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.

Knowledge and practice of health workers towards maternal and child health in the Democratic Republic of the Congo: a cross-sectional study.

BACKGROUND: The burden of maternal and child mortality is high in the Democratic Republic of the Congo (DRC). While health workers (HWs) with adequate knowledge and practice of maternal and child health (MCH) are crucial to reduce this burden, the skill level of HWs in charge of MCH in the DRC is currently insufficient. This study aimed to assess the knowledge and practice of HWs towards MCH in Kasai and Maniema, two DRC provinces with very high maternal mortality ratios and under-5 mortality rates. METHODS: This cross-sectional study was conducted in 96 health facilities of Kasai and Maniema provinces in 2019. All HWs in charge of MCH were eligible for the study. Data were collected using a structured questionnaire containing 76 questions on knowledge and practice of MCH. Analyses were performed using the Wilcoxon-Mann-Whitney test, Kendall's correlation test, and a multivariate linear mixed regression model. RESULTS: Among participating HWs, 42.6% were A2 nurses (lowest qualification), 81.9% had no up-to-date training in MCH, and 48.4% had only 1-5 years of experience in MCH. In the two provinces combined, about half of HWs had poor knowledge (50.6%) and poor practice (53.3%) of MCH. Knowledge and practice scores were higher in Maniema than in Kasai (P < 0.001). Good knowledge and practice scores were significantly associated with high qualification (P = 0.001), continuing up-to-date training in MCH (P = 0.009), and 6 years of experience or more in MCH (P = 0.01). CONCLUSION: In Maniema and Kasai provinces, about half of HWs had poor knowledge and poor practice of MCH. The conversion of A1 nurses into midwives as well as the provision of up-to-date training in MCH, supervision, and mentorship could improve the skill level of HWs and could thus reduce the burden of MCH in the DRC.

This study assessed the knowledge and practice of health workers (HWs) towards maternal and child health (MCH) in Kasai and Maniema, two provinces of the Democratic Republic of the Congo (DRC) with very high maternal and child mortality rates. About half of surveyed HWs had poor knowledge and poor practice of MCH. Good knowledge and good practice were associated with high qualification, up-to-date training, and 6 years of experience or more in MCH. The conversion of A1 nurses into midwives as well as the provision of up-to-date training in MCH, supervision, and mentorship could improve the skill level of HWs and could thus reduce the burden of MCH in the DRC.

Cholestasis after Kasai operation predicts portal hypertension in native liver survivors of biliary atresia: a multicenter study.

PURPOSE: This study evaluated portal hypertension (PHT) and its predictors among native liver survivors (NLS) of biliary atresia (BA) after Kasai portoenterostomy (KPE). METHODS: This was a multicenter study using prospectively collected data. The subjects were patients who remained transplant-free for 5 years after KPE. Their status of PHT was evaluated and variables that predicted PHT were determined by regression analysis and receiver operating characteristic (ROC) curve. RESULTS: Six centers from East Asia participated in this study and 320 subjects with KPE between 1980 to 2018 were analyzed. The mean follow-up period was 10.6 ± 6.2 years. At the 5th year after KPE, PHT was found in 37.8% of the subjects (n = 121). Patients with KPE done before day 41 of life had the lowest percentage of PHT compared to operation at older age. At 12 months after KPE, PHT + ve subjects had a higher bilirubin level (27.1 ± 11.7 vs 12.3 ± 7.9 µmol/L, p = 0.000) and persistent jaundice conferred a higher risk for PHT (OR = 12.9 [9.2-15.4], p = 0.000). ROC analysis demonstrated that a bilirubin level above 38 µmol/L at 12 months after KPE predicted PHT development (sensitivity: 78%, specificity: 60%, AUROC: 0.75). CONCLUSIONS: In BA, early KPE protects against the development of PHT among NLSs. Patients with persistent cholestasis at one year after KPE are at a higher risk of this complication. They should receive a more vigilant follow-up. LEVEL OF EVIDENCE: Level III.

Inflammation patterns in early post-operative cholangitis predict long-term outcomes in biliary atresia: a potential role of non-suppurative cholangitis.

