Biliary Atresia Patients Research Articles

The effect of APTR, Fn14 and CD133 expressions on liver fibrosis in biliary atresia patients.

Although some biomarkers of hepatic progenitor cells have been reported to be involved in the liver fibrosis in patients with biliary atresia (BA), however, research still shows conflicting results. Therefore, we investigated the effect of Alu-mediated p21 transcriptional regulator (APTR), fibroblast growth factor-inducible 14 (Fn14) and CD133 expressions on liver fibrosis in Indonesian BA patients. Nineteen liver samples from BA patients and 9 liver specimens from non-BA controls were obtained. The expressions of APTR, Fn14 and CD133 were analyzed by quantitative real-time polymerase chain reaction (qPCR). APTR expression was strongly up-regulated (1.5-fold) in liver BA specimens compared to liver controls (ΔCT 3.2 ± 0.6 vs 3.8 ± 0.51; p = 0.028). Moreover, Fn14 and CD133 expressions were similar in the BA and control groups (ΔCT 2.7 ± 1.3 vs. 1.4 ± 1.6, p = 0.07; and 12.0 ± 3.7 vs. 11.78 ± 2.30, p = 0.88, respectively). Intriguingly, CD133 expression was strongly related with the survival of BA patients (p = 0.0061), but not with age at Kasai procedure (p = 0.36) and the presence of cirrhosis (p = 0.77). We present the first study of aberrant APTR expressions in the liver of BA infants which might contribute to liver fibrogenesis in BA infants.

Microvascular proliferation of the portal vein branches in the liver of biliary atresia patients at Kasai operation is associated with a better long-term clinical outcome

We previously showed an increased number of smaller portal vein (PV) branches in the portal areas of liver biopsy specimens of biliary atresia (BA) patients. We evaluated the correlation between this histopathological feature and the prognosis. Twenty-five consecutive patients with BA encountered between 2000 and 2012 were classified into three prognostic groups based on their postoperative outcomes: Excellent (n = 11) for native-liver survivors with a normal liver function, Good (n = 6) for native-liver survivors with liver dysfunction, and Poor (n = 8) for survivors after liver transplant or on a waiting list. Data from morphometrical analyses, including the fibrotic portal area, numbers of PVs, diameter and total area of PV branches, were statistically compared among the three groups. The number of PV branches per unit area of the whole-liver specimen in the poor prognostic group was significantly lower than that in the excellent group (3.1 ± 0.6 vs. 5.2 ± 2.0/mm2, p = 0.03). There were no significant differences in the other parameters. This is the first report on the relationships between morphometrically analyzed PV branches and the postoperative course in BA patients. The portal venous system is involved as the primary lesion in BA.

A multicenter study of primary liver transplantation for biliary atresia in Japan.

Kasai portoenterostomy (KP) is the primary procedure for biliary atresia (BA). However, due to reports of poor outcomes of KP, primary liver transplantation (LT) is preferred in selected cases. In Japan, primary LT is limited with no study reports details, particularly regarding the indications. We conducted the first nationwide survey to assess the status of primary LT in Japan. Questionnaires were sent to institutions where procedures other than KP were performed as the initial procedure for BA and registered to the Japan Biliary Atresia Registry. Parameters related to procedure selection were analyzed. Of 2895 patients registered (1989-2013), primary LT (n = 15) or exploratory laparotomy (EL) followed by LT (n = 9) without KP was performed in 24 cases (0.8%). The main reason for primary LT was late diagnosis, and for EL followed by LT, lack of fibrous tissue at the porta hepatis (ο-type). The prognoses of LT without KP was good. Non-KP initial procedures were limited. Clear criteria regarding the timing of diagnosis or patient condition could not be determined. Reasons for not initially selecting KP varied, but late diagnosis was predominant. Further study is needed to create guidelines for the initial treatment of BA patients.

