Postoperative Infection in Biliary Atresia Patients Reduces Early Bilirubin Clearance and Native Liver Survival: A Single - Center Retrospective Cohort Study

Postoperative Infection in Biliary Atresia Patients Reduces Early Bilirubin Clearance and Native Liver Survival: A Single - Center Retrospective Cohort Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Postoperative Infection in Biliary Atresia Patients Reduces Early Bilirubin Clearance and Native Liver Survival: A Single - Center Retrospective Cohort Study Xuan-Yu MENG, Shu-Heng LIANG, Li HUANG, Xiang YUN, Qing TANG, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7625443/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 15 You are reading this latest preprint version Abstract Background Besides to cholangitis, there are few reports on the influence of other infections post-Kasai procedure (KP) in biliary atresia (BA). The study is to investigate the prognosis associated with post-Kasai procedure (KP) infection. Methods This retrospective study included children with BA who underwent KP. Postoperative infection was the primary exposure variable of interest in this cohort. The primary outcome measure was post-operative native liver survival, while the secondary outcome measure was mortality attributed to infection. Results 1. A total of 404 cases included in the study. There were no significant differences in gender, age at operation, or gestational age between the two groups (P > 0.05). The native liver survival was 2.60 ± 2.95 years in the non-infected group, whereas it was reduced to 1.57 ± 1.70 years in the infected group (P < 0.01). Early-onset infection primarily impacts bilirubin clearance, resulting in delayed clearance of bilirubin (P < 0.01). Conclusion Postoperative infection in biliary atresia delays bilirubin clearance and reduces native liver survival. Biliary atresia Infect Cholangitis Liver function Infants Figures Figure 1 Figure 2 1. Introduction Biliary atresia (BA) is a disease of unknown etiology characterized by progressive inflammation and fibrotic obstruction of both intrahepatic and extrahepatic bile ducts. The prevalence of BA varies geographically worldwide, with East Asian countries exhibiting the highest incidence rates. Specifically, Japan has an incidence rate of 1.1–1.2/10000 and Taiwan region of China has a rate of 1.51–1.54/10000, while the United States has a lower range of 0.44–0.96/10000 and European countries have similar rates ranging from 0.5–0.58/10000 [ 1 – 7 ] . The primary clinical manifestations of BA include delayed resolution of jaundice after birth (in full-term infants > 2 weeks and preterm infants > 3 weeks), or recurrent episodes of jaundice with progressive worsening [ 8 ] . This may be accompanied by lightening of stool color until it becomes clay-colored, as well as liver and spleen enlargement, malnutrition, and delays in growth and development. Infection is a frequent complication following surgery, with cholangitis, bacterial pneumonia, septicemia, fungal infection being the most encountered types. Among these infections, cholangitis has the highest incidence rate, ranging from 40% to 93% [ 9 – 11 ] . It is generally believed that cholangitis shortens native liver survival in children and increases the risk of liver transplantation [ 12 , 13 ] . Studies indicate that children who experience early cholangitis have a significantly lower two-year native liver survival rate compared to those without such an occurrence [ 14 , 15 ] . However, in addition to postoperative cholangitis following BA surgery, there is a risk of other localized and systemic infections such as pneumonia and sepsis [ 11 , 16 ] . Currently, there is a paucity of relevant research literature examining the impact of postoperative infections other than cholangitis on both native liver survival and mortality. This study aims to investigate the risk factors associated with post-KP infection in children with BA and assess the impact of infection on native liver survival. 2. Methods 2.1 Participants The study was approved by the Ethics Committee of the First Affiliated Hospital of Guangxi Medical University (approval number 2023-K018-01) and conducted in accordance with the ethical standards laid down in the World Medical Association’s Declaration of Helsinki. The same committee waived the requirement for the acquisition of informed consent from parents or guardian owing to the retrospective nature of the study. Data were accessed for research from January 2012 to August 2022 at the First Affiliated Hospital of Guangxi Medical University. The retrospective single-center cohort study conducted included 404 children’s patients with BA who underwent Kasai procedure (KP). The inclusion criteria for BA require confirmation through surgical exploration, which can be classified into three types according to the Kasai classification system. Type I includes dendritic and cloudy common bile duct atresia, while type II involves hepatic duct atresia. Finally, type III refers to hilar atresia or complete extrahepatic bile duct obstruction [ 17 , 18 ] . The exclusion criteria encompass the coexistence of other systemic malformations, congenital genetic metabolic disorders, congenital immunodeficiency syndromes or inflammatory conditions in conjunction with BA. Children with BA who developed infection before surgery. 2.2 Definition of pertinent clinical indicators and diagnostic criteria (1) Infection: Infection refers to cholangitis, sepsis and respiratory infections. Early infection is defined as an infection occurring within 1 month after KP. "Late-onset infection" refers to an infection that occurs more than 1 month, and within 12 months for infections other than cholangitis, following the performance of KP. In the case of cholangitis, it is defined as an infection occurring in any time after KP. Frequent infections are those that occur three or more times within six months, while sporadic infections occur less than three times within six months [ 19 ] . (2) Cholangitis: Symptoms of a cholangitis attack include unexplained fever, worsening or receding yellowing of the skin and sclera, lighter stool color or reappearance of clay-colored stools, increased levels of serum bilirubin (total and direct), as well as significant increases in leukocytes, neutrophils, C-reactive protein and procalcitonin according to blood tests [ 19 , 20 ] . (3) Native liver survival: The starting point was the time after KP, and the end point was the period of liver decompensation or before liver transplantation or death due to liver failure. 2.3 Cohorts were stratified for analysis according to the presence or absence of infection as an exposure variable. The clinical data collected in this study encompassed demographic information such as gender and age at the time of operation, details regarding occurrence of postoperative infection, glucocorticoid usage, results from blood routine examination, liver function tests including total bilirubin (TBIL), direct bilirubin (DBIL), γ-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acids (TBA), and albumin (ALB) levels. The subjects were categorized into two groups based on the presence or absence of infection: non-infected group and infected group. Subsequently, subgroup analysis was conducted according to the type of infection, which included bacterial infection group, fungal infection group, and mixed infection group. According to the site of infection, the cohort was categorized into groups based on biliary tract infection, pulmonary infection, and systemic infection. The classification was also done according to the timing of infection: early-onset infection group, late-onset infection group, and recurrent infection group. The risk factors for postoperative infections in patients with BA and the incidence of infections at different sites were analyzed. Additionally, correlation analyses were performed to investigate the effects of age at operation, surgical approach, antibiotic and glucocorticoid duration, jaundice clearance rate, liver fibrosis, and native liver survival. 