jaundice at our tertiary children's hospital over 10 years. Over the decade we evaluated 91 children with obstructive jaundice: 13 CBA, 52 BA, and 26 CC. Patients with isolated CBA and BA were diagnosed significantly earlier than those with CC (15.9, 54, and 281 days, respectively; P = 0.0001). There was a significant delay between diagnosis and surgical intervention for patients with CBA compared with BA: 17 days versus 5.7 days (P = 0.004). There was no difference in rate of transplant between CBA and BA (31 vs. 50%; P = 0.35). The time from surgery until transplant was 13.9 and 18.6 months for CBA and BA, respectively (P = 0.62). Although radiographically similar to CC, CBA behaves similarly to isolated BA. Delay in recognition and surgical treatment may affect outcomes and lead to an increased incidence of liver failure. The presence of a cystic biliary malformation in the setting of neonatal jaundice should be regarded as CBA until proven otherwise.

The key characteristic of biliary atresia (BA) is obliteration of the extrahepatic bile ducts at the level of the porta hepatis. We aimed to relate the immunohistochemical features of remnant biliary ductules at the porta hepatis with clinical features and outcomes. Samples were immunostained with anti-cytokeratin 20 (CK20), vimentin and alpha-smooth muscle actin (aSMA). Primary outcome was set as clearance of jaundice (bilirubin ≤ 20μmol/L) following Kasai portoenterostomy (KPE). Eighty-two cases were classified into syndromic BA (n = 10), cystic BA (n = 7), CMV IgM+ BA (n = 9) and isolated BA (n = 56). CK20 expression was confirmed in 40/82 (49%), and vimentin expression in 19/82 (23%). aSMA was negative in all cases studied. CK20 expression was less common in isolated BA (n = 20/56, 36%) compared to CMV IgM+ BA (n = 8/9, 89%), cystic BA (n = 7/7, 100%) (isolated BA vs non-isolated BA, P = 0.0008). There was no difference in vimentin expression among the sub-groups (isolated BA vs. non-isolated BA; P = 0.39). CoJ was achieved in 52/82 (63%) overall with significant difference depending simply on sub-group [e.g. syndromic BA 9/10 (90%)]. CK20 expression was associated with a diminished rate of CoJ in the entire cohort [CK20+ 32/56 (57%) vs. CK20- 20/26 (77%); P = 0.04]. By contrast no correlation was observed between vimentin expression and CoJ (P = 0.13). CK20+ expression was associated with reduced clearance of jaundice in BA and a trend towards reduced native liver survival.

Objective To explore the clinical parameters of cystic biliary atresia (CBA) versus choledochal cyst (CC) in neonates or young infants. Methods Retrospective analysis was performed for the clinical data of 96 CBA/CC patients aged under 120 days from January 2013 to November 2015. They were divided into CBA (n=29) and CC (n=67) groups by the findings of intraoperative cholangiography. Two groups were compared with regards to laboratory data, preoperative ultrasonographic features, intraoperative cholangiography and histopathology. CBA group included 9 boys and 20 girls with an operative age of (51.8±24.0) days and a weight of (4.6±0.8) kg; CC group had 20 boys and 47 girls with an operative age of (50.0±26.4) days and a weight of (4.4±1.0) kg. Results The median values of glutamic-pyruvic transaminase (ALT), glutamic-oxalacetic transaminease (AST), total bilirubin (TBil), direct bilirubin (DBil) and total bile acid (TBA) in CBA and CC groups were 59.4 vs 29.5 U/L, 140.1 vs 44.0 U/L, 189.9 vs 87.4 μmol/L, 84.9 vs 14.3 μmol/L and 111.6 vs 8.7 μmol/L respectively. And significant inter-group differences existed in ALT, AST, TBil, DBil and TBA (P<0.001). However, the median gamma-glutamyl transpeptidase (GGT) was 331.9 vs 225.5 U/L. And there were insignificant inter-group statistical differences. The maximal longitudinal and transverse diameters of cyst were (2.5±1.2) and (1.6±0.8) cm in CBA group versus (4.7±2.2) and (3.4±1.8) cm in CC group. And cyst size was obviously smaller in CBA group than that in CC group (P<0.001); in CBA group, small gallbladder (n=4, 13.8%), atrophic gallbladder (n=21, 72.4%), intra-hepatic bile duct dilation (n=6, 20.7%) and triangular cord sign (n=9, 31.0%); in CC group, small gallbladder (n=1, 1.5%), intra-hepatic bile duct dilation (n=29, 43.3%) and none with atrophic gallbladder or triangular cord sign. All preoperative ultrasonographic features had significant inter-group differences (P<0.05 or P<0.001). Histopathological results showed that CBA and CC groups exhibited varying degrees of liver fibrosis and bile duct proliferation. However, the degrees of liver fibrosis and bile duct proliferation were milder in CC group than those in CBA group. Conclusions CBA should be suspected ultrasonically if there are small cysts along with characteristic manifestations of BA and elevated laboratory data. And cholangiography should be performed timely for confirming the diagnosis and surgery scheduled promptly. GGT is an insensitive indicator in distinguishing CBA from CC. Key words: Biliary atresia; Cystic biliary atresia; Choledochal cyst; Clinical parameters