The outcome of real-time evaluation of biliary flow using near-infrared fluorescence cholangiography with Indocyanine green in biliary atresia surgery

BackgroundIndocyanine green (ICG) fluorescence imaging is a promising tool for intraoperative decision-making. The aim of this study was to evaluate the utility of near-infrared fluorescence cholangiography (NIR-FCG) with ICG in primary surgery for biliary atresia (BA). MethodsWe performed NIR-FCG with ICG in 10 BA patients and observed the fluorescence of their hilar micro-bile ducts and hilar exudate in order to assess the appropriate level at which to dissect the hilar fibrous corn. We compared the jaundice outcome of 10 patients using NIR-FCG (Group A) to that of 35 historical patients in whom NIR-FCG had not been used (Group B). ResultsThe mean age of patients was 74.8 days. The classification of BA was type I in two cases and type-III in eight cases. NIR-FCG visualized the hilar micro-bile ducts, and the incidence of positive fluorescence was 80%. The ratio of postoperative normalization of hyperbilirubinemia in Group A was significantly higher than that in Group B (1.0 vs. 0.65, p < 0.05). ConclusionNIR-FCG provided important objectifiable information about the biliary structures in surgery of BA. Although the number of cases was small, our results suggest that NIR-FCG may be useful for improving the outcome of primary surgery for BA. Type of StudyStudy of Diagnostic Test. Level of EvidenceLevel III.

Risk factors and prognostic effects of cholangitis after Kasai procedure in biliary atresia patients: A retrospective clinical study

PurposeCholangitis after Kasai procedure has been previously shown to be related to poor prognosis in Biliary Atresia (BA). To investigate the risk factors and clinical outcomes of cholangitis, we did a retrospective study in post-Kasai BA patients. MethodsTwo-year follow-up data of 180 type-III BA patients after Kasai procedure in 2016 in our hospital were analyzed, including 119 cholangitis patients (66.11%). Among the cholangitis group, patients were further divided into early vs late cholangitis and single vs recurrent cholangitis groups. Liver pathology, liver function, cholangitis occurrence and frequency, jaundice clearance, and survival rates were examined. ResultsHigher gamma-glutamyl transferase level before Kasai is a risk factor for cholangitis (p = 0.0393). Older age and higher liver fibrosis score at Kasai are risk factors for recurrent cholangitis (p < 0.05). Shorter prophylactic intravenous antibiotics usage may contribute to early cholangitis, which may lead to higher cholangitis frequency (p < 0.0001). Recurrent cholangitis is associated with earlier cholangitis onsets (p < 0.0001). Cholangitis patients have a relatively delayed jaundice clearance, while early and recurrent cholangitis may contribute to lower overall survival. ConclusionsPersonalized treatment considering risk factors in individual BA patients is needed to prevent cholangitis, especially early onsets, and to improve postoperative outcomes. Level of evidenceIII

Serum Mac-2-binding protein (M2BPGi) as a marker of chronological liver fibrosis in biliary atresia patients with cirrhosis.

Biliary atresia (BA) is characterized by progressive liver fibrosis, but it is difficult to assess the progression after the patient develops cirrhosis. Mac-2-binding protein glycosylation isomer (M2BPGi) is a new marker for hepatic fibrosis. We examined the chronological changes in M2BPGi levels in BA patients with cirrhosis. Patients with cirrhosis were selected from among pediatric BA patients who had their native livers. Serum M2BPGi levels and Child-Pugh classification were evaluated. A total of 11 pediatric BA patients with cirrhosis were recruited. Initial M2BPGi level after diagnosis of liver cirrhosis based on liver biopsy was on average 3.4, and the most recent M2BPGi level under observation was on average 4.3. The follow-up period from the initial M2BPGi measurement averaged 22.6months. The ratio of the initial and most recent values (M2BPGi ratio) was on average 1.3 (0.5-2.4). Three cases with improved fibrosis (M2BPGi ratio < 1.0) remained in Child A, as did six cases (1.0 ≤ M2BPGi ratio < 2.0), but two cases with marked fibrosis progression (2.0 ≤ M2BPGi ratio) advanced to decompensated cirrhosis Child B. M2BPGi is useful as a prognostic factor for BA patients with liver cirrhosis. In addition, fibrosis improved even after the development of cirrhosis.