PURPOSE: Frequent post-operative cholangitis in biliary atresia (BA) affects the long-term native liver survival. This study assessed the characteristics of early cholangitis and their influence on the prognosis. METHODS: Forty-three patients with BA who underwent surgery between 2000 and 2020 were analyzed for routine inflammatory markers. Early cholangitis characteristics were compared between native liver survivor (NLS) and living donor liver transplant (LDLT) patients. RESULTS: Among the 43 patients, 30 (69.8%) experienced 130 episodes of cholangitis. In the area under the receiver operating characteristics curve (AUROC) analysis, the cutoff value of the total cholangitis episodes was 3, with an area under the AUROC curve of 0.695 (95% confidence interval 0.522-0.868). Before 3 years old, 113 episodes (86.9%) of cholangitis were observed. The white blood cell, C-reactive protein, and alanine aminotransferase values at cholangitis onset did not markedly differ between the LDLT and NLS groups. Conversely, the neutrophil-to-lymphocyte ratio in the NLS group was significantly lower than in the LDLT group (0.85 vs. 1.63, p < 0.001). CONCLUSIONS: Cholangitis in the NLS group was lymphocyte-dominant and atypical in its pathogenesis. Lymphocyte-dominant cholangitis is non-suppurative, and future research should clarify its pathogenesis to improve the treatment and prognosis of BA.

Delphi Method Analysis and Consensus of Prevalent Distinctive Practices for Biliary Atresia Management after Kasai Portoenterostomy.

Background: Extrahepatic biliary atresia (BA) is seen in infants, with an incidence of 1 in 15,000 live births. The presentation is progressive jaundice, dark-colored urine, and clay-colored stools. Kasai portoenterostomy (KPE) is the commonly performed surgical procedure in these patients. Postoperatively, phenobarbitone, ursodeoxycholic acid (UDCA), steroids, and other drugs are given to improve bile drainage and prevent inflammation and fibrosis. However, a definitive protocol regarding the need for different drugs, dosage, and duration varies across individual surgeons and centers. No universally accepted protocol exists for postoperative management after KPE. Aim: The aim of this study was to know the prevailing postoperative management of BA by subject experts and use the Delphi process to know if the experts want to change their practice based on the results from the survey. Material and Methods: A questionnaire was made after discussing with two experts in the field of BA. The questionnaire was mailed to 25 subject experts. The first survey data were analyzed and shared with all responders. In the second survey, change in the management based on the results from the first survey was assessed. Results: The Delphi questionnaire was answered by 17 experts. Postoperatively, prophylactic antibiotics are prescribed for 6-12 weeks by around 40% and >12 weeks by 30% of respondents. Phenobarbitone is prescribed for <3 months by nearly 50%. UDCA is prescribed for <3 months, ≤6 months, and 6 months-1 year by 47.1%, 23.5%, and 23.5% responders, respectively. Nearly 50% prescribe steroids (mostly prednisolone), and among them, two-thirds prescribe it for 6-12 weeks. Approximately 60% give antiviral drugs to children who are cytomegalovirus immunoglobulin M positive. In our survey, 50% of experts perform 5-10 KPE per year, and 25% each perform 10-15 and >15 KPE per year. The second survey noted that a significant percentage of responders want to change their practice according to consensus. Conclusion: From our Delphi survey, an overview of the postoperative management of BA could be made. However, multicentric studies are required for uniform protocol on the postoperative management of BA.

Predictive model containing gene signature and shear wave elastography to predict patient outcomes after Kasai surgery in biliary atresia.

