The Assessment and Management of Biliary Atresia in Hawai'i, 2009-2023.

Although biliary atresia (BA) is a rare neonatal disorder, it remains the leading cause of pediatric end-stage liver disease. Early diagnosis of BA and treatment with the Kasai procedure can significantly reduce the need for pediatric liver transplant. Current data suggests that performing the Kasai procedure at 30-45 days of life is associated with longer native liver survival rates and reduction of the need for liver transplant. The incidence rate of BA in the state of Hawai'i is nearly double the incidence rate in the continental US. International studies have demonstrated that screening programs for BA reduce the age at diagnosis and treatment. However, there has been no statewide analysis on the ages at diagnosis or at Kasai, nor does a statewide screening program for BA exist. The purpose of this study is to review the age of diagnosis and treatment of BA to determine if the current practice in Hawai'i is in line with the published data. A retrospective chart review of all patients diagnosed with BA at the state's primary children's hospital was performed (2009-2023) and 19 patients who underwent the Kasai procedure were identified. The mean age at diagnosis is 71.4 days (n=19) and the mean age at Kasai procedure is 72.0 days (n=19). Both the average age at diagnosis and treatment for BA in Hawai'i is significantly higher than published data suggesting best outcomes at 30-45 days of life. This review suggests that the implementation of a statewide screening program for BA in Hawai'i is warranted.

Timing of Kasai Procedure for Biliary Atresia: An Analysis of the Pediatric National Surgical Quality Improvement Program Database.

INTRODUCTION: Biliary atresia is a rare liver disease of unknown etiology affecting approximately 1 in 10,000 children. This disease initially presents as inflammatory obstruction of bile ducts leading to cholestasis and eventually fibrosis of hepatic tissue. Affected patients are ideally treated early with portoenterostomy (Kasai procedure) as age at surgery is an important prognostic factor for native liver survival and need for liver transplant. This study aimed to evaluate the age at which patients in the United States are receiving this procedure. METHODS: The American College of Surgeons National Surgical Quality Improvement Program Pediatric database was used to identify patients between 2012 and 2021 who underwent a primary procedure of portoenterostomy. The age at time of surgery and perioperative analysis was performed. The data underwent simple descriptive statistics. RESULTS: Eight hundred twenty four patients were identified who underwent Kasai procedure. Four hundred seventy four (58.2%) were female with the predominant race being White (49.5%). The median age at surgery was 57 d old (interquartile range 41-71). Readmission and reoperation rates within 30 d were 30% and 15.2%, respectively. There were no deaths within 30 d. CONCLUSIONS: Within the National Surgical Quality Improvement Program database, the median age of pediatric patients undergoing Kasai procedure for biliary atresia in the United States exceeds the goal of 45 d. Further studies are needed to investigate factors that may affect time to diagnosis and time to Kasai procedure.

Biliary Atresia Associated With Jejunal Atresia: A Case Report.

A girl who was born at 40 weeks of gestation weighing 3800 g presented with bilious vomiting and abdominal distension shortly after birth. A lower gastrointestinal contrast study showed a microcolon with small bowel atresia. Subsequently, laparotomy, small bowel resection and anastomosis were done. Intra-operative findings noted jejunal atresia type 3a. Post-operatively, the patient developed persistent conjugated hyperbilirubinaemia and hence, magnetic resonance cholangiopancreatography (MRCP) was performed. MRCP revealed possible biliary atresia (BA) of which the patient underwent Kasai hepato-porto-enterostomy. We reported a rare case of double pathology involving jejunal atresia and BA, describing its aetiology, characteristics and treatment availability based on literature.

Use of stool color card as screening tool for biliary atresia in resource-constraint country.