Gut microbial profile in biliary atresia: a case‐control study

Biliary atresia (BA) is a progressive fibro-inflammatory cholangiopathy with an unclear etiology. Various liver disorders are associated with an altered microbiome. However, gut microbiome in BA remains unknown. Here, we performed a case-control study to investigate the gut microbiota in BA. A cross-sectional analysis was first conducted for 34 BA patients and 34 healthy controls. Then we investigated the shift in gut microbiota 2weeks after the Kasai procedure in 16 BA patients. Gut microbiome was initially analyzed using 16S ribosome RNA gene sequencing and further validated by metagenomic sequencing. Fecal bile acids were determined using ultra-high performance liquid chromatography. Compared with healthy controls, BA showed lower diversity and significant structural segregation in the microbiome. At phylum level, Proteobacteria numbers increased, whereas those of Bacteroidetes decreased in BA. At genus level, several potential pathogens such as Streptococcus and Klebsiella thrived in BA, while numbers for Bifidobacterium and several butyrate-producing bacteria declined. The microbiome was also disturbed after the Kasai procedure. Operational taxonomic units responding to BA showed significant correlation with liver function. Furthermore, the abundance ratio of Streptococcus/Bacteroides showed great promise in distinguishing BA from healthy controls. Intestinal bile acids were dramatically decreased in BA, and Clostridium XIVa positively correlated with the ratio of primary/secondary bile acids. Gut microbial dysbiosis, may be caused by decreased bile acids, was associated with liver function and had a good diagnostic potential for BA. Therefore, further exploration of gut microbiota may provide important insights into their potential diagnostic and therapeutic benefits.

Quantitative Contrast-Enhanced Ultrasound by Sonazoid in the Early Diagnosis of Biliary Atresia: An Experimental Study of Rats With Bile Duct Ligation

We aimed to investigate the feasibility of quantitative Sonazoid contrast-enhanced ultrasound (CEUS) in the diagnosis of biliary atresia (BA) at an early disease stage. First, liver tissue from 10 patients with BA and 10 patients with infantile hepatitis syndrome (IHS) was immunostained with cluster of differentiation 68 (CD68) to compare Kupffer cell counts. Then, quantitative Sonazoid CEUS was performed to evaluate the hyperplasia of the artery branches during the artery phase and changes in Kupffer cell counts during the Kupffer phase in a rat model of BA (common bile duct ligation). Based on our results, liver enhancement from Kupffer cells in BA patients was significantly higher than that in IHS patients (p = 0.026 < 0.05). Furthermore, quantitative CEUS showed that the liver enhancement intensity of rats with bile duct ligation was substantially greater than that of rats without bile duct ligation during the artery phase 3 d post-operation and the Kupffer phase 5 d post-operation. The increased enhancement intensity in the Kupffer phase was in agreement with the increase in Kupffer cell counts in pathologic staining (18/20, 90%). In conclusion, quantitative Sonazoid CEUS can detect the hyperplasia of artery branches in artery phase and the increase of Kupffer cells in Kupffer phase in the liver of BA rats at an early disease stage. Therefore, Sonazoid CEUS could potentially be a valuable non-invasive alternative for the diagnosis of BA.

CD4+T Cell Subset Profiling in Biliary Atresia Reveals ICOS- Regulatory T Cells as a Favorable Prognostic Factor.