AIMS: Infants with biliary atresia (BA) are treated with Kasai portoenterostomy (KPE) surgery, but many BA patients need subsequent salvage liver transplants. The aim of this study is to develop a comprehensive gene-clinical model based on two-dimensional shear wave elastography (2DSWE), liver gene expression, and other clinical parameters to predict response to KPE for BA patients. METHODS: Differentially expressed gene patterns between liver samples of BA (n = 102) and non-BA control (n = 14) were identified using RNA sequencing analysis. Biliary atresia patients were then randomly assigned to training and validation cohorts. Gene classifier based on the differentially expressed genes was built in the training cohort. Nomogram models with and without gene classifier were further constructed and validated for predicting native liver survival of BA patients. The utility of the nomograms was compared by C-index. RESULTS: Using the least absolute shrinkage and selection operator model, we generated a nine-gene prognostic classifier. The nomogram based on the nine-gene classifier, age, preoperative 2DSWE, and albumin had the better C-index compared to gene classifier alone in the training cohort (0.83 [0.76-0.90] vs. 0.69 [0.61-0.77], p = 0.003) and the validation cohort (0.74 [0.67-0.82] vs. 0.62 [0.55-0.70], p = 0.001). Using risk scores developed from the nomogram, the 12-month survival rates of BA patients with native liver were 35.7% (95% confidence interval [CI], 22.7-56.3) in the high-risk group and 80.8% (95% CI, 63.4-100.0) in the low-risk group in the validation cohort. CONCLUSIONS: The comprehensive genetic-clinical nomogram based on preoperative 2DSWE, liver gene expression, and other clinical parameters can accurately predict response to KPE.

Robotic-assisted Kasai portoenterostomy for biliary atresia.

BACKGROUND: Robotic-assisted Kasai portoenterostomy (RAKPE) has been utilized to treat biliary atresia (BA). However, RAKPE is not widely performed and its efficacy remains unknown. We summarized the experience of RAKPE for BA and determined its efficacy. MATERIALS AND METHODS: We retrospectively analyzed 25 consecutive infants with non-syndromic type III BA who received RAKPE in our center from January 2020 to July 2021. RAKPE is a three-arm setup and four-trocar operation. Bipolar coagulation was used to dissect the small blood vessels at the hepatic portal. The fibrous cone was shallowly transected with bending electric scissors, followed by gelatin sponge compression to staunch the hemorrhage. Finally, a wide anastomosis was accurately constructed. Demographics and outcomes were recorded. RESULTS: The mean operative time was 211.64 ± 18.93 min. No conversion to laparotomy or intraoperative complications occurred. The mean estimated blood loss was 7.64 ± 2.43 mL. Enteral feeding was resumed after 3.44 ± 1.23 days. All patients achieved bile excretion postoperatively, and dark green bile-stained stools were passed 1.50 days (range 1.00-3.00 days) after surgery. The average postoperative length of hospital stay was 10.32 ± 2.59 days. The jaundice clearance (JC) rate was 76.00% within 6 months after surgery and the incidence of cholangitis was 48.00% within 1 year following surgery. The survival with native liver (SNL) rate was 80.00% at 1 year and 66.67% at 2 years. CONCLUSION: RAKPE can be regarded as a treatment option for patients with BA due to the good outcomes reported. However, long-term studies comparing open or laparoscopic approaches are needed.

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.

Benefit of epidural analgesia for postoperative pain control after a Kasai Portoenterostomy: A ten-year retrospective cohort study.

INTRODUCTION: Biliary atresia is a rare obstructive cholangiopathy that presents in infants. The Kasai portoenterostomy procedure, which reestablishes biliary drainage into the intestine, is a surgical procedure that has been found to improve survival with the native liver. The options for postoperative analgesia include systemic opioids and epidural analgesia. The primary objective of this study was to compare the postoperative systemic opioids used in morphine equivalents (mg/kg) on postoperative days 0 through 3 between patients who underwent a Kasai portoenterostomy and received a thoracic epidural infusion to those without thoracic epidural analgesia. METHODS: We conducted a retrospective cohort study of 91 infants with biliary atresia undergoing a Kasai portoenterostomy between January 1, 2009, and September 1, 2019, at the Children's Hospital of Philadelphia. RESULTS: Sixty-three of the 91 patients (69%) had a continuous epidural catheter placed intraoperatively for postoperative analgesia. The total opioid requirement (morphine equivalents) for the first 72 h in the epidural group of (Mean (95% confidence interval): 0.52 mg/kg (0.38, 0.67 mg/kg) was lower than the non-epidural group (Mean (95% confidence interval): 1.15 mg/kg (0.8, 1.48 mg//kg) for a difference in mean opioid requirement (95% confidence interval) of 0.63 mg/kg (0.32, 0.94 mg/kg). Patients in the non-epidural group had higher rates of unplanned ICU admissions (36% non-epidural group vs. 3.3% epidural group, difference in proportion (95% confidence interval) 32.7% (13, 52%), p < .01). A higher percentage of patients in the non-epidural group had a postoperative oxygen requirement (32.1% vs. 11.3%, difference in proportion (95% confidence interval) 21% (2, 40%), p = .02). CONCLUSION: In our cohort study, continuous thoracic epidural analgesia in patients undergoing a Kasai portoenterostomy was associated with lower postoperative opioid use. We also observed that the epidural group had a lower ICU admission rate and a lower rate of postoperative supplemental oxygen requirement over the first three postoperative days.

