Kasai Procedure in Patients Older Than 90 Days: Worth a Cut

Introduction Age at Kasai portoenterostomy (KPE) has been identified as a predictive factor for native-liver survival in patients with biliary atresia (BA). Outcomes of pediatric liver transplantation (LT) have improved over recent years. It has been proposed to consider primary LT as a treatment option for late-presenting BA infants instead of attempting KPE. We present our experience with patients older than 90 days undergoing KPE. Materials and Methods A retrospective chart review of patients with BA undergoing KPE at our institution between January 2010 and December 2020 was performed. Patients 90 days and older at the time of surgery were included. Patients' characteristics, perioperative data, and follow-up results were collected. Eleven patients matched the inclusion criteria. Mean age at KPE was 108 days (range: 90–133 days). Results Postoperative jaundice clearance (bilirubin < 2 mg/dL) at 2-year follow-up was achieved in three patients (27%). Eight patients (73%) received a liver transplant at a mean of 626 days (range: 57–2,109 days) after KPE. Four patients (36%) were transplanted within 12 months post-KPE. Two patients died 237 and 139 days after KPE due to disease-related complications. One patient is still alive with his native liver, currently 10 years old. Conclusion Even when performed at an advanced age, KPE can help prolong native-liver survival in BA patients and offers an important bridge to transplant. In our opinion, it continues to represent a viable primary treatment option for late-presenting infants with BA.

Identifying Biomarkers to Predict the Prognosis of Biliary Atresia by Weighted Gene Co-Expression Network Analysis

The prognosis of children with biliary atresia (BA) after Kasai operation remains difficult to predict, and liver fibrosis is closely related to the prognosis of children with BA. We aimed to find biomarkers for native liver survival (NLS) prediction by weighted gene co-expression network analysis (WGCNA). The biological processes and signal pathways that biomarkers involved in were further analyzed by bioinformatics. Quantitative Real-time PCR, Western blot and immunohistochemistry was performed to detect biomarkers expression. The relationship of biomarkers with clinicopathological characteristics of BA was also investigated. LECT2 was overexpressed or knockdown in LX-2 cells, and the expression of fibrogenic genes such as a-SMA and COL1A1 was quantified. We found that LECT2 mRNA expression was higher in BA liver tissues compared with normal liver tissues. Bioinformatics showed that LECT2 mainly played a fibrosis-promoting role in the development in BA by regulating bile acid metabolism and promoting inflammatory response. LECT2 immunohistochemistry scores of BA children were higher than control group (p = 0.001). Survival analysis revealed that LECT2 high expression is an unfavorable prognostic factor for native liver survival in BA patients. Additionally, the high LECT2 expression was an independent prognostic factor affecting native liver survival (HR 3.702, 95%CI:2.085–6.575, p = 0.001). LECT2 modulates TGF-β mediated a-SMA and COL1A1 expression in LX-2 cells. siRNA-LECT2 inhibits the expression of a-SMA and COL1A1 in LX-2 cells. Overexpression of LECT2 resulted in an increase in a-SMA and COL1A1 expression. Knockdown of LECT2 inhibits the proliferation and increase apoptosis in activated LX-2 cells. LECT2 may act as a new prognostic biomarker for native liver survival in BA patients.

Prognosis of Biliary Atresia Associated With Cytomegalovirus: A Meta-Analysis

Objective: The etiology of biliary atresia is unclear, but viral infection has been implicated. The aim of the current meta-analysis was to investigate relationships between cytomegalovirus (CMV) and the prognosis of biliary atresia.Methods: PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure database, and Wanfang Data electronic databases were searched for eligible studies. Each relevant text was thoroughly reviewed and examined, including related papers in their reference lists.Results: A total of nine studies including 784 patients were included in the analysis. Biliary atresia patients with CMV exhibited significantly lower jaundice clearance (odds ratio: 0.46, p &lt; 0.0001; I2 = 15%, p = 0.31). There were no significant differences in the rates of cholangitis or native liver survival. CMV-pp65-positive biliary atresia patients had a significantly lower rate of jaundice clearance (odds ratio: 5.87, p = 0.003; I2 = 0%, p = 0.71) and a significantly higher rate of cholangitis (odds ratio: 0.21, p = 0.01; I2 = 0%, p = 0.43) than CMV antibody-positive biliary atresia patients.Conclusion: Biliary atresia patients who were also infected with CMV had a poorer prognosis, particularly with respect to jaundice clearance. CMV status may influence the prognosis of biliary atresia. Clinicians should be able to routinely identify the subset of biliary atresia patients who are also CMV-positive, in order to improve native liver survival.