Biliary atresia (BA) is a destructive pediatric liver disease and CD4+T cell activation is demonstrated to play an important role in BA. However, a comprehensive scenario regarding the involvement of CD4+T cell subsets to the development of BA remains unclear. Here, we aim to explore the infiltration of CD4+T cell subsets and their clinical significance in BA. In the present study, thirty BA liver samples were collected during surgery and were divided into good (BA1, n = 16) and poor prognosis (BA2, n = 14), with samples from choledochal cyst patients (n = 8) as control. By using multiplex immunohistochemistry, we evaluated the infiltration level of CD4+T cell subsets in the portal areas. RT-qPCR and flow cytometry were further applied to explore detailed features of Treg subsets. We revealed that hepatic infiltrating Th1, Th2, Th17, and ICOS+Treg cells were significantly increased in BA patients compared to controls and were negatively associated with prognosis, while high infiltrating ICOS−Tregs showed a favorable outcome. Phenotypic analysis indicated that, in contrast to ICOS+Tregs, ICOS−Tregs were mainly CD45RAhiCD45ROlow, and preferentially expressed more CD73. Besides, RT-qPCR revealed elevated expression of CD25, CD73, TGF-β, and BCL-2 genes in ICOS−Tregs. Finally, functional assay confirmed that ICOS−Tregs had a higher suppressive capacity to cytokine secretion and were more resistant to apoptosis in vitro. Collectively, we demonstrate that a mixed immune response is involved in BA pathogenesis, and the globally enhanced effector CD4+T cell response is associated with unfavorable prognosis, highly suppressive ICOS−Tregs is a protective factor and may serve an important reference to predict prognosis.

Predictors of demand for liver transplantation in children undergoing Kasai portoenterostomy for biliary atresia

Context Biliary atresia (BA) remains the most common indication for pediatric liver transplantation worldwide. Ultimately, 50–80% of BA patients will require a liver transplant Thus, much of the research in the field has focused on identifying predictors for transplant and optimizing the efficacy of Kasai portoenterostomy (KPE), in order to decrease the need for transplantation and avoid the risks of lifelong immunosuppression. Aim The aim of this study was to identify perioperative risk factors for the need of liver transplantation following KPE operation for BA. Patients and methods A retrospective analysis of 150 patients undergoing KPE for BA at Hepatobiliary and Pancreatic Surgery Department, National Liver Institute, Menoufia University, from May 2013 to May 2018, was carried out. Patients were divided into two groups: group one included 73 (48.7%) patients who survived without the need for liver transplantation and group two included 77 (51.3%) patients with mortality, listed for liver transplantation or transplanted; thereafter, logistic regression analysis was used to identify the independent predictors of cases needing liver transplantation. Statistical analysis used Continuous variables were expressed as mean±SD and categorical variables as proportions. Univariate analysis for the two groups were carried out using the independent samples t test for continuous variables and χ2 test for categorical variables. Logistic regression analysis was used to identify the independent predictors of cases needing liver transplantation. Receiver operating characteristic analysis was used for the cut-off determination of predictive parameters using MedCalc application, version 18.2.1. Results The mean age at the time of operation was 74.9±14.6 days after birth (range, 31–111 days); there were 70 (46.7%) male babies and 80 (53.3%) female babies. The mean preoperative weight was 4.6±0.6 kg, while the mean preoperative height was 57.3±3.58 cm. Total bilirubin and albumin levels at 1 and 3 months following KPE were associated with death or the need for liver transplantation; however, only a total bilirubin level of more than 6 mg/dl at 3 months is an independent predictor of the need for liver transplantation. Age at the time of KPE and postoperative steroid use were not associated with improved transplant-free survival. Conclusion Total bilirubin level of more than 7.3 mg/dl at 1 month and a level of more than 6 mg/dl at 3 months after KPE are predictive of the need for liver transplantation (P

Serum vitamin D level is inversely associated with liver fibrosis in post Kasai's portoenterostomy biliary atresia patients living with native liver.