Small Intestinal Adenocarcinoma Arising at the Anastomotic Site after Kasai Operation for Biliary Atresia: A Case Report and Literature Review.

Biliary atresia is an obliterative cholangiopathy of unknown etiology. Hepatic portoenterostomy, in which obliterated extrahepatic bile ducts are resected and bile flow is restored, known as Kasai operation, is performed within 3 months after birth. While this operation enhances long-term survival of patients, the occurrence of primary malignant hepatic tumors has been increasing. We report a case of small intestinal adenocarcinoma arising at the anastomotic site after Kasai operation. A 49-year-old man, who underwent Kasai operation for biliary atresia when he was 2 months old, experienced rapidly progressive jaundice and liver dysfunction. Deceased-donor liver transplantation was performed for liver failure. Macroscopically, there was a white-yellow tumor located at the anastomotic site of hepatic portoenterostomy of the resected liver. Pathological examination revealed a well-differentiated adenocarcinoma with some Paneth cells in the neoplastic lesion. Immunohistochemically, the tumor cells were negative for cytokeratin 7 (CK7) but positive for cytokeratin 20 (CK20) and a homeobox domain-containing transcription factor (CDX2). Mucin expression in tumor cells was negative for mucin 1 (MUC1) and mucin 6 (MUC6) and positive for mucin 2 (MUC2) and mucin 5AC (MUC5AC). The pathological diagnosis was small intestinal adenocarcinoma originating from the jejunum. The patient was discharged 48 days after the operation. The patient had not experienced recurrence at 10 months after the operation. This is the first report of small intestinal adenocarcinoma arising at the anastomotic site after Kasai operation for biliary atresia. Special care should be taken for the patients after Kasai operation with acute progressive jaundice and liver dysfunction because there is a possibility of malignancy in their native liver.

Laparoscopic versus open portoenterostomy for treatment of biliary atresia: a meta-analysis.

OBJECTIVE: Our goal was to compare laparoscopic portoenterostomy versus open portoenterostomy for the treatment of biliary atresia. MATERIALS AND METHODS: Using the databases EMBASE, PubMed, and Cochrane, we carried out a thorough literature search up to 2022. Studies comparing laparoscopic and open surgery for the treatment of biliary atresia were included. RESULTS: Twenty-three studies comparing laparoscopic portoenterostomy (LPE) (n = 689) and open portoenterostomy (OPE) (n = 818) were considered appropriate for meta-analysis. Age at surgery time was lower in the LPE group than OPE group (I2 = 84%), (WMD - 4.70, 95% CI - 9.14 to - 0.26; P = 0.04). Significantly decreased blood loss (I2 = 94%), (WMD - 17.85, 95% CI - 23.67 to - 12.02; P < 0.00001) and time to feed were found in the laparoscopic group (I2 = 97%), (WMD - 2.88, 95% CI - 4.71 to - 1.04; P = 0.002). Significantly decreased operative time was found in the open group (I2 = 85%), (WMD 32.52, 95% CI 15.65-49.39; P = 0.0002). Weight, transfusion rate, overall complication rate, cholangitis, time to drain removal, length of stay, jaundice clearance, and two-year transplant-free survival were not significantly different across the groups. CONCLUSIONS: Laparoscopic portoenterostomy provides advantages regarding operative bleeding and the time to begin feeding. No differences in remain characteristics. Based on the data presented to us by this meta-analysis, LPE is not superior to OPE in terms of overall results.