2.4 Follow-up and prognostic assessment Biochemical indicators such as liver function was followed up regularly 4 weeks, 8 weeks, 12 weeks, 6 months, and 12 months after KP. and the follow-up end points were liver transplantation (decompensation of liver failure), or death due to the liver failure. Survival analysis: Short-term survival: the native liver survival time was 5 years. 2.5 Statistical analysis SPSS 27.0 software was utilized for conducting statistical analysis on the data. The mean ± standard deviation ( \(\:\stackrel{-}{X}\) ±SD) was employed for measuring data that exhibited a normal distribution, while the median [P50 (P25, P75)] was used for measuring data that did not conform to a normal distribution. A two-independent sample t-test was conducted to compare between groups. The binary categorical variable was presented as percentages, and inter-group comparisons were conducted using either the chi-square test or Fisher's exact test. The Kaplan-Meier method was used to estimate the native liver survival. The log-rank test was employed to analyze differences in survival rates among different groups, while binary logistic regression was utilized to identify the independent risk factors for infections. A P value of less than 0.05 indicated a statistically significant difference. 3. Results 3.1 Demographic data of the cohort From January 2012 to August 2022, a total of 404 children with BA who underwent KP met the inclusion criteria. In the infection group, there were 240 BA patients, comprising of 118 (49.2%) male and 122 (50.8%) female. The age range for KP was between 39 to 248 days, with a median age of [75.5(63.0, 92.8)] days. The height ranged from 41cm to 75cm, with an average of 57.58 ± 4.03 cm, while the weight ranged from 2.2 kg to 9 kg, with an average of 5.09 ± 0.87 kg. BA type I accounted for only12 cases (5%), type II accounted for nine cases (3.8%), and type III accounted for most 219 cases in total (91.2%). In the non-infected group, there were 164 BA patients, comprising of 92 (56.1%) males and 72 (43.9%) females. The age at KP ranged from 40 to 210 days, with a median age of [75.0(62.0, 93.0)] days. The height ranged from 45 cm to 70 cm, with an average of 57.24 ± 3.90 cm, while the weight ranged from 2.1 kg to 8.5 kg, averaging at 4.88 ± 0.94 kg. BA type I was observed in 8 cases (4.9%) while type II and III were seen in 11 (6.7%) and one145(88.4%) cases respectively. There were no significant differences in gender, age of operation, height and type of BA between the two groups, all P > 0.05. Interestingly, the infected group exhibited a significantly higher weight compared to the non-infected group, with a statistically significant difference between the two groups, P < 0.05 (Table 1 ). Table 1 Comparison of demographic characteristics data Groups N Gender Age of operation (Day) Weight (kg) Height (cm) Liver fibrosis score Type I Type II Type II Male (%) Male (%) Non-infected group 161 89(55.28) 72 (44.72) 77.0(63.0,91.8) 4.88 ± 0.94 57.24 ± 3.90 2.74 ± 1.15 8 11 145 Infected group 240 118 (49.17) 122 (50.83) 75.0(62.0,93.0) 5.09 ± 0.87 57.58 ± 4.03 2.87 ± 1.20 12 9 219 χ2/t/Z 4.235 -0.175 -2.253 -0.818 -1.084 1.181 P 0.120 0.861 0.025 0.414 0.279 0.404 3.2 Etiological composition of infection and outcome A total of 240 cases were included in the infection group, of which 88 cases were detected positive pathogenic microorganisms, the positive rate of pathogen detection was 36.67%. Among the 88 cases, 58 (65.9%) were positive in blood culture, 32 (36.4%) in sputum culture, 5 in urine culture, 3 in ascites culture and 1 in bile culture. There were 27 fatalities attributed to infection, resulting in an infection-related mortality rate of 11.25% (27/240). Among them, 6 cases of cholangitis, and 21 cases of mixed infections.There were 5 cases of fungal infection among the mixed infections.Positive blood cultures were identified in 10 patients, including Klebsiella pneumoniae + Enterococcus faecalis (1case), Acinetobacter baumannii (2 cases), Enterobacter cloacae (1 case), Escherichia coli (3 cases), and Enterococcus faecalis (3 cases). Additionally, positive sputum cultures were found in 3 patients: Acinetobacter baumannii (1 case), Acinetobacter baumannii + Candida albicans (1 case) and Stenotrophomonas maltophilia (1case). Sepsis was present in 16 fatal cases (Table 2 ). Table 2 Common infectious bacteria and drug susceptibility results Pathogens of infection Number of cases Source of culture specimen Drug-sensitivity Klebsiella pneumoniae 17 Sputum, blood, urine, ascites Ciprofloxacin, Levofloxacin, Amikacin, gentamicin Escherichia coli 16 Blood and sputum Meropenem, imipenem, Amikacin Enterococcus faecium 12 Blood Vancomycin, Linezolid Baumanii 10 Blood and sputum Tigecycline Enterobacter cloacae 9 Blood Meropenem, imipenem, ciprofloxacin Candida albicans 7 Sputum, blood, urine, ascites Voriconazole, Diflucan Enterococcus faecalis 5 Blood Vancomycin, Linezolid, Levofloxacin Stenotrophomonas maltophilia 3 Blood, sputum, bile Levofloxacin, cotrimoxazole, ceftazidime Klebsiella oxytoca 2 Blood Cefoperazone sulbactam, ceftriaxone, meropenem, imipenem Serratia marcescens 2 Blood, sputum Cefoperazone sulbactam, Ceftriaxone, piperacillin tazobactam, meropenem, imipenem Pseudomonas aeruginosa 2 Blood, sputum Meropenem, imipenem, piperacillin tazobactam, cefoperazone sulbactam Moraxella osloensis 1 Blood Erythromycin Candida parapsilosis 1 Blood Drug sensitivity test was not performed Candida tropicalis 1 Sputum Drug sensitivity test was not performed 3.3 The impact of infection on prognosis 3.3.1 Effects of infection on native liver survival Among the 404 cases of follow-up, the native liver survival ranged from 0.2 to 14.2 years, with an average duration of 1.99 years. The mean native liver survival was 1.57 ± 1.70 years in the infection group, while the mean native liver survival was 2.60 ± 2.95 years in the non-infection group. Notably, there was a statistically significant difference between the native liver survival rates of infected and non-infected groups ( P < 0.05) (Fig. 1 ). The 2-year native liver survival rate was 41.46% (68/164) in the non-infected group and 25.42% (61/240) in the infected group, ( P < 0.05). Notably, the native liver survival was significantly lower in the infected group compared to the non-infected group ( P < 0.01) (Fig. 1 ). Subgroup analysis was performed among the 27 infection deaths showed that the native liver survival in the fungal infection group was significantly lower than the non-fungal infection group ( P = 0.013). 3.3.2 Effects of infection on liver function The levels of ALB in the infected group were significantly lower post-operation compared to those in the non-infected group during the 4 weeks, 8 weeks, 12 weeks, 6 months and 12 months followed up ( P = 0.026). The levels of TBIL and DBIL in the infected group were significantly higher post-operation compared to those in the non-infected group (all P 0.05), Fig. 2 . 