ObjectiveThis study aims to investigate the association of serum vitamin D (VD) levels with the severity of liver fibrosis (LF) in post Kasai’s portoenterostomy biliary atresia (PKBA) patients living with their native liver.MethodsIn this cross-sectional study, carried out in a tertiary Children’s Hospital in Taipei, Taiwan, PKBA patients living with their native liver were enrolled. Liver biochemistry data, serum 25-hydroxyvitamin D (25-OHVD), acoustic radiation force impulse (ARFI), and scores of Pediatric Quality of Life questionnaire (PedsQL) were collected.ResultsAll the enrolled 33 PKBA patients (36.4% males), aged 1–23 years, possessed 25-OHVD less than 30ng/ml. An inverse correlation was detected between serum 25-OHVD and ARFI (r2 = 0.175; p = 0.024). We selected a cutoff value of 23ng/mL to divide PKBA patients into two groups, as the p-value was the most significant at this point when comparing the median ARFI of two groups (p = 0.003). Ten (30.3%) had 25-OHVD≥23ng/ml (HVD group), whereas 23(69.7%) had 25-OHVD<23ng/ml (LVD group). HVD group had lower ARFI (1.13m/s vs. 1.52m/s, p = 0.003), lower aspartate transaminase (AST) (29U/L vs. 64U/L, p = 0.033), and higher scores of self-reported health-related quality of life in psychosocial functioning (86.7 vs. 77.1, p = 0.047) than LVD group.ConclusionVD levels are inversely associated with severity of LF in PKBA patients with native liver.

Perioperative Complications after Kasai Hepatoportoenterostomy: Data from the Swiss National Biliary Atresia Registry.

Hepatoportoenterostomy (HPE) is the first-line treatment for biliary atresia (BA) patients. This study aims to describe perioperative complications after HPE and to analyze their impact on outcome. Patients with HPE (Swiss National Biliary Atresia Registry, 1994-2017) were retrospectively analyzed. Perioperative complications were defined as complications occurring up to 30 days after surgery. Surgical complications were defined as directly related to the surgical act; medical complications were defined as any other deviation from the uneventful postoperative course. Sixty-two patients were included. Median age at HPE was 63 days (18-126). Twenty six patients out of 62 (42%) had ≥ 1 complications: 6/62 (10%) surgical, 24/62 (39%) medical, that is, we observed 7 surgical and 28 medical complications. As for medical complications, cholangitis was the most frequent: 19/28 (68%). Lower gestational age at birth correlated with more overall complications (p = 0.02). Age, weight at HPE, syndromic BA, and postoperative steroid administration were not significantly correlated. There were no perioperative deaths. Perioperative complications did not correlate with overall survival (p = 0.14) and survival with native liver (p = 0.55). HPE is often associated with perioperative medical complications. Lower gestational age at birth was significantly associated with more complications. Perioperative complications had no impact on overall outcome.

Long Noncoding RNA H19 Contributes to Cholangiocyte Proliferation and Cholestatic Liver Fibrosis in Biliary Atresia.

Biliary atresia (BA) is a neonatal liver disease featuring cholestasis and severe liver fibrosis (LF). Despite advances in the development of surgical treatment, lacking an early diagnostic marker and intervention of LF invariably leads to death from end-stage liver disease in the early years of life. We previously reported that knockout of sphingosine 1-phosphate receptor 2 (S1PR2) protected mice from bile duct ligation (BDL)-induced cholangiocyte proliferation and LF. Our recent studies further showed that both hepatic and serum exosomal long noncoding RNA H19 (lncRNAH19) levels are correlated with cholestatic injury in multidrug resistance 2 knockout (Mdr2-/- ) mice. However, the role of lncRNAH19 in BA progression remains unclear. Here, we show that both hepatic and serum exosomal H19 levels are positively correlated with severity of fibrotic liver injuries in BA patients. H19 deficiency protects mice from BDL-induced cholangiocyte proliferation and LF by inhibiting bile-acid-induced expression and activation of S1PR2 and sphingosine kinase 2 (SphK2). Furthermore, H19acts as a molecular sponge for members of the microRNA let-7 family, which results in up-regulation of high-mobility group AT-hook 2 (HMGA2), a known target of let-7 and enhancement of biliary proliferation. Conclusion: These results indicate that H19 plays a critical role in cholangiocyte proliferation and cholestatic liver injury in BA by regulating the S1PR2/SphK2 and let-7/HMGA2 axis. Serum exosomal H19 may represent a noninvasive diagnostic biomarker and potential therapeutic target for BA.