Aim: The study was aimed to find out the efficacy of a stool color card (SCC) in differentiating biliary atresia (BA) from non-BA in resource-limited countries. Background: stool color screening system was introduced in 2004 which lead to marked improvement in sensitivity of detecting BA. Methods: This cross-sectional observational study was conducted from January, 2019 through July, 2022 on purposively sampled infants who developed jaundice before three months of age, had direct bilirubin of > 20 % of total with pale stool and dark urine. Results: 144 cases (male, 96) were included in the study and their mean age at admission was 87.3±37.2 days and mean age at onset of jaundice was 6.1±7.7 days. BA was confirmed in 106 (73.6%) cases and 38 (26.4%) children were in non-BA group. Frequency of persistent pale stool between BA and non- BA were 88 vs 8 (83.0 % Vs 21.0 %) which was highly significant (p=0.000). Mean difference of total and direct serum bilirubin, median alanine transferase and alkaline phosphatase were not statistically significant between two groups. Median of serum gamma glutamyl transpeptidase (GGT) in BA was 570 U/L and in non-BA it was 138.0 U/L which was statistically significant (p=0.000). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of SCC were 83%, 78.9%, 91.7%, 62.5% and 81.9% respectively. Conclusion: SCC has good sensitivity to diagnose BA but failed to prove better specificity to rely simply on it. SCC may be used as early screening tool for prompt referral to appropriate medical care centers for final evaluation of BA.

Effect of Kasai procedure on liver transplantation in children with biliary atresia: a systematic review and updated meta-analysis.

Background: Kasai procedure and liver transplantation are effective ways to save the life of children with biliary atresia (BA). However, with the gradual development of liver transplantation technology, scholars have questioned the necessity of the Kasai procedure. Therefore, we conducted a meta-analysis to evaluate the effect of previous Kasai procedures on liver transplantation in children with BA. Methods: Seven databases were searched and screened from the establishment of the database to May 3, 2023. The data in the included literature were extracted for meta-analysis to compare the differences between the Kasai group and the non-Kasai group. Finally, a publication bias test, sensitivity analysis, subgroup analysis, and systematic review were performed. Results: A total of 26 studies were included in which 6,522 children with BA underwent liver transplantation, including 4,989 in the Kasai group. Compared with the non-Kasai group, the Kasai group had older age [standardized mean difference (SMD) =0.64; 95% confidence interval (CI): 0.46, 0.82; P<0.001] (I2=78.6%), heavier weight (SMD =0.41; 95% CI: 0.33, 0.48; P<0.001) (after sensitivity analysis, I2=0.0%), lower pediatric end-stage liver disease (PELD) (SMD =-0.41; 95% CI: -0.48, -0.35; P<0.001) (I2=20.1%), longer operation time (SMD =0.33; 95% CI: 0.01, 0.65; P<0.001) (I2=83.2%), more intraoperative blood loss (SMD =0.26; 95% CI: 0.06, 0.46; P=0.012) (I2=19.1%), shorter intensive care unit (ICU) stay (SMD =-0.09; 95% CI: -0.34, 0.15; P=0.027) (I2=68.6%) and higher incidence of intestinal perforation [odds ratio (OR) =1.96; 95% CI: 1.20, 3.18; P=0.007] (I2=7.4%) and biliary complications (OR =1.41; 95% CI: 1.05, 1.89; P=0.024) (I2=31.4%). In the "Asia" subgroup, the Kasai group was older (SMD =0.68; 95% CI: 0.52, 0.84; P<0.001) (I2=28.2%). In the "Cases since 2000" subgroup, there was no significant difference in operation time between the two groups (I2=28.5%). In the "Other" and the "non-Asia" subgroup, there was no significant difference in length of intensive care unit (ICU) stay between the two groups (I2=0.0%). However, there were no significant differences in other postoperative complications and prognostic indicators between the two groups. Conclusions: For children with BA undergoing liver transplantation, although previous Kasai procedure may increase the risk of intraoperative bleeding, biliary complications, and intestinal perforation, it does not affect the main clinical outcomes, and can even delay the timing of liver transplantation and improve the preoperative status of children. Therefore, when BA children have no obvious contraindications to Kasai procedure, the sequential treatment of Kasai procedure-liver transplantation should be supported first.

A convenient nomogram for predicting early death or liver transplantation after the Kasai procedure in patients with biliary atresia.