To explore the outcomes and related factors in children without cholangitis after Kasai portoenterostomy (KPE). We retrospectively analyzed the data of infants with type III BA who underwent KPE from June 2016 to December 2021. We compared and analyzed the difference in native liver survival (NLS) rates in different types of cholangitis. We also investigated the relationship between the absence of cholangitis and the effect of early bile drainage (EBD) as well as the related factors affecting EBD efficacy. A total of 145 children were included in this study. Among these children, 82 (56.6%, 82/145) had cholangitis, including 40 (48.8%, 40/82) with early cholangitis and 33 (40.2%, 33/82) with recurrent cholangitis. The median follow-up period was 29 months (range, 2-75 months). The NLS rates were 67.6%, 51.7%, 45.5% and 43.4% at 6 months, 1 year, 2 years and 5 years following KPE, while the NLS rates for infants without cholangitis after KPE were 68.3%, 50.8%, 46.0% and 46.0%, respectively. Higher gamma-glutamyl transferase (γ- GT) and total bile acid (TBA) before KPE were risk factors for cholangitis (P < 0.05). The NLS rate in recurrent cholangitis was significantly lower than that in occasional cholangitis (P < 0.01). Compared with the EBD-poor group, the NLS rate in the EBD-good group of infants was significantly increased (P < 0.001). EBD was significantly correlated with the occurrence and frequency of cholangitis (P < 0.05). Recurrent cholangitis was an important factor affecting NLS. For children without cholangitis after KPE, early bile drainage was better, and the NLS was longer.

The objectives of this study is to compare the prognostic differences between cystic biliary atresia (CBA) and non-CBA, analyze the clinical and liver pathological differences between the two groups, and explore the possible factors that affect the native liver survival of infants with CBA after Kasai portoenterostomy (KPE). From 2013 to 2020, 131 infants with BA were admitted to Tianjin Children's Hospital. A total of 108 infants with BA were included after excluding those who did not undergo surgery after diagnosis (n = 23), including 12 cases of CBA and 96 cases of non-CBA. The clinical data, native liver survival and liver pathology, including liver fibrosis, bile ductular proliferation (BDP), bile plug, and portal area inflammation infiltration of the two study groups were compared. CBA accounts for 9.16% (12/131) and type I CBA accounts for 6.87% (9/131) of all types of BA. 16.7% (2/12) of CBA were detected prenatally with diagnosis of choledochal cyst (CC). The age at KPE, total bilirubin, direct bilirubin, and total bile acid levels of CBA were significantly lower than those of non-CBA (P = 0.047, P = 0.013, P = 0.009, P = 0.010, respectively). The long and wide diameters of the gallbladder were significantly larger than those of non-CBA (both P < 0.001). The 1-, 3-, and 5-year survival rates of CBA were 83.3%, 71.4%, and 71.4%, respectively, and 56.5%, 32.5%, and 29.8%, respectively, in non-CBA. The difference between the two groups was statistically significant (P = 0.031). The degree of liver fibrosis and bile plug in non-CBA was higher than that of CBA (P = 0.004, P < 0.001, respectively). There was no difference of BDP and inflammation infiltration between the two groups (P = 0.285, P = 0.243, respectively). CBA is a distinct type different from non-CBA, with different pathological processes, pathological manifestations, and clinical prognosis. The favorable prognosis of CBA may be derived from the early diagnosis, early operation, and mild pathological changes.