Health-Related Quality of Life in Patients with Biliary Atresia: A Systematic Review and Meta-Analysis

Objectives: In this systematic review and meta-analysis, for the first time, the existing evidence on health-related quality of life (HRQOL) was evaluated in patients with biliary atresia (BA) and compared with that of healthy population. Methods: A systematic search was done on PubMed, Scopus, Embase, Cochrane Library and Web of Science from 1990 up to April 2018 in order to identify all articles that assess the HRQOL in patients with BA. Meta-analysis was done using comprehensive meta-analysis and the standard difference of mean (SDM) was calculated. Results: A total of 188 publications were identified from the initial search. After removing duplicates and irrelevant studies, 32 articles remained for full-text evaluation. Out of this number, 22 articles were excluded due to non-relevance to the study scope leaving 10 studies for systematic review and three articles for meta-analysis. HRQOL was assessed using PedsQL4 in three studies, SF-36C in two studies and by assessing different parameters including social status, school, university, and/or sports performance in five studies. HRQOL in BA patients living with their own liver was significantly lower than that of the general population [SDM = -0.55 (95% CI: -0.69, -0.40)]. In the terms of PedsQL4 sub-scores, compared with healthy population, the levels of physical [SDM = -0.40 (95% CI: -0.55, -0.28)], social [SDM = -0.25 (95% CI: -0.40, -0.11)] and school functioning [SDM = -1.19 (95% CI: -2.35, 0.07)] were significantly lower in the group of biliary atresia.

Leukocyte mitochondrial DNA copy number as a potential biomarker indicating poor outcome in biliary atresia and its association with oxidative DNA damage and telomere length

Biliary atresia (BA) is a chronic obstructive liver disease, leading to advanced liver failure. Mitochondria dysfunction-mediated aberrant telomere length has been implicated in various pathological processes including cholestasis. Herein, we aimed to investigate associations between mitochondrial DNA (mtDNA) copy number, oxidative DNA damage, telomere length, and disease severity in BA patients. mtDNA copy number and relative telomere length (RTL) were assessed using real-time PCR. Circulating 8-hydroxy-2′-deoxyguanosine (8-OHdG) was measured using ELISA. Our findings showed that BA patients had significantly lower mtDNA copy number and RTL than healthy controls, whereas plasma 8-OHdG levels were significantly elevated in BA patients. mtDNA copy number was remarkably reduced in advanced BA patients. Furthermore, mtDNA copy number was independently associated with age and degree of liver fibrosis in BA patients. Decreased mtDNA copy number was significantly associated with elevated risks of BA, severe fibrosis, jaundice, and hepatic dysfunction. Low mtDNA copy number can be utilized to distinguish patients with poor-outcome from those with good-outcome. Survival curve analysis revealed that low mtDNA copy number was significantly associated with poor survival of BA patients. Interestingly, there was a positive association between mtDNA copy number and plasma 8-OHdG in BA patients, while a negative association of mtDNA copy number with RTL was observed in BA patients. Alternatively, RTL was negatively correlated with plasma 8-OHdG in BA patients. These data demonstrated relationships between leukocytes mtDNA copy number, oxidative stress, telomere length, and clinical parameters in BA patients. Accordingly, our findings indicate that mtDNA copy number may serve as a potential biomarker reflecting BA severity.