4. Discussion Infectious complications are common following KP for BA. Typically, these include cholangitis, pneumonia, and sepsis. Pathogens include bacteria, cytomegalovirus, Epstein Barr virus, and fungal infections. The highest incidence among them is cholangitis, accounting for 40%-93% [ 9 ] . In this study, the overall infection rate was found to be 59.4%, with cholangitis accounting for a significant proportion at 90.8%. These findings align closely with previous studies conducted in the field [ 21 ] . In this study, 88 (36.7%) of infection patients were identified as pathogenic bacterial infections. The most prevalent pathogens identified were Escherichia coli and Enterococcus faecium, followed by Klebsiella pneumoniae and Enterobacter cloformis. These findings are consistent with previous research conducted the previous study [ 22 – 24 ] . In this study, most of the postoperative cases were treated with glucocorticoids, and the incidence of fungal infection was 10.4%. Results showed that glucocorticoid use more than 4 weeks was a risk factor for infections, especially fungal infections. The main pathogen of fungal infection is Candida, which is sensitive to drugs such as voriconazole and fluconazole. These findings are consistent with previous reports [ 25 ] . The findings of this study indicate that the fatality rate following infection is as high as 11.15%, with sepsis being the primary cause of mortality. The mortality rate following sepsis was found to be 59.26%, indicating a higher fatality rate associated with this condition. Therefore, early intervention and aggressive antimicrobial therapy can reduce the risk of death. However, the positive rate of traditional etiological detection methods, including blood culture, was very low. In this study, the positive rate of etiological detection was only 36.67%. With the development of science and technology, metagenomic next generation sequencing (mNGS) can be utilized in post-operative children with BA to enhance the positive detection rate of infectious pathogens [ 26 , 27 ] . Early detection and standardized treatment should be implemented to prolong the native liver survival. The impact of infection on liver function primarily manifests as a reduction in bilirubin clearance. Our study found that the jaundice clearance rate was 44.8% among non-infected patients, compared to 31.3% among infected patients. Cholangitis and frequent cholangitis exert the most significant impact on jaundice clearance, which is in line with the findings of the previous study [ 28 ] . The early clearance of bilirubin can ameliorate hepatocyte damage caused by cholestasis and retard the progression of cirrhosis [ 29 ] . The findings of this study demonstrate that cholangitis and recurrent cholangitis predominantly impact TBA and GGT levels, while albumin is affected in the context of any infection. Given that albumin serves as a marker for liver synthesis, it can be inferred that any infection will have an impact on hepatic synthesis. A study showed that achieving a postoperative bile acid level of less than 40 µmol/L could lead to a favorable prognosis [ 30 ] . Therefore, early identification of postoperative infection risk and prompt and appropriate anti-infective therapy can enhance the prognosis of BA. The presence of infection has a significant impact on the postoperative native liver survival of BA, as evidenced by a 2-year native liver survival rate of 40.4% for non-infected patients and only 25.4% for infected patients. The native liver survival in patients with fungal infection and frequent cholangitis was significantly shortened. These findings are in line with the notion that infection can impede jaundice clearance and hypoalbuminemia may result from reduced liver synthesis. As cholestasis cannot be promptly resolved, severe liver cell damage ensues, thereby compromising native liver survival. This study found that patients with a larger body weight or body mass index (BMI) are more likely to develop postoperative infections, but the number of infections is not high. Body weight is the most important and sensitive indicator reflecting the physical growth of children, and it is a comprehensive reflection of both short-term and long-term nutritional status. The body mass index (BMI) = body weight (kg) / height (m)². It can compare weight differences under the same height condition, effectively eliminating the influence of physical development differences caused by factors such as gender, development level, genetics, and ethnic differences before puberty. It is a sensitive indicator for judging emaciation in children and reflects the recent nutritional status [ 31 , 32 ] . Some studies have shown that the degree of preoperative malnutrition is positively correlated with the occurrence of cholangitis after biliary atresia surgery [ 33 ] . Since body weight is only one of the indicators for evaluating nutritional status, it cannot fully illustrate the true nutritional status of children before surgery. The small intestine is the largest digestive and absorptive organ in the human body, and its length is related to the individual's own body length [ 34 ] . Children with a larger body weight generally have a slightly longer height, so the length of their small intestine is longer than that of those with a smaller body weight. The length of the intestinal loop after Kasai surgery may be longer in children with a larger body weight compared to those with a smaller body weight, and the length and area of the small intestine for absorbing nutrients are larger. Due to the inconsistent growth and development rates of the small intestine and the mesentery, the excessively long jejunal biliary limb in children with good nutritional status is more likely to develop complications such as intestinal volvulus, intestinal obstruction, and cholestasis, increasing the occurrence of cholangitis. Secondly, in children with a longer intestinal loop, the risks of upward infection of intestinal bacteria and reflux of intestinal contents increase, both of which increase the incidence of cholangitis. However, the probability of frequent infections in children with a larger body weight is not high, which may be related to the nutritional status of the children [ 35 ] . In this study, the relatively large body weight of the children at the time of surgery may also be related to the relatively large age at the time of surgery. China is a developing country, and there is an imbalance in the development of economic and health levels. Guangxi is a relatively underdeveloped region in the western part of China. Children seek medical treatment relatively late, so the age at the time of surgery is relatively large. In conclusion infection significantly reduces the jaundice clearance rate, albumin levels and native liver survival in BA after KP. Declarations Conflict of Interest Statement: All the authors declare that there is no conflict of interest. Acknowledgements Not applicable. Authors' Contributions: XY MENG contributed to data collection, statistically analyzed, and drafting of the paper. L HUANG and X YUN contributed the sample collection and revision of the paper. Q TANG and XQ CHEN contributed the conception and design of study and revised the final paper. All authors reviewed the manuscript. Approval Committee or the Internal Review Board (IRB) ： The study was approved by the Ethics Committee of the First Affiliated Hospital of Guangxi Medical University (approval number 2023-K018-01) and conducted in accordance with the ethical standards laid down in the World Medical Association’s Declaration of Helsinki. The same committee waived the requirement for the acquisition of informed consent from parents or guardian owing to the retrospective nature of the study. Clinical trial number: Not applicable. Funding ： This study was supported by the Excellent Medical Talents Training Program of the First Affiliated Hospital of Guangxi Medical University, Guangxi Natural Science Foundation (no. 2024GXNSFAA010055), Guangxi Clinical Medical Research Center for Pediatric Diseases (Guike AD22035121), Middle/Young aged Teachers' Research Ability Improvement Project of Guangxi Higher Education (2024KY0093) , Clinical Research "Climbing" Program of the First Affiliated Hospital of Guangxi Medical University (YYZS2023011), Difficult and Critical illness Center, Pediatric Clinical Medical Research Center of Guangxi (Gui Ke AD22035219), and the Key Laboratory of Children's Disease Research in Guangxi’s Colleges and Universities, Education Department of Guangxi Zhuang Autonomous Region. Consent to Publish declaration: All authors approved the final submitted manuscript. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7625443","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":534679363,"identity":"370c4de8-f963-47c4-926f-3e26417c0334","order_by":0,"name":"Xuan-Yu MENG","email":"","orcid":"","institution":"Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region","correspondingAuthor":false,"prefix":"","firstName":"Xuan-Yu","middleName":"","lastName":"MENG","suffix":""},{"id":534679364,"identity":"10812b31-1eff-46a4-bae1-f9034272e345","order_by":1,"name":"Shu-Heng LIANG","email":"","orcid":"","institution":"Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region","correspondingAuthor":false,"prefix":"","firstName":"Shu-Heng","middleName":"","lastName":"LIANG","suffix":""},{"id":534679365,"identity":"b51be273-1fff-43a6-9d70-2b6e3218b549","order_by":2,"name":"Li HUANG","email":"","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Li","middleName":"","lastName":"HUANG","suffix":""},{"id":534679366,"identity":"38425df9-eb3f-4d6d-ae4d-738cc01b1303","order_by":3,"name":"Xiang YUN","email":"","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xiang","middleName":"","lastName":"YUN","suffix":""},{"id":534679367,"identity":"d98b00fc-8b94-4db0-ab2a-53136c7df782","order_by":4,"name":"Qing TANG","email":"","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical 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04:46:08","extension":"xml","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":87433,"visible":true,"origin":"","legend":"","description":"","filename":"76925a4987ef4c9fbc47e80652decaf01structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7625443/v1/18625a47bdb245d1d9c9d0ea.xml"},{"id":94625804,"identity":"3cbc3c0b-403d-49c1-b59d-a021ee36e376","added_by":"auto","created_at":"2025-10-29 04:46:08","extension":"html","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":97181,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7625443/v1/7c1736acc2939fe09b8c4658.html"},{"id":94625788,"identity":"2936af33-1af9-43cb-83be-3fee86bb245b","added_by":"auto","created_at":"2025-10-29 04:46:07","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":555536,"visible":true,"origin":"","legend":"\u003cp\u003eA, Native liver survival analysis in the infected group and non-infected group\u003c/p\u003e\n\u003cp\u003eB, Native liver survival analysis in subgroup among the early-onset infection group, late-onset infection group and non-infection group.\u003c/p\u003e\n\u003cp\u003eC, Native liver survival analysis in subgroup among the simple cholangitis group, simple pneumonia/bronchitis group, mixed infection group and non-infection group.\u003c/p\u003e\n\u003cp\u003eD, Native liver survival analysis in subgroup among the non-fungal infection group, fungal infection group and non-infection group.\u003c/p\u003e\n\u003cp\u003eE, Native liver survival analysis in subgroup among the frequent cholangitis group, non-frequent cholangitis group and non-infection group.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7625443/v1/653b17d43ef3694b01bc8f81.jpg"},{"id":94625795,"identity":"c74f8445-cf41-420b-aae9-8245635a976d","added_by":"auto","created_at":"2025-10-29 04:46:08","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":3470667,"visible":true,"origin":"","legend":"\u003cp\u003eThe indices of liver function after KP were compared between the infection group and the non-infection group.\u003c/p\u003e\n\u003cp\u003eThe levels of albumin (ALB) in the infected group were significantly lower at 4 weeks*, 8 weeks*, 12 weeks*, and 6 months* post-operation compared to those in the non-infected group (P \u0026lt; 0.05). The GGT levels at 12 weeks* and 6 months* post-KP in the infected group were elevated compared to the non-infected group (P \u0026lt; 0.05). The TBA in the infected group was elevated compared to the non-infected group at 6 months* post-surgery (P \u0026lt; 0.05). There was no statistically significant disparity in other liver function indicator between the infected and non-infected group at the one-year post operation (P \u0026gt; 0.05).\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7625443/v1/e7fd4dd48e7fd0001ee1c9b4.jpg"},{"id":94641108,"identity":"a4ada3ce-d580-4099-ac90-03d98df6921a","added_by":"auto","created_at":"2025-10-29 07:51:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4822455,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7625443/v1/bf53257c-50a6-43f4-963e-b6b477628e27.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Postoperative Infection in Biliary Atresia Patients Reduces Early Bilirubin Clearance and Native Liver Survival: A Single - Center Retrospective Cohort Study","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eBiliary atresia (BA) is a disease of unknown etiology characterized by progressive inflammation and fibrotic obstruction of both intrahepatic and extrahepatic bile ducts. The prevalence of BA varies geographically worldwide, with East Asian countries exhibiting the highest incidence rates. Specifically, Japan has an incidence rate of 1.1\u0026ndash;1.2/10000 and Taiwan region of China has a rate of 1.51\u0026ndash;1.54/10000, while the United States has a lower range of 0.44\u0026ndash;0.96/10000 and European countries have similar rates ranging from 0.5\u0026ndash;0.58/10000 \u003csup\u003e[\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5 CR6\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. The primary clinical manifestations of BA include delayed resolution of jaundice after birth (in full-term infants\u0026thinsp;\u0026gt;\u0026thinsp;2 weeks and preterm infants\u0026thinsp;\u0026gt;\u0026thinsp;3 weeks), or recurrent episodes of jaundice with progressive worsening \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. This may be accompanied by lightening of stool color until it becomes clay-colored, as well as liver and spleen enlargement, malnutrition, and delays in growth and development.\u003c/p\u003e\u003cp\u003eInfection is a frequent complication following surgery, with cholangitis, bacterial pneumonia, septicemia, fungal infection being the most encountered types. Among these infections, cholangitis has the highest incidence rate, ranging from 40% to 93% \u003csup\u003e[\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. It is generally believed that cholangitis shortens native liver survival in children and increases the risk of liver transplantation \u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. Studies indicate that children who experience early cholangitis have a significantly lower two-year native liver survival rate compared to those without such an occurrence \u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. However, in addition to postoperative cholangitis following BA surgery, there is a risk of other localized and systemic infections such as pneumonia and sepsis\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. Currently, there is a paucity of relevant research literature examining the impact of postoperative infections other than cholangitis on both native liver survival and mortality. This study aims to investigate the risk factors associated with post-KP infection in children with BA and assess the impact of infection on native liver survival.