Objective To analyze the impact of etiologic heterogeneity and operative age on short-term outcomes of biliary atresia (BA) undergoing Kasai operation under 60 days.Methods During the period of 2004-2010,a total of 476 BA infants were reviewed.According to the preoperative examinations,4 groups could be defined clinically as cystic BA,syndromic with associated malformations,cytomegalovirus (CMV)-associated and isolated.Results Among them,158 infants underwent Kasai operation under 60 days.There were cystic (n =19),syndromic with associated malformations (n =36),CMV-associated (n =35) and isolated (n =68).The best outcomes were obtained in infants undergoing Kasai operation between 51 to 60 days (62.1％,46/74) while those operated under 40 days had the worse prognosis (42.8％,12/28).Infants with cystic BA had better outcomes than other three groups (68.4％,P＜0.05).Furthermore,this group had favorable prognosis in any operative age.Significant differences existed among the groups of syndromic with malformations (55.9％),CMV-associated BA (57.1％) and isolated BA (52.9％,P＞0.05).Syndromic with malformations group,CMVassociated BA group and those with an early operation (＜40 days) had worse outcomes than those operated between 41-50 days and 51-60 days(P =0.041＜0.05,P =0.029＜0.05).However,in isolated group,infants operated under 40 days had the same outcome with those between 41-50 days (50.0 ％ vs 57.1％,P＞0.05),and also had no significance with those from 51-60 days (50.0％ vs 54.8％,P＞0.05).Conclusions To some extent,operative age has impact on outcome.When Kasai operation is performed under 60 days,infants operated from 51-60 days achieve better outcomes.Clinical etiologic heterogeneity may have prognostic significance. Key words: Biliary atresia; Prognosis; Clinical etiologic

Cystic biliary atresia masquerading as a choledochal cyst

Objective To explore the value of color Doppler ultrasonography (CDU) in the differential diagnosis of cystic biliary atresia (CBA) and choledochal cyst (CC) in infants. Methods A total of 54 infants diagnosed with hepatic portal cystic lesion in the First Affiliated Hospital of Sun Yat-sen University from January 2012 to July 2014 who were going to receive surgical treatment were included in this prospective study. Of the 54 cases, 35 were baby boys and 19 were baby girls with a mean of (63±19) d old. According to the results of pathological examination, the patients were divided into the CBA group and the CC group. All guardians of the infants signed the informed consent and the local ethical committee approval had been received. Preoperative TB level and DB level were recorded. CDU was used to observe the incidence of hepatic portal fibrous mass, intrahepatic bile duct dilation and biliary sludge sedimentation in the cyst. In addition, the length diameter and width diameter of gallbladder and the inner diameter of hepatic artery were measured. The observed parameters of two groups were compared by χ2 test or t test. Results The incidence of hepatic portal fibrous mass in CBA group was 96% (25/26), which was significantly higher than 0 (0/28) in CC group (P<0.05). The incidence of intrahepatic bile duct dilation and biliary sludge sedimentation in the cyst in CBA group were both 0 (0/26), which were significantly lower than 75% (21/28) and 54% (15/28) in CC group (P<0.05). The width diameter of gallbladder in CBA group was (5±1) mm, which was significantly less than (8±2) mm in CC group (t=-38.68, P<0.05). The inner diameter of hepatic artery in CBA group was (2.4±0.4) mm, which was significantly greater than (1.8±0.3) mm in CC group (t=28.40, P<0.05). Conclusions The hepatic portal fibrous mass, intrahepatic bile duct dilation, biliary sludge sedimentation in the cyst, width diameter of gallbladder and inner diameter of hepatic artery are effective indexes for CDU to differentiate CBA and CC, thus, CDU may be used in the preoperative differential diagnosis. Key words: Ultrasonography; Biliary atresia; Choledochal cyst; Jaundice, neonatal