PURPOSE: Many patients with biliary atresia (BA) after the Kasai procedure (KP) progress to death or require liver transplantation to achieve long-term survival; however, most cases of death/liver transplantation (D/LT) occur in the early period after KP (usually within 1 year). This study was designed to construct a convenient nomogram for predicting early D/LT in patients with BA after KP. METHODS: A BA cohort was established in May 2017, and up to May 2023, 112 patients with 1-5 years of follow-up were enrolled in the study and randomly (ratio, 3:1) divided into a training cohort for constructing a nomogram (n = 84) and a validation cohort (n = 28) for externally validating the discrimination and calibration. The training cohort was divided into two groups: the early D/LT group (patients who died or had undergone LT within 1 year after KP [n = 35]) and the control group (patients who survived through the native liver more than 1 year after KP [n = 49]). Multivariate logistic regression and stepwise regression were applied to detect variables with the best predictive ability for the construction of the nomogram. The discrimination and calibration of the nomogram were internally and externally validated. RESULTS: The Kaplan-Meier (K-M) curve showed an actual 1-year native liver transplantation (NLS) rate of 57.1% and an estimated 2-year NLS rate of 55.2%. By multivariate regression and stepwise regression, age at KP, jaundice clearance (JC) speed 1 month after KP, early-onset PC (initial time < 36.5 days) after KP, sex, aspartate aminotransferase-to-platelet ratio index (APRI), and weight at KP were identified as the independent variables with the best ability to predict early D/LT and were used to construct a nomogram. The developed nomogram based on these independent variables showed relatively good discrimination and calibration according to internal and external validation. CONCLUSION: Most D/LTs were early D/LTs that occurred within 1 year after KP. The established nomogram based on predictors, including sex, weight at the KP, the APRI, age at the KP, JC speed 1 month after the KP, and early PC, may be useful for predicting early D/LT and may be helpful for counseling BA patients about patient prognosis after KP. This study was retrospectively registered at ClinicalTrials.gov (NCT05909033) in June 2023.

Collagen gene cluster expression and liver fibrogenesis in patients with biliary atresia: a preliminary study.

OBJECTIVE: Biliary atresia (BA) is a progressive fibro-obliterative disease of the biliary tract, which results in end-stage liver disease. However, liver fibrosis progression may continue even after Kasai surgery. Recent evidence showed that collagen plays a pivotal role in the progression of liver fibrosis in BA. However, most studies were conducted in developed countries. We investigated the expressions of the collagen gene cluster (COL6A1, COL6A2, COL6A3, and COL1A1) in BA patients in Indonesia. RESULTS: There was a significant down-regulated expression of COL6A1 (ΔCT 9.06 ± 2.64 vs. 5.42 ± 2.41; p = 0.0009), COL6A2 (ΔCT 8.25 ± 2.07 vs. 5.77 ± 3.51; p = 0.02), COL6A3 (ΔCT 11.2 ± 6.08 vs. 6.78 ± 3.51; p = 0.024), and COL1A1 (ΔCT 3.26 ± 1.71 vs. 0.19 ± 2.76; p = 0.0015) in BA patients compared to controls. Interestingly, the collagen gene cluster expressions were significantly associated with the presence of cirrhosis (p = 0.0085, 0.04, and 0.0283 for COL6A1, COL6A2, and COL6A3, respectively). In conclusion, our study shows the changes in the collagen gene cluster, particularly collagen type I and VI, expressions in patients with BA in a particular developing country. Our findings suggest the role of these collagen gene clusters in the liver fibrogenesis of BA.

Development and post-Kasai procedure prognostic relevance of histological features for biliary atresia.

OBJECTIVES: To validate an appropriate evaluation method of liver fibrosis assessment based on the unique pathological features of biliary atresia (BA) that could well predict its prognosis. METHODS: A total of 68 patients with BA who underwent Kasai procedure (KP) and an intraoperative liver biopsy, followed up from January 2019 to December 2021, were recruited in a retrospective analysis. Ishak, Metavir, and BA-specific staging systems in relation to outcomes were analyzed using logistic regression, COX proportional hazard regression, Kaplan-Meier analysis, etc. RESULTS: Kaplan-Meier analysis determined a significant difference in native liver survival according to the BA-specific stage (p = 0.002). The ROC curve analysis for predicting prognosis showed that the AUC of BA-specific staging combined with iBALF and severe bile duct proliferation (BDP) (0.811, 95% CI: 0.710-0.913, p < 0.0001) was higher than BA-specific staging alone (0.755, 95% CI: 0.639-0.872, p < 0.001). CONCLUSIONS: The BA-specific staging system reflects the condition of the liver fibrosis, and its combination with iBALF and severe BDP helps to better evaluate the prognosis of patients with BA.

Laparoscopic versus open Kasai procedure for biliary atresia: long-term results of a randomized clinical trial.