Correlation between hepatic oxidative damage and clinical severity and mitochondrial gene sequencing results in biliary atresia

To assess the level of hepatic oxidative damage and its correlation with clinical severity in biliary atresia (BA), and to understand BA mitochondrial gene sequencing. Forty-eight BA patients and 28 control subjects (20 hepatoblastoma and 8 cholestasis patients) were enrolled. Hepatic oxidative damage was assessed by the expression of oxidation and antioxidant genes, and the correlation between oxidative damage and BA incidence, liver inflammation, and fibrosis was evaluated. Moreover, 8-hydroxyguanine (8-OHdG), mitochondrial DNA (mtDNA) copy number, and mitochondrial gene sequences were determined to evaluate oxidative mtDNA damage in BA. The expression of oxidation gene cytochrome b-245 beta chain (CYBB) in BA was significantly increased and patients with a higher CYBB expression had the higher risk of BA incidence, liver inflammation, and cirrhosis. However, the expression of antioxidant genes was significantly decreased, and glutathione S-transferase alpha 1 (GSTA1) negatively correlated with BA incidence and cirrhosis. When GSTA1 mRNA expression was <0.5487, the sensitivity was 80.85% and the specificity was 80% for BA diagnosis. Moreover, 8-OHdG was increased, whereas mtDNA copy number was significantly decreased in BA. Using mitochondrial gene sequencing, 10 mutation sites were identified, and one family showed a maternal inheritance in genetic loci 15 326. In BA, oxidative damage positively correlated with BA incidence, liver inflammation, and cirrhosis. GSTA1 could be a novel diagnostic indicator. Genetic loci 15 326 could be a maternal genetic mutation site. Taken together, antioxidation therapy after Kasai surgery might have great potential in relieving liver inflammation and fibrosis in BA patients.

Genetics in biliary atresia.

Biliary atresia is a poorly understood deadly disease. Genetic predisposition factors are suspected albeit not firmly established. This review summarizes recent evidence of genetic alterations in biliary atresia. Whole-genome association studies in biliary atresia patients identified four distinct predisposition loci with four different genes potentially involved in the disease occurrence. Variations in these genes were searched for, but none were found in patients with biliary atresia suggesting complex mechanisms. Despite decades since its description and decades of intensive researches, cause of biliary atresia disease remains enigmatic. The inheritance of biliary atresia is not Mendelian. Genetic predisposition factor is one of the explored fields to explain biliary atresia pathogenicity. Biliary atresia has been associated with several inborn syndromes, chromosome anomalies, and gene polymorphisms in specific populations. Four predisposition loci encompassing genes relevant to the disease have been identified, but no pathogenic variations were found in biliary atresia patients. Few reported cases of isolated biliary atresia manifestation in the context of known genetic diseases suggest coincidental findings. Alternatives to classic genetic alterations are proposed to explain genetic predisposition in biliary atresia including noncoding and epigenetic factors. Biliary atresia is most likely related to complex traits making its genetic exploration challenging.

MULTIVARIATE ANALYSIS OF BILIARY FLOW-RELATED FACTORS AND POST-KASAI SURVIVAL IN BILIARY ATRESIA PATIENTS.

Biliary atresia represents the most common surgically treatable cause of cholestasis in newborns. If not corrected, secondary biliary cirrhosis invariably results. To evaluate, through multivariate analysis, the prognostic factors associated with the presence of biliary flow and survival with the native liver following Kasai portoenterostomy. The study analyzed data from 117 biliary atresia patients who underwent portoenterostomy and had suitable histological material for evaluation. A logistic regression model was used to assess the presence of biliary flow. Survival was investigated through Kaplan-Meier curves and Cox-adjusted models. One third of patients achieved biliary flow and the median age at surgery was 81 days. Age at surgery, albumin, postoperative complications, biliary atresia structural malformation (BASM), liver architecture, larger duct diameter at porta hepatis, and cirrhosis (Ishak score) were the initial variables for the multivariate analysis. Age at surgery >90 days was the only variable associated with the absence of biliary drainage. Survival analysis revealed that the absence of biliary flow (P<0.0001), age at surgery >90 days (P=0.035), and the presence of BASM (P<0.0001), alone, could predict death or need for liver transplantation. Multivariate analysis demonstrated that the absence of biliary flow (P<0.0001 hazard ratio [HR] 6.25, 95% confidence interval [CI] 3.19-12.22) and the presence of BASM (P=0.014 HR 2.16, 95% CI 1.17-3.99) were associated with lowest survival with the native liver. Age at surgery >90 days was associated with absence of biliary flow. The presence of biliary drainage and the absence of structural malformations are cornerstone features for higher survival rates with the native liver.