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1 Participants\u003c/h2\u003e\u003cp\u003e The study was approved by the Ethics Committee of the First Affiliated Hospital of Guangxi Medical University (approval number 2023-K018-01) and conducted in accordance with the ethical standards laid down in the World Medical Association\u0026rsquo;s Declaration of Helsinki. The same committee waived the requirement for the acquisition of informed consent from parents or guardian owing to the retrospective nature of the study.\u003c/p\u003e\u003cp\u003eData were accessed for research from January 2012 to August 2022 at the First Affiliated Hospital of Guangxi Medical University. The retrospective single-center cohort study conducted included 404 children\u0026rsquo;s patients with BA who underwent Kasai procedure (KP). The inclusion criteria for BA require confirmation through surgical exploration, which can be classified into three types according to the Kasai classification system. Type I includes dendritic and cloudy common bile duct atresia, while type II involves hepatic duct atresia. Finally, type III refers to hilar atresia or complete extrahepatic bile duct obstruction \u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. The exclusion criteria encompass the coexistence of other systemic malformations, congenital genetic metabolic disorders, congenital immunodeficiency syndromes or inflammatory conditions in conjunction with BA. Children with BA who developed infection before surgery.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2 Definition of pertinent clinical indicators and diagnostic criteria\u003c/h2\u003e\u003cp\u003e(1) Infection: Infection refers to cholangitis, sepsis and respiratory infections. Early infection is defined as an infection occurring within 1 month after KP. \"Late-onset infection\" refers to an infection that occurs more than 1 month, and within 12 months for infections other than cholangitis, following the performance of KP. In the case of cholangitis, it is defined as an infection occurring in any time after KP. Frequent infections are those that occur three or more times within six months, while sporadic infections occur less than three times within six months\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003e(2) Cholangitis: Symptoms of a cholangitis attack include unexplained fever, worsening or receding yellowing of the skin and sclera, lighter stool color or reappearance of clay-colored stools, increased levels of serum bilirubin (total and direct), as well as significant increases in leukocytes, neutrophils, C-reactive protein and procalcitonin according to blood tests \u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003e(3) Native liver survival: The starting point was the time after KP, and the end point was the period of liver decompensation or before liver transplantation or death due to liver failure.\u003c/p\u003e\u003cp\u003e\u003cb\u003e2.3 Cohorts were stratified for analysis according to the presence or absence of infection as an exposure variable.\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe clinical data collected in this study encompassed demographic information such as gender and age at the time of operation, details regarding occurrence of postoperative infection, glucocorticoid usage, results from blood routine examination, liver function tests including total bilirubin (TBIL), direct bilirubin (DBIL), γ-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acids (TBA), and albumin (ALB) levels.\u003c/p\u003e\u003cp\u003eThe subjects were categorized into two groups based on the presence or absence of infection: non-infected group and infected group. Subsequently, subgroup analysis was conducted according to the type of infection, which included bacterial infection group, fungal infection group, and mixed infection group. According to the site of infection, the cohort was categorized into groups based on biliary tract infection, pulmonary infection, and systemic infection. The classification was also done according to the timing of infection: early-onset infection group, late-onset infection group, and recurrent infection group. The risk factors for postoperative infections in patients with BA and the incidence of infections at different sites were analyzed. Additionally, correlation analyses were performed to investigate the effects of age at operation, surgical approach, antibiotic and glucocorticoid duration, jaundice clearance rate, liver fibrosis, and native liver survival.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.4 Follow-up and prognostic assessment\u003c/h2\u003e\u003cp\u003eBiochemical indicators such as liver function was followed up regularly 4 weeks, 8 weeks, 12 weeks, 6 months, and 12 months after KP. and the follow-up end points were liver transplantation (decompensation of liver failure), or death due to the liver failure.\u003c/p\u003e\u003cp\u003eSurvival analysis: Short-term survival: the native liver survival time was \u0026lt;\u0026thinsp;6 months; Intermediate survival: the native liver survival time was between 6 months to two years; Long-term survival: the native liver survival time was \u0026gt;\u0026thinsp;5 years.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.5 Statistical analysis\u003c/h2\u003e\u003cp\u003eSPSS 27.0 software was utilized for conducting statistical analysis on the data. The mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\stackrel{-}{X}\\)\u003c/span\u003e\u003c/span\u003e\u0026plusmn;SD) was employed for measuring data that exhibited a normal distribution, while the median [P50 (P25, P75)] was used for measuring data that did not conform to a normal distribution. A two-independent sample t-test was conducted to compare between groups. The binary categorical variable was presented as percentages, and inter-group comparisons were conducted using either the chi-square test or Fisher's exact test. The Kaplan-Meier method was used to estimate the native liver survival. The log-rank test was employed to analyze differences in survival rates among different groups, while binary logistic regression was utilized to identify the independent risk factors for infections. A \u003cem\u003eP\u003c/em\u003e value of less than 0.05 indicated a statistically significant difference.