Prognostic factors and outcomes of Kasai portoenterostomy (KPE): nine-year experience from a lower-middle income country.

PURPOSE: Outcome data after Kasai portoenterostomy (KPE) reported worldwide show considerable regional and institutional variation. It is not known whether the same standards of outcomes reported in western world can be replicated in resource-poor countries. METHODS: We reviewed 79 patients of which 43 had completed a 2-year minimum follow-up. Two cohorts were based on age at KPE. The median age at surgery was 60 days. RESULTS: Clearance of jaundice (COJ) at 3 months was 20.93% and was not affected by age at surgery (p = 0.295). Four patients (9.3%) received liver transplant and 16 patients (37.21%) were recorded dead at a median age of 7 months. Native liver survival (NLS) was 53.49% and overall survival (OS) was 62.79%. Kaplan-Meier estimated 4- and 6-year NLS were 55.8% and 49.6%, respectively. There was a significant difference in the NLS between early and late surgery groups. CONCLUSION: While causes for low COJ need to be explored, these data reaffirm that early surgery has a significant favorable effect on survival. NLS was comparable with data from the developed world, whereas low OS is explained by limited access to transplant. Thus, where the survival depends on native liver longevity, emphasis should be on as early KPE as possible.

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.

Incidence and antiviral treatment of cytomegalovirus infection in infants with biliary atresia.

PURPOSE: Patients with biliary atresia (BA) and cytomegalovirus (CMV) infection may have poorer outcomes after Kasai portoenterostomy (KPE) than uninfected patients, suggesting a rationale for antiviral treatment (AVT). We aimed to describe the incidence of CMV infection and of AVT in BA patients, and to detect any differences between infected and uninfected patients to conclude if AVT is of use. METHODS: Data on BA patients who underwent KPE 2004-2020 were retrospectively collected, and the outcome was analyzed with regard to CMV status. RESULTS: Fifteen out of forty-six (33%) BA patients had signs of ongoing CMV infection. They did not differ significantly from the CMV-negative patients regarding rate of prematurity, birth weight, or biochemical markers but were slightly older at KPE. All patients received steroids postoperatively and all patients with ongoing CMV infection received AVT with very good effect on viremia and without major side effects. The AVT consisted of oral valganciclovir (10-40 (- 58) mg/kg/d) or intravenous ganciclovir (5.3-11 mg/kg/d). CONCLUSION: Ongoing CMV infection is common in this group of patients. The viremia can effectively be treated with AVT without any major side effects. Larger, randomized studies are needed to clarify the possible effect on clinical outcome.

A Randomized Control Trial to Evaluate the Effect of Local Instillation of Mitomycin-C at the Porta after Kasai Portoenterostomy in Patients of Biliary Atresia.

Background: Kasai portoenterostomy (KPE) is the initial treatment for biliary atresia (BA). Even after initial jaundice clearance, a significant number of children presented with the reappearance of symptoms due to ongoing fibrosis involving porta and intrahepatic ducts. Mitomycin-C (MMC) is an antifibrotic agent, and the study hypothesized that local application of MMC at porta can decrease fibrosis, which can improve jaundice clearance and lead to better native liver survival (NLS). Materials and Methods: This prospective randomized control trial included children with BA, who were allocated to groups A or B. The patients in both groups underwent standard KPE; in addition, a 5 French infant feeding tube (IFT) was placed near the porta through the Roux limb in Group B children. During the postoperative period, MMC was locally instilled over the porta in Group B children through IFT. Postoperative jaundice clearance and NLS were assessed and compared. Results: A total of 27 children were enrolled in the study, 16 in Group A and 11 in Group B. Both groups were comparable preoperatively. Although the NLS was not statistically significant in Group B, the survival was quite higher, that was 91%, 81%, and 73% at 6 months, 1 year, and 2 years, respectively, compared to 63%, 50%, and 38% in Group A. Conclusion: Children in Group B clinically showed an early jaundice clearance and a better trend of serial bilirubin levels as well as longer NLS than Group A, but it was not statistically significant. The procedure was technically easy, and no complication was encountered related to surgical technique or MMC instillation.