Applycation of laparoscopy in the diagnosis and treatment of obstructive infantile cholestasis

Objective To study the use of laparoscopy in the diagnosis and treatment of obstructive infantile cholestasis. Methods The clinical data of 106 patients with obstructive infantile cholestasis from January 2012 to June 2017 were studied retrospectively. After two weeks of conservative treatments which failed to decrease the bilirubin levels significantly, these patients were subjected to laparoscopic diagnosis and treatment. Results A correct diagnosis was established in all these 106 patients by laparoscopic biliary tract exploration and cholangiography. Eighty-eight patients were diagnosed to have biliary atresia (83.0%), 16 patients inspissated bile syndrome (15.1%) and 2 patients biliary hypoplasia (1.9%). Thirty-eight of the 88 biliary atresia patients gave up operative treatment after laparoscopic biliary tract exploration and cholangiography. The remaining 50 biliary atresia patients were treated with open Kasai portoenterostomy. The prognosis of the biliary atresia patients were different from the non-biliary atresia patients. On follow-up for 4 months to 5 years, all the 18 non-biliary atresia patients were in good condition and there was no recurrence of jaundice after laparoscopic cholecystostomy and biliary tract irrigation. Conclusions The laparoscopic minimally invasive technique helped to establish diagnosis and treatment in patients with obstructive infantile cholestasis. For patients with biliary atresia, this procedure gave a definitive diagnosis and offered an opportunity for surgery. For patients with inspissated bile syndrome and biliary hypoplasia patients, laparoscopic cholecystostomy and biliary tract irrigation established the correct diagnosis and reduced liver damage resulted by cholestasis. Key words: Laparoscopy; Biliary tract surgical procedure; Biliary tract diseases; Biliary atresia; Infant, newborn, disease

A retrospective study of the ideal operation time for preterm biliary atresia patients.

To study the ideal Kasai portoenterostomy (KPE) time for preterm infants with biliary atresia (BA) through evaluation of the postoperative effects. Retrospectively, 34 preterm infants with BA from 2012 to 2016 were recruited in the present study. The following three groups were established according to their chronological and corrected age at the time of KPE operation: chronological age ≤ 90days, chronological age > 90days and corrected age ≤ 90days, and corrected age > 90days. For chronological age ≤ 90days at operation, patients were further divided into another three groups: chronological age ≤ 60days, chronological age > 60days and corrected age ≤ 60days, and corrected age > 60days. Postoperative effects were then followed up and recorded. First, of those patients divided according to 90-day chronological and corrected age, postoperative total bilirubin levels (TBL), direct bilirubin levels (DBL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) of the group whose chronological age was ≤ 90days were lower than the levels of the group whose chronological age was > 90days and corrected age ≤ 90days (P = 0.0472, P = 0.0358, P = 0.0083, and P = 0.0491), and the group whose corrected age was > 90 days (P = 0.0383, P = 0.0392, P = 0.0043, and P = 0.0107). Second, for those patients whose chronological age was ≤ 90 days, the group whose corrected age was > 60 days showed a higher ALT level than the other two groups with chronological age ≤ 60 days (P = 0.0472) and chronological age > 60 days and corrected age ≤ 60 days (P = 0.0258). According to the present study, the ideal KPE time for preterm BA infants should meet two conditions: chronological age ≤ 90days and corrected age ≤ 60days. The groups with a chronological age ≤ 60days, and chronological age > 60days and corrected age ≤ 60days show similar postoperative effects.