Stretching the Limit of Native Liver Survival in Biliary Atresia After Kasai Portoenterostomy – a 37-year Territory-wide Study

ObjectiveWe present a 37 years’ experience in the management of biliary atresia (BA) and discuss long-term complications after Kasai portoenterostomy (KPE).MethodsA retrospective territory-wide study from 1980 to 2017 on 231 patients with open KPE from three tertiary paediatric surgical centres was performed. The jaundice clearance (JC) rate, native liver survival (NLS) rate and complications were analyzed.ResultsThe mean follow up period was 15.4 +/- 6.2 years. Over 60% of patients remained JC within 2 years after KPE. Seventy patients (30.3%) received liver transplant (LT) at a median age of 6.2 years (range: 0.5 to 25 years). The NLS rates at 10, 20 and 30 years were 70.7%, 61.5% and 53.0% respectively with no significant change over the study period. The median bilirubin level among all native liver survivors (n=153) was 24 µmol/L (2 to 162 µmol/L). Portal hypertension (PHT) and recurrent cholangitis were found in 51.6% and 27.5% of them respectively.ConclusionWith a vigilant follow up program, more than 60% of BA patients could remain stable with the disease and achieve long term survival without LT. Although portal hypertension and recurrent cholangitis are common, they do not need to be the indications for LT if managed properly.

Postoperative intestinal obstruction in patients with biliary atresia impedes biliary excretion and results in subsequent liver transplantation

Purpose This study aimed to investigate the negative effects of intestinal obstruction for jaundice-free native liver survival after Kasai portoenterostomy (PE) for biliary atresia (BA). Methods We retrospectively reviewed the records of patients who underwent PE for BA between 2006 and 2019. We evaluated the postoperative morbidity of intestinal obstruction for up to 2 years after PE and the effects of intestinal obstruction on jaundice-free native liver survival. On the basis of their initial operation, patients were divided into open portoenterostomy (Open-PE) and laparoscopic portoenterostomy (Lap-PE) groups, and morbidity was compared. Results Of the 87 patients reviewed, 6 (6.9%) patients developed postoperative intestinal obstruction and underwent surgery to relieve the obstruction. The morbidity of early postoperative intestinal obstruction was 1.68 per 10,000 person days. The jaundice-free native liver survival rate among patients who once achieved jaundice-free status after PE was significantly lower in the patients with intestinal obstruction compared to in those without intestinal obstruction (0% vs. 73.8%; RR = 3.81, p = 0.007). No significant differences were seen in postoperative intestinal obstructions between the Open-PE and Lap-PE groups (p = 0.242). Conclusions Intestinal obstruction negatively impact jaundice-free native liver survival, even in patients who once achieved jaundice-free status after PE for BA.

Relevant factors for early liver transplantation after Kasai portoenterostomy

Background To explore the relevant factors for early liver transplantation (LT) after Kasai portoenterostomy (KP). Methods Retrospective analysis was performed for 200 children with biliary atresia, who underwent LT with hepatic failure after KP. According to the interval between KP and LT, they were divided into three groups: G1 (≤6-month), G2 (6-month~ 2-year) and G3 (> 2-year). Gender, age of Kasai portoenterostomy, jaundice-clearance, cholangitis after KP and liver function indexes before LT were compared among the three groups. Results The proportion of patients with age of KP (≤90-day) in G1 was lower than that in G3 (P = 0.003). Jaundice-clearance occurred in 6 (7.6%), 26(28.6%) and 26 (86.7%) patients after KP in G1, G2 and G3 respectively (P < 0.001). There were statistical differences in the incidence of early cholangitis, late cholangitis and repeated cholangitis among the three groups (P = 0.035, < 0.001 and 0.022). The native liver survival (NLS) rate of children at operation age > 90-day was lower than that of children at operation age ≤ 90-day (P = 0.002). The NLS rate of the children with jaundice-clearance after KP was significantly better than that of the children without jaundice-clearance (P < 0.001). The NLS rate of the children with early cholangitis after operation was lower than that in children without early cholangitis (P = 0.026). The NLS rate of patients of G2 and G3 with cholangitis after KP was lower than that in children without cholangitis (P = 0.017). Multiple logistic regression analysis showed uncleared jaundice after KP was a risk factor for the NLS time in patients. Conclusion The age of KP (> 90-day), jaundice-unclear and early cholangitis could reduce the NLS time after KP, which were related to early liver transplantation. Jaundice-unclear was a risk factor for early liver transplantation.