Serum matrix metalloproteinase-7 in biliary atresia: A Japanese multicenter study.

BACKGROUND: Biliary atresia (BA) is among the commonest indications for liver transplantation (LT) in children. We examined whether serum matrix metalloproteinase-7 (MMP-7) is useful for diagnosis of BA in Japanese infants, and whether serum MMP-7 concentrations before and after Kasai portoenterostomy (KP) predicted LT within a year. METHODS: Subjects under 6 months old at eight pediatric centers in Japan were enrolled retrospectively, including patients with cholestasis and normal controls (NC) without liver disease. Patients with cholestasis were divided into groups representing BA versus cholestasis from other causes (non-BA). Serum samples were collected from patients with BA at diagnosis and 1 and 4 weeks after KP, as well as from non-BA and NC. RESULTS: Serum MMP-7 concentrations were significantly higher in BA at diagnosis (median, 89.1 ng/ml) than in non-BA (11.0; p < 0.001) or NC (10.3; p < 0.001). Receiver operating characteristic (ROC) analysis of MMP-7 for BA versus non-BA yielded an area under the ROC curve of 0.99 (95% confidence interval, 0.96-1.00). An optimal cut-off value of 18.6 ng/ml for serum MMP-7 in diagnosing BA demonstrated sensitivity and specificity of 100% and 90%, respectively. Serum MMP-7 before and 1 week and 4 weeks after KP did not differ significantly between BA requiring only KP and BA requiring LT after KP. CONCLUSION: Serum MMP-7 is a useful marker for diagnosis of BA in Japanese infants, but it could not predict LT within a year.

Study protocol of Phase 2 open-label multicenter randomized controlled trial for granulocyte-colony stimulating factor (GCSF) in post-Kasai Type 3 biliary atresia.

Animal studies support RCT findings of improved liver function and short-term benefits using repurposed Granulocyte Colonic Stimulating Factor GCSF in adults with decompensated cirrhosis. We describe the protocol for phase 2 RCT of sequential Kasai-GCSF under an FDA-approved IND to test that GCSF improves early bile flow and post-Kasai biliary atresia BA clinical outcome. Immediate post-Kasai neonates, age 15-180 days, with biopsy-confirmed type 3 BA, without access to early liver transplantation, will be randomized 1:1 to standard of care SOC + GCSF at 10 ug/kg in 3 daily doses within 4 days of Kasai vs SOC + NO-GCSF (ClinicalTrials.gov NCT0437391). They will be recruited from children's hospitals in Vietnam, Pakistan and one US center. The primary objective is to demonstrate that GCSF decreases the proportion of subjects with a 3-month post-Kasai serum Total Bilirubin ≥ 34 umol/L by 20%, (for a = 0.05, b = 0.80, i.e., calculated sample size of 218 subjects). The secondary objectives are to demonstrate that the frequency of post-Kasai cholangitis at 6-month and 24-month transplant-free survival are improved. The benefits are that GCSF is an affordable BA adjunct therapy, especially in developing countries, to improve biliary complications, enhance quality of liver and survival while diminishing costly liver transplantation.Clinical trial registration: A phase 1 for GCSF dose and safety determination under ClinicalTrials.gov identifier NCT03395028 was completed in 2019. The current Phase 2 trial was registered under NCT04373941.

Portal plate bile duct diameter in biliary atresia is associated with long-term outcome.