PURPOSE: The role of the laparoscopic approach for the Kasai procedure in the management of biliary atresia is still controversial. The aim of this study is to compare the long-term results of the laparoscopic Kasai procedure (LKP) to the open Kasai procedure (OKP). METHODS: A randomized clinical trial was carried out from October 2009 to March 2017. Patients diagnosed with biliary atresia type III were randomized into 2 groups: one group underwent LKP and the other group-OKP. All the surgical procedures were performed by the same surgeon with the same technical principles. The long-term outcomes were compared between the two groups. RESULTS: 61 patients underwent LKP and 61 patients-OKP, with a median age at the surgery of 79.7 days. The two groups had no significant differences regarding the patients' baseline characteristics. At follow-up up to 142 months, the jaundice-free rate at the 6th postoperative month for LKP and OKP was 52.5% and 60.7%, respectively (p = 0.23). The 10-year cumulative survival after LKP tended to be inferior to OKP, respectively 44.3% vs. 58.9% (p = 0.09). CONCLUSIONS: In this study, the long-term results of LKP tended to be inferior compared to OKP although the differences were not significant.

Peri-Kasai portoenterostomy sutures anchoring the jejunal loop to Glisson capsule: A novel modification to reduce the incidence of cholangitis.

BACKGROUND: Kasai portoenterostomy (KPE) is the standard surgical management for biliary atresia (BA). To improve the outcome these infants were operated on within the first two months of life. The success of the procedure is reflected by clearance of jaundice and either absence or occurrence of fewer attacks of cholangitis. The failure of the procedure indicates liver transplantation (LT). OBJECTIVE: to reduce the incidence of the recurrent attacks of cholangitis by peri-KPE sutures anchoring the jejunal loop to the Glisson capsule. METHODS: It is a retrospective study that included 45 infants diagnosed with BA and who were operated on at an age younger than 60 days. They were categorized into two groups, Group A (n = 23) included infants treated with the classic KPE, and Group B (n = 22) included infants treated in the same way plus peri KPE sutures anchoring the jejunal loop to the Glisson capsule. RESULTS: The mean operative time in Group A was 149.3 min versus 164.8 min in Group B (p-value 0.039). The mean level of bilirubin was 2.2 versus 2.1 in Group A and Group B respectively at two years follow up. The total attacks of cholangitis per patient were significantly lower in Group B than in Group A (cutoff value = 3), which was reflected by the significant reduction of the incidence of LT in Group B. CONCLUSION: peri KPE sutures anchoring the jejunal loop to the Glisson capsule significantly reduced the incidence of recurrent attacks of cholangitis and subsequently decreased the requirement of LT on the short-term follow-up.

Are the Post-transplant Outcomes of Kasai's Early Failure and Late Failure Comparable to the Primary Liver Transplantation?

It is uncertain whether prior Kasai procedures negatively impact the outcomes of liver transplantation (LT). The prior meta-analysis did not distinguish between Kasai early failure (K-EF) and late failure (K-LF). Numerous studies have been recently published; therefore, we perform a systematic review and meta-analysis. We searched PubMed and Embase databases to identify studies comparing the outcomes of biliary atresia (BA) patients undergoing primary LT versus patients with prior Kasai procedures. Subgroup analysis was done at the time of Kasai failure (early vs. late). Twenty-five studies comprising 6,408 patients receiving LT were included in the analysis. We found a statistically significant increase in one-year graft survival in K-LF versus primary liver transplant (pLT) (P = 0.0003). One-year patient survival was also increased in K-LF, although not statistically significant (P = 0.09). No difference in the one- and five-year graft and patient survival, reoperation rate, infection, and biliary complication was seen in pLT vs overall prior Kasai (K-EF and K-LF). These results suggest that prior kasai procedure does not negatively impact the outcome of LT. In addition, BA patients with prior Kasai undergoing LT later in life tend to perform better than primary liver transplants.

The Development of an Enhanced Recovery Protocol for Kasai Portoenterostomy.

Balancing post-operative adequate pain control, respiratory depression, and return of bowel function can be particularly challenging in infants receiving the Kasai procedure (hepatoportoenterostomy). We performed a retrospective chart review of all patients who underwent the Kasai procedure from a single surgeon at Children's Healthcare of Atlanta from 1 January 2018, to 1 September 2022. 12 patients received the Kasai procedure within the study period. Average weight was 4.47 kg and average age was 7.4 weeks. Most patients received multimodal pain management including dexmedetomidine and/or ketorolac along with intravenous opioids. A balance of colloid and crystalloids were used for all patients; 57% received blood products as well. All patients were extubated in the OR and transferred to the general surgical floor without complications. Return of bowel function occurred in all patients by POD2, and enteral feeds were started by POD3. One patient had a presumed opioid overdose while admitted requiring a rapid response and brief oxygen supplementation. Simultaneously optimizing pain control, respiratory safety, and bowel function is possible in infants receiving the Kasai procedure. Based on our experience and the current pediatric literature, we propose an enhanced recovery protocol to improve patient outcomes in this fragile population. Larger, prospective studies implementing an enhanced recovery protocol in the Kasai population are required for stronger evidence and recommendations.