Objective To explore the value of ultrasound in differential diagnosis of hepatic hilar cyst in neonates and infants. Methods The ultrasonographic characteristics of 93 children with hilar cysts under 6 months of age admitted to the General Surgery Department of Beijing Children′s Hospital.Affiliated to Capital Medical University from January 2014 to December 2018 were retrospectively analyzed.According to the surgical results, they were divided into two groups: cystic biliary atresia (CBA) group and congenital choledochal cyst (CC) group, 21 cases in the CBA group and 72 cases in the CC group.The size of cyst in hepatic portal area, the shape of gallbladder in empty stomach, the expansion of intrahepatic and extrahepatic bile ducts, the deposition of biliary sludge and the communication between cyst and intrahepatic bile duct were observed by ultrasound. Results The cyst volume of CBA group was 0.4(0.1, 1.3)cm3, and that of CC group was 18.3(5.4, 50.3)cm3.The cyst volume of CBA group was significantly smaller than that of CC group (P<0.01); 19 cases had abnormal gallbladder morphology in CBA group and 4 cases in CC group (P<0.01); 1 case had biliary sludge in hilar cyst in CBA group and 51 cases had biliary sludge in cyst in CC group (P<0.01); no intrahepatic bile duct dilatation was observed in CBA group, and 54 cases had intrahepatic bile duct dilatation in CC group (P<0.01); no cyst communicated with intrahepatic bile duct in CBA group, and all cysts communicated with intrahepatic bile duct in CC group (P<0.01). Conclusion Gallbladder shape, cyst size, biliary sludge deposition, intrahepatic bile duct dilatation and the communication between cyst and intrahepatic bile duct can be used as sonographic features to differentiate CBA from CC. Key words: Ultrasound; Cystic biliary atresia; Choledochal cyst

BackgroundGood outcomes of biliary atresia (BA) are conventionally achieved after early Kasai portoenterostomy (KP). However, in some recent pieces of literature, there are discrepancies in the influence of age in Kasai procedure on postoperative short-term prognosis. This meta-analysis aims to evaluate the effects of earlier KP on short-term surgical prognosis of BA and clarify these discrepancies in recent studies.MethodsTo identify related studies, PubMed, Embase, Web of Science, Cochrane, and the Chinese National Knowledge Infrastructure database were searched up to March 2022. Data for the impact of age at KP on clinical prognosis were extracted, including jaundice clearance rate (JCR) and native liver survival rate (NLSR).ResultsA total of 14 articles were included in the present study, which involve a total of 3,276 patients with BA who underwent Kasai procedure. Compared with patients older than 91 days of age, patients 90 days of age or younger exhibited significantly better JCR [odds ratio (OR), 3.05; 95% confidence interval (CI), 2.23–4.17; P < .001] and a more favorable NLSR (OR, 1.72; 95% CI, 1.37–2.15; P < .001). The NLSR of patients younger than 60 days of age was significantly higher than those of patients from 61 to 90 days of age (OR, 1.41; 95% CI, 1.18–1.68; P < .001). There was no significant difference in JCRs between patients aged 60 days of age or younger and those aged 61–90 days of age (OR, 1.31; 95% CI, 0.95–1.81; P = 0.10). Among patients 30 days of age or younger, 31–45 days of age, and 46–60 days of age, there were also no significant differences in JCR.ConclusionA significantly better short-term JCR and NLSRs were achieved among patients with BA treated using a KP procedure at ≤90 days of age compared with those treated at >90 days of age. There was no further improvement in the short-term JCR when the procedure was performed at ≤60 days compared with those treated at 61–90 days of age. However, treatment at ≤60 days of age was associated with a significant improvement in NLSR. Therefore, the timing of KP does exert an important effect on short-term clinical outcomes of patients with BA.