\u003c/p\u003e\u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e3.1 Demographic data of the cohort\u003c/h2\u003e\u003cp\u003eFrom January 2012 to August 2022, a total of 404 children with BA who underwent KP met the inclusion criteria. In the infection group, there were 240 BA patients, comprising of 118 (49.2%) male and 122 (50.8%) female. The age range for KP was between 39 to 248 days, with a median age of [75.5(63.0, 92.8)] days. The height ranged from 41cm to 75cm, with an average of 57.58\u0026thinsp;\u0026plusmn;\u0026thinsp;4.03 cm, while the weight ranged from 2.2 kg to 9 kg, with an average of 5.09\u0026thinsp;\u0026plusmn;\u0026thinsp;0.87 kg. BA type I accounted for only12 cases (5%), type II accounted for nine cases (3.8%), and type III accounted for most 219 cases in total (91.2%). In the non-infected group, there were 164 BA patients, comprising of 92 (56.1%) males and 72 (43.9%) females. The age at KP ranged from 40 to 210 days, with a median age of [75.0(62.0, 93.0)] days. The height ranged from 45 cm to 70 cm, with an average of 57.24\u0026thinsp;\u0026plusmn;\u0026thinsp;3.90 cm, while the weight ranged from 2.1 kg to 8.5 kg, averaging at 4.88\u0026thinsp;\u0026plusmn;\u0026thinsp;0.94 kg. BA type I was observed in 8 cases (4.9%) while type II and III were seen in 11 (6.7%) and one145(88.4%) cases respectively. There were no significant differences in gender, age of operation, height and type of BA between the two groups, all \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05. Interestingly, the infected group exhibited a significantly higher weight compared to the non-infected group, with a statistically significant difference between the two groups, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of demographic characteristics data\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"11\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eGroups\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003eGender\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eAge of operation\u003c/p\u003e\u003cp\u003e(Day)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eWeight (kg)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eHeight (cm)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eLiver fibrosis score\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eType I\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eType II\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eType II\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMale (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMale (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNon-infected group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e161\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e89(55.28)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e72 (44.72)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e77.0(63.0,91.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4.88\u0026thinsp;\u0026plusmn;\u0026thinsp;0.94\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e57.24\u0026thinsp;\u0026plusmn;\u0026thinsp;3.90\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2.74\u0026thinsp;\u0026plusmn;\u0026thinsp;1.15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e145\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInfected group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e240\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e118 (49.17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e122 (50.83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e75.0(62.0,93.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e5.09\u0026thinsp;\u0026plusmn;\u0026thinsp;0.87\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e57.58\u0026thinsp;\u0026plusmn;\u0026thinsp;4.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2.87\u0026thinsp;\u0026plusmn;\u0026thinsp;1.20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e219\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eχ2/t/Z\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003e4.235\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-0.175\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-2.253\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-0.818\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-1.084\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c11\" namest=\"c9\"\u003e\u003cp\u003e1.181\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003e0.120\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.861\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.025\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.414\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.279\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c11\" namest=\"c9\"\u003e\u003cp\u003e0.404\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003e3.2 Etiological composition of infection and outcome\u003c/h2\u003e\u003cp\u003eA total of 240 cases were included in the infection group, of which 88 cases were detected positive pathogenic microorganisms, the positive rate of pathogen detection was 36.67%. Among the 88 cases, 58 (65.9%) were positive in blood culture, 32 (36.4%) in sputum culture, 5 in urine culture, 3 in ascites culture and 1 in bile culture.\u003c/p\u003e\u003cp\u003eThere were 27 fatalities attributed to infection, resulting in an infection-related mortality rate of 11.25% (27/240). Among them, 6 cases of cholangitis, and 21 cases of mixed infections.There were 5 cases of fungal infection among the mixed infections.Positive blood cultures were identified in 10 patients, including Klebsiella pneumoniae\u0026thinsp;+\u0026thinsp;Enterococcus faecalis (1case), Acinetobacter baumannii (2 cases), Enterobacter cloacae (1 case), Escherichia coli (3 cases), and Enterococcus faecalis (3 cases). Additionally, positive sputum cultures were found in 3 patients: Acinetobacter baumannii (1 case), Acinetobacter baumannii\u0026thinsp;+\u0026thinsp;Candida albicans (1 case) and Stenotrophomonas maltophilia (1case). Sepsis was present in 16 fatal cases (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCommon infectious bacteria and drug susceptibility results\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePathogens of infection\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNumber of cases\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSource of culture specimen\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDrug-sensitivity\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKlebsiella pneumoniae\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSputum, blood, urine, ascites\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCiprofloxacin, Levofloxacin, Amikacin, gentamicin\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEscherichia coli\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eBlood and sputum\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMeropenem, imipenem, Amikacin\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEnterococcus faecium\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eBlood\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eVancomycin, Linezolid\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBaumanii\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eBlood and sputum\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTigecycline\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEnterobacter cloacae\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eBlood\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMeropenem, imipenem, ciprofloxacin\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCandida albicans\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSputum, blood, urine, ascites\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eVoriconazole, Diflucan\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEnterococcus faecalis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eBlood\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eVancomycin, Linezolid, Levofloxacin\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStenotrophomonas maltophilia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eBlood, sputum, bile\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLevofloxacin, cotrimoxazole, ceftazidime\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKlebsiella oxytoca\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eBlood\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCefoperazone sulbactam, ceftriaxone, meropenem, imipenem\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSerratia marcescens\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eBlood, sputum\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCefoperazone sulbactam, Ceftriaxone, piperacillin tazobactam, meropenem, imipenem\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePseudomonas aeruginosa\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eBlood, sputum\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMeropenem, imipenem, piperacillin tazobactam, cefoperazone sulbactam\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMoraxella osloensis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eBlood\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eErythromycin\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCandida parapsilosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eBlood\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDrug sensitivity test was not performed\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCandida tropicalis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSputum\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDrug sensitivity test was not performed\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003e3.3 The impact of infection on prognosis\u003c/h2\u003e\u003cdiv id=\"Sec11\" class=\"Section3\"\u003e\u003ch2\u003e3.3.1 Effects of infection on native liver survival\u003c/h2\u003e\u003cp\u003eAmong the 404 cases of follow-up, the native liver survival ranged from 0.2 to 14.2 years, with an average duration of 1.99 years. The mean native liver survival was 1.57\u0026thinsp;\u0026plusmn;\u0026thinsp;1.70 years in the infection group, while the mean native liver survival was 2.60\u0026thinsp;\u0026plusmn;\u0026thinsp;2.95 years in the non-infection group. Notably, there was a statistically significant difference between the native liver survival rates of infected and non-infected groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe 2-year native liver survival rate was 41.46% (68/164) in the non-infected group and 25.42% (61/240) in the infected group, (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Notably, the native liver survival was significantly lower in the infected group compared to the non-infected group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Subgroup analysis was performed among the 27 infection deaths showed that the native liver survival in the fungal infection group was significantly lower than the non-fungal infection group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.013).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section3\"\u003e\u003ch2\u003e3.3.2 Effects of infection on liver function\u003c/h2\u003e\u003cp\u003eThe levels of ALB in the infected group were significantly lower post-operation compared to those in the non-infected group during the 4 weeks, 8 weeks, 12 weeks, 6 months and 12 months followed up (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.026). The levels of TBIL and DBIL in the infected group were significantly higher post-operation compared to those in the non-infected group (all \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01). There was no statistically significant disparity in ALT, AST, GGT and TBA between the infected and non-infected group at the one-year post operation (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05), Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eInfectious complications are common following KP for BA. Typically, these include cholangitis, pneumonia, and sepsis. Pathogens include bacteria, cytomegalovirus, Epstein Barr virus, and fungal infections. The highest incidence among them is cholangitis, accounting for 40%-93% \u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. In this study, the overall infection rate was found to be 59.4%, with cholangitis accounting for a significant proportion at 90.8%. These findings align closely with previous studies conducted in the field \u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. In this study, 88 (36.7%) of infection patients were identified as pathogenic bacterial infections. The most prevalent pathogens identified were Escherichia coli and Enterococcus faecium, followed by Klebsiella pneumoniae and Enterobacter cloformis. These findings are consistent with previous research conducted the previous study \u003csup\u003e[\u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. In this study, most of the postoperative cases were treated with glucocorticoids, and the incidence of fungal infection was 10.4%. Results showed that glucocorticoid use more than 4 weeks was a risk factor for infections, especially fungal infections. The main pathogen of fungal infection is Candida, which is sensitive to drugs such as voriconazole and fluconazole. These findings are consistent with previous reports\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e .\u003c/p\u003e\u003cp\u003eThe findings of this study indicate that the fatality rate following infection is as high as 11.15%, with sepsis being the primary cause of mortality. The mortality rate following sepsis was found to be 59.26%, indicating a higher fatality rate associated with this condition. Therefore, early intervention and aggressive antimicrobial therapy can reduce the risk of death. However, the positive rate of traditional etiological detection methods, including blood culture, was very low. In this study, the positive rate of etiological detection was only 36.67%. With the development of science and technology, metagenomic next generation sequencing (mNGS) can be utilized in post-operative children with BA to enhance the positive detection rate of infectious pathogens \u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. Early detection and standardized treatment should be implemented to prolong the native liver survival.\u003c/p\u003e\u003cp\u003eThe impact of infection on liver function primarily manifests as a reduction in bilirubin clearance. Our study found that the jaundice clearance rate was 44.8% among non-infected patients, compared to 31.3% among infected patients. Cholangitis and frequent cholangitis exert the most significant impact on jaundice clearance, which is in line with the findings of the previous study \u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e. The early clearance of bilirubin can ameliorate hepatocyte damage caused by cholestasis and retard the progression of cirrhosis \u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e. The findings of this study demonstrate that cholangitis and recurrent cholangitis predominantly impact TBA and GGT levels, while albumin is affected in the context of any infection. Given that albumin serves as a marker for liver synthesis, it can be inferred that any infection will have an impact on hepatic synthesis. A study showed that achieving a postoperative bile acid level of less than 40 \u0026micro;mol/L could lead to a favorable prognosis \u003csup\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e. Therefore, early identification of postoperative infection risk and prompt and appropriate anti-infective therapy can enhance the prognosis of BA.\u003c/p\u003e\u003cp\u003eThe presence of infection has a significant impact on the postoperative native liver survival of BA, as evidenced by a 2-year native liver survival rate of 40.4% for non-infected patients and only 25.4% for infected patients. The native liver survival in patients with fungal infection and frequent cholangitis was significantly shortened. These findings are in line with the notion that infection can impede jaundice clearance and hypoalbuminemia may result from reduced liver synthesis. As cholestasis cannot be promptly resolved, severe liver cell damage ensues, thereby compromising native liver survival.\u003c/p\u003e\u003cp\u003eThis study found that patients with a larger body weight or body mass index (BMI) are more likely to develop postoperative infections, but the number of infections is not high. Body weight is the most important and sensitive indicator reflecting the physical growth of children, and it is a comprehensive reflection of both short-term and long-term nutritional status. The body mass index (BMI)\u0026thinsp;=\u0026thinsp;body weight (kg) / height (m)\u0026sup2;. It can compare weight differences under the same height condition, effectively eliminating the influence of physical development differences caused by factors such as gender, development level, genetics, and ethnic differences before puberty. It is a sensitive indicator for judging emaciation in children and reflects the recent nutritional status \u003csup\u003e[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/sup\u003e. Some studies have shown that the degree of preoperative malnutrition is positively correlated with the occurrence of cholangitis after biliary atresia surgery \u003csup\u003e[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/sup\u003e. Since body weight is only one of the indicators for evaluating nutritional status, it cannot fully illustrate the true nutritional status of children before surgery. The small intestine is the largest digestive and absorptive organ in the human body, and its length is related to the individual's own body length \u003csup\u003e[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/sup\u003e. Children with a larger body weight generally have a slightly longer height, so the length of their small intestine is longer than that of those with a smaller body weight. The length of the intestinal loop after Kasai surgery may be longer in children with a larger body weight compared to those with a smaller body weight, and the length and area of the small intestine for absorbing nutrients are larger. Due to the inconsistent growth and development rates of the small intestine and the mesentery, the excessively long jejunal biliary limb in children with good nutritional status is more likely to develop complications such as intestinal volvulus, intestinal obstruction, and cholestasis, increasing the occurrence of cholangitis. Secondly, in children with a longer intestinal loop, the risks of upward infection of intestinal bacteria and reflux of intestinal contents increase, both of which increase the incidence of cholangitis. However, the probability of frequent infections in children with a larger body weight is not high, which may be related to the nutritional status of the children \u003csup\u003e[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/sup\u003e. In this study, the relatively large body weight of the children at the time of surgery may also be related to the relatively large age at the time of surgery. China is a developing country, and there is an imbalance in the development of economic and health levels. Guangxi is a relatively underdeveloped region in the western part of China. Children seek medical treatment relatively late, so the age at the time of surgery is relatively large.\u003c/p\u003e\u003cp\u003eIn conclusion infection significantly reduces the jaundice clearance rate, albumin levels and native liver survival in BA after KP.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of Interest Statement:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the authors declare that there is no conflict of interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; Contributions:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eXY MENG contributed to data collection, statistically analyzed, and drafting of the paper. L HUANG and X YUN contributed the sample collection and revision of the paper. Q TANG and XQ CHEN contributed the conception and design of study and revised the final paper. All authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eApproval Committee or the Internal Review Board (IRB)\u003c/strong\u003e\u003cstrong\u003e：\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethics Committee of the First Affiliated Hospital of Guangxi Medical University (approval number 2023-K018-01) and conducted in accordance with the ethical standards laid down in the World Medical Association\u0026rsquo;s Declaration of Helsinki. The same committee waived the requirement for the acquisition of informed consent from parents or guardian owing to the retrospective nature of the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003cstrong\u003e：\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the Excellent Medical Talents Training Program of the First Affiliated Hospital of Guangxi Medical University, Guangxi Natural Science Foundation (no. 2024GXNSFAA010055), Guangxi Clinical Medical Research Center for Pediatric Diseases (Guike AD22035121), Middle/Young aged Teachers\u0026apos; Research Ability Improvement Project of Guangxi Higher Education (2024KY0093) , Clinical Research \u0026quot;Climbing\u0026quot; Program of the First Affiliated Hospital of Guangxi Medical University (YYZS2023011), Difficult and Critical illness Center, Pediatric Clinical Medical Research Center of Guangxi (Gui Ke AD22035219), and the Key Laboratory of Children\u0026apos;s Disease Research in Guangxi\u0026rsquo;s Colleges and Universities, Education Department of Guangxi Zhuang Autonomous Region.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish declaration:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors approved the final submitted manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during this study are included in this article and supporting information. Further inquiries can be directed to the corresponding author.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eNomden M, van Wessel DBE, Ioannou S, et al. A Higher Incidence of Isolated Biliary Atresia in Rural Areas: Results From an Epidemiological Study in The Netherlands[J]. J Pediatr Gastroenterol Nutr. 2021;72(2):202\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSchreiber RA, Harpavat S, Hulscher JBF et al. Biliary Atresia in 2021: Epidemiology, Screening and Public Policy[J]. J Clin Med. 2022;11(4).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCavallo L, Kovar EM, Aqul A, et al. The Epidemiology of Biliary Atresia: Exploring the Role of Developmental Factors on Birth Prevalence[J]. J Pediatr. 2022;246:89\u0026ndash;94. e2.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAl-Hussaini A, Abanemai M, Alhebbi H, et al. 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Indian J Gastroenterol. 2023.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiu J, Dong R, Chen G, et al. Risk factors and prognostic effects of cholangitis after Kasai procedure in biliary atresia patients: A retrospective clinical study[J]. J Pediatr Surg. 2019;54(12):2559\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLuo Y, Zheng S. Current concept about postoperative cholangitis in biliary atresia[J]. World J Pediatr. 2008;4(1):14\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWu ET, Chen HL, Ni YH, et al. Bacterial cholangitis in patients with biliary atresia: impact on short-term outcome[J]. Pediatr Surg Int. 2001;17(5\u0026ndash;6):390\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTriggs ND, Beer S, Mokha S, et al. Central line-associated bloodstream infection among children with biliary atresia listed for liver transplantation[J]. World J Hepatol. 2019;11(2):208\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVij M, Rela M. Biliary atresia: pathology, etiology and pathogenesis[J]. Future Sci OA. 2020;6(5):FSO466.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSection of Hepatobiliary Surgery, Branch of Pediatric Surgery, Chinese Medical Association. Section of Pediatric Hepatic Transplantation, Branch of Organ Transplantation, Chinese