Outcomes of Biliary Atresia in a Single Center in Jeddah, Saudi Arabia.

Background Biliary atresia (BA) is a rare but severe cause of obliterative cholangiopathy in neonates. Its incidence differs worldwide varying from 5/100,000 to 32/100,000 live births. The highest incidence is seen in Asia and the Pacific region. Diagnosing this disease is difficult in its early stages; thus, screening is necessary to avoid serious complications that can be minimized with early intervention during the first few months of life. Currently, although there are no medical treatments for BA, once the diagnosis is confirmed, the Kasai procedure may be a treatment option. The earlier the Kasai surgery is performed, the higher the success rate. Liver transplantation may be needed if the operation fails. This study aimed to determine the incidence of BA and the factors influencing the outcomes of the Kasai procedure at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Methodology This retrospective cohort study was conducted in the Pediatric Department at King Abdulaziz University Hospital, Jeddah from January 2019 to July 2019 and included consecutive patients with BA from 2010 to 2018. Results In total, 14 patients (57.1% female) were included in the study. The median age at the time of presentation was 90 (19-720) days, and the median age at the time of implementing the Kasai procedure was 90 (60-150) days. Eight patients underwent the Kasai procedure, and only one patient had a liver transplant. Conclusions Antenatal screening for BA tended to ensure early diagnosis and better outcomes. Delay in diagnosis and intervention is associated with increased morbidity and mortality.

Characteristics of the Gut Microbiome and IL-13/TGF-ß1 Mediated Fibrosis in Post-Kasai Cholangitis of Biliary Atresia.

Aims: Cholangitis in biliary atresia (BA), which accelerates liver fibrosis progression, is among the most common serious complications after Kasai surgery; however, its etiology remains elusive. Gut microbiome migration may contribute to post-Kasai cholangitis. Further, there is no appropriate model of BA post-Kasai cholangitis for use in investigation of its pathogenesis. Methods: We explored the characteristics of gut microbiome in patients with BA before and after Kasai procedure based on 16S rDNA sequencing. We isolated the dominant strain from patient stool samples and established an in vitro model by infecting patient-derived liver organoids. Bulk RNA-seq was performed, and we conducted qPCR, ELISA, and western blot to explore the mechanism of fibrosis. Results: Gut microbiome diversity was lower in patients after, relative to before, Kasai procedure, while the relative abundance of Klebsiella was higher. Patients who developed cholangitis within 1 month after discharge tended to have simpler gut microbiome composition, dominated by Klebsiella. Klebsiella pneumoniae (KPN) was isolated and used for modeling. RNA-seq showed that BA liver organoids expressed markers of hepatic progenitor cells (KRT19, KRT7, EPCAM, etc.) and that organoids were more stable and less heterogeneous among individuals than liver tissues. After infection with KPN, gene expression patterns in BA liver organoids were enriched in pathways related to infection, apoptosis, and fibrosis. Preliminary experiments indicated the presence of IL-13/TGF-ß1-mediated fibrosis in post-Kasai cholangitis. Conclusions: Our findings using a newly-developed model, demonstrate a key role for Klebsiella, and a potential mechanism underlying fibrosis in post-Kasai cholangitis, mediated by the IL-13/TGF-ß1 pathway.

Management of biliary atresia: To transplant or not to transplant.

Kasai procedure (KP) and liver transplantation (LT) represent the only therapeutic options for patients with biliary atresia (BA), the most common indication for LT in the pediatric population. However, KP represents by no means a radical option but rather a bridging one, as nearly all patients will finally require a liver graft. More and more experts in the field of transplant surgery propose that maybe it is time for a paradigm change in BA treatment and abandon KP as transplantation seems inevitable. Inadequacy of organs yet makes this option currently not feasible, so it seems useful to find ways to maximize the efficacy of KP. In previous decades, multiple studies tried to identify these factors which opt for better results, but in general, outcomes of KP have not improved to the level that was anticipated. This review provides the framework of conditions which favor native liver survival after KP and the ones which optimize a positive LT outcome. Strategies of transition of care at the right time are also presented, as transplantation plays a key role in the surgical treatment of BA. Future studies and further organization in the transplant field will allow for greater organ availability and better outcomes to be achieved for BA patients.