PURPOSE: Kasai portoenterostomy (KPE) is the only treatment currently available for biliary atresia (BA). Age at KPE and surgical experience are prognostic factors for a successful KPE. Here, we aimed to assess whether the size of bile ductules at the porta hepatis during KPE correlates with KPE success and transplant-free survival (TFS). METHODS: A retrospective analysis of patients diagnosed with BA during 2000-2019. Porta hepatis biopsies were reviewed for diameters of five representative ducts, and a mean ductal diameter (MDD) was calculated. Laboratory values including pre- and postoperative bilirubin levels were analyzed. RESULTS: The cohort included 77 patients; for 33, ductal plate biopsy was available. KPE was successful in six of eight patients with MDD ≥ 50 µm, and in five of 25 with MDD < 50 µm, p = 0.008, OR = 12.0 (95% CI 1.83-78.3). Ten-year survival with native liver was higher in patients with MDD ≥ 50 µm than in patients with MDD < 50 µm, p < 0.001, HR 0.038 (95% CI 0.007-0.207). Direct bilirubin < 1 mg/dl 3 months post-KPE was associated with improved 2-year post-KPE TFS (27.7% vs. 13.9%, p < 0.0001). CONCLUSIONS: MDD ≥ 50 µm correlates with KPE success and a higher rate of TFS. Direct bilirubin < 1 mg/dl 3 months post-operation may serve as a marker of successful biliary excretion, and a predictor of 2-year TFS.

The need for early Kasai portoenterostomy: a Western Pediatric Surgery Research Consortium study.

PURPOSE: The purpose of this study was to investigate factors impacting transplant-free survival among infants with biliary atresia. METHODS: A multi-institutional, retrospective cohort study was performed at nine tertiary-level children's hospitals in the United States. Infants who underwent Kasai portoenterostomy (KP) from January 2009 to May 2017 were identified. Clinical characteristics included age at time of KP, steroid use, surgical approach, liver pathology, and surgeon experience. Likelihood of transplant-free survival (TFS) was evaluated using logistic regression, adjusting for patient and surgeon-level factors. Secondary outcomes at 1 year included readmission, cholangitis, reoperation, mortality, and biliary clearance. RESULTS: Overall, 223 infants underwent KP, and 91 (40.8%) survived with their native liver. Mean age at surgery was 63.9 days (± 24.7 days). At 1 year, 78.5% experienced readmission, 56.9% developed cholangitis, 3.8% had a surgical revision, and 5 died. Biliary clearance at 3 months was achieved in 76.6%. Controlling for patient and surgeon-level factors, each additional day of age toward operation was associated with a 2% decrease in likelihood of TFS (OR 0.98, 95% CI 0.97-0.99). CONCLUSION: Earlier surgical intervention by Kasai portoenterostomy at tertiary-level centers significantly increases likelihood for TFS. Policy-level interventions to facilitate early screening and surgical referral for infants with biliary atresia are warranted to improve outcomes.

Relationship between the expression levels of CD4+ T cells, IL-6, IL-8 and IL-33 in the liver of biliary atresia and postoperative cholangitis, operative age and early jaundice clearance.

OBJECTIVE: To investigate the expression levels of CD4+ T cells, IL-6, IL-8 and IL-33 in liver tissue of BA, and the relationship with postoperative cholangitis, operative age and early jaundice clearance. METHODS: 45 cases of jaundice treated in the hospital from June 2018 to May 2020 were analyzed retrospectively. The expression and distribution of these factors were detected by HE staining and immunohistochemistry, the total bilirubin level and the incidence of cholangitis were recorded, and the relationship between liver inflammation level and the postoperative incidence of cholangitis, age of operation and early jaundice clearance were compared. RESULTS: Immunohistochemistry showed that the expression of CD4+ T cells, IL-6, IL-8 and IL-33 in the BA group were higher than those in the CBD group. ROC curve analysis showed the AUC of CD4+ T cells, IL-6 and IL-8 were 0.869, 0.886 and 0.838, respectively. The expression level of CD4+ T cells was negatively correlated with the decline rate of TBIL 3 months after operation, and the expressions of IL-8 and IL-33 were negatively correlated with the decline rate of TBIL 1 week after operation. CONCLUSION: The high expression of CD4+ T cells, IL-6, IL-8 and IL-33 in the BA liver tissue may lead to cholangitis and can be used as a predictor of early jaundice clearance. The degree of liver inflammation infiltration had nothing to do with the age of operation and is not a risk factor for postoperative cholangitis.