A Rare Dual Diagnosis of Duodenal and Biliary Atresia in a Premature Infant.

We present a case of a baby conceived via in vitro fertilization and born prematurely with duodenal atresia. It was later discovered that the patient also had biliary atresia. Both defects were repaired surgically via duodeno-duodenostomy and Kasai procedures, respectively. Our case presents the rare event of both duodenal and biliary atresia as well as management in this case. Although this dual diagnosis is relatively uncommon, such a possibility should be considered in certain cases. This case also adds to the literature opening up further investigation for a likely link between these two anomalies.

Sequential Treatment of Biliary Atresia With Kasai Hepatoportoenterostomy and Liver Transplantation: Benefits, Risks, and Outcome in 393 Children.

Introduction: Surgical treatment of biliary atresia (BA) is still based on sequential strategy with Kasai hepatoportoenterostomy (KP) followed by liver transplantation (LT), in case of complicated secondary biliary cirrhosis. Concerns have been expressed regarding the risks of LT related to previous KP, suggesting primary LT as an exclusive treatment of BA. Methods: Single-center retrospective analysis including 393 pediatric patients who underwent LT for BA from 1993 to 2018, categorized into two groups: with (KP) or without (NoKP) previous KP. Pre-LT clinical condition was estimated considering age at LT, time on waiting list, pediatric end-stage liver disease score (PELD), and presence of portal vein hypoplasia. Post-LT outcome was evaluated considering patient and graft survival rates, and need for early reoperation due to abdominal or graft-related complications (<45 days after LT). Results: Two-hundred ninety-six patients (75.3%) were categorized in the KP group, and 97 (24.7%) in the NoKP group. Median age at LT was 1.14 years in the KP group and 0.85 years in the NoKP group (p < 0.0001). PELD score was significantly less severe in KP patients (p < 0.05). One-year patient survival rates were 96.9 and 96.8% in the KP and NoKP groups, respectively (p = 0.43), and the corresponding graft survival was 92.5 and 94.8% (p = 0.97). The need for early reoperation was more frequent in the KP group (29.8%) vs. NoKP group (12.4%, p = 0.01). The rate of bowel perforation was non-significantly higher in the KP group (8.1%) vs. NoKP group (3.1%, p = 0.11). Conclusions: The sequential strategy including KP and LT allowed performing LT in patients with significant older age and better clinical conditions, when compared to those transplanted without previous KP. Patient and graft survivals were not impacted by previous KP. Although previous KP was associated with an increased rate of post-LT surgical complications, bowel perforation and bleeding did not occur significantly more frequently. Such results support the current strategy based on sequential treatment.

Growth Factors Assessed during Kasai Procedure in Liver and Serum Are Not Predictive for the Postoperative Liver Deterioration in Infants with Biliary Atresia.

BACKGROUND: Biliary atresia (BA) is a neonatal cholangiopathy characterized by progressive destruction of the biliary system resulting in liver cirrhosis. Residual bile drainage can temporarily be achieved through Kasai portoenterostomy (KPE) and some children show long-term survival with their native liver. However, most children eventually require liver transplantation (LTX). As several growth factors (GF) and chemokines have been shown to promote fibrogenesis in the liver, we assessed whether GF are predictive for the course of disease. MATERIAL AND METHODS: Liver and sera samples were collected from 49 infants with BA during KPE. Levels of 13 different GF were measured by multiplex immunoassay. Patient outcomes were stratified into favorable (bilirubin < 20 µmol/L at 2-year follow-up) and unfavorable (LTX). GF levels were compared between groups by a t-test, correlation coefficients were calculated, and principal component analyses performed. RESULTS: Twenty-two patients showed a favorable and 27 an unfavorable disease course. No relation of GF and outcome could be established. In both groups, high levels of SDF-1alpha/CXCL12 (1473.0 ± 497.5 pg/mL), FGF2 (301.2 ± 207.8 pg/mL), and VEGF-a (209.0 ± 146.4 pg/mL) levels were measured within the liver, followed (in descending order) by PDGF-bb, LIF, GM-CSF, BDNF, VEGF-d, beta-NGF, IL-7, SCF, PIGF-1, and EGF. Serum marker levels showed much higher mean variation compared to hepatic values and no correlation to the protein microenvironment in the liver. CONCLUSIONS: Our study demonstrates high amounts of GF in livers from infants with BA at KPE, but no correlation to the outcome or serum values could be established. Our data suggest that local or systemic GF levels are unsuitable for prediction of the disease course. Collectively, we conclude that in BA the degree of proliferative activity caused by GF is a dismissible factor for the further course of disease.

Biliary atresia liver histopathological determinants of early post-Kasai outcome.

BACKGROUND: A retrospective chart review of liver histologies in Kasai biliary atresia BA patients operated 1/2017- 7/2019 at our institution was conducted to identify histologic prognostic factors for biliary outcome. METHODS: Patients with wedge liver biopsies and portal plate biopsies (n = 85) were categorized into unfavorable and favorable outcome, based on a 3-month serum total bilirubin level of <34 µM or mortality. Hepatocellular histologies, presence of ductal plate malformation (DPM) and of large bile duct of ≥ 150 µm diameter size at the portal plate were evaluated. RESULTS: Total Bilirubin levels> 34 µM correlates with worse 1-year survival. Age at surgery, histologic fibrosis or inflammation does not predict outcome. Potential adverse predictors are severe hepatocellular swelling, severe cholestasis, presence of DPM (n = 24), and portal plate bile duct size < 150 µm (n = 28). In multivariate analyses adjusting for age at Kasai and postop cholangitis, bile duct size and severe hepatocellular swelling remain independent histologic prognosticators (OR 3.25, p = 0.039 and OR 3.26, p = 0.006 respectively), but not DPM. CONCLUSION: Advanced histologic findings of portal plate bile duct size of <150 µm and severe hepatocellular damage predict poor post-Kasai jaundice clearance and short-term survival outcome, irrespective of Kasai timing. LEVEL OF EVIDENCE: Level III.

[Dysregulated proportion of intrahepatic Treg cells and Th17 along with CD8+ T lymphocytes drives disease progression after kasai biliary atresia surgery].

Objective: To analyze the clinicopathological characteristics and intrahepatic immune cells infiltration condition after Kasai biliary atresia surgery. Methods: Data of 28 cases who underwent liver transplantation in the liver transplantation center of our hospital from June 2017 to March 2019 were enrolled. Of which, 20 cases were in the biliary atresia group (divided into two subgroups: 10 cases without Kasai surgery and 10 cases after Kasai surgery, and latter subsided cholestasis) and 8 cases in the control group. Clinical and pathological morphological characteristics of the groups were compared. Liver tissue sections were stained with immunohistochemistry and CD3, CD4, CD8, CD20, Foxp3, and interleukin-17A were quantitatively analyzed. Kruskal-Wallis test was used to measure the above indicators, and rank-sum test or Fisher's exact test was used to compare the count data. Results: The degree of clinical and pathological cholestasis in the biliary atresia group after Kasai surgery was significantly lower than that of the group without Kasai surgery, and the degree of liver fibrosis was also significantly reduced (P < 0.05), but there was no statistically significant difference in the degree of inflammation in the portal vein area between the two groups (P > 0.05). There was statistically significant difference in the types of immune cells infiltrated in the liver (P < 0.05). Compared with the group without Kasai surgery, the infiltration of CD3, CD8, IL-17A and Foxp3 positive cells in the portal vein area after Kasai surgery group (P < 0.05) was significantly reduced, but there was no statistically significant difference in the proportion of Foxp3/CD4 positive cells between the two groups (P > 0.05), which continued to be lower than that of the control group (P < 0.05). Compared with the non-Kasai surgery group, the proportion of Foxp3/IL-17A and Foxp3/CD8 positive cells in the portal vein area did not increase significantly after Kasai surgery group (P > 0.05), and remained lower than the control group. However, the proportion of Foxp3/IL-17A and Foxp3/CD8 positive cells was significantly reduced (P ​​< 0.05). Conclusion: Intrahepatic inflammatory cell infiltration and regulatory/effector T lymphocyte proportion dysregulation exist in patients with subsided cholestasis after Kasai biliary atresia surgery, which may be an important factor to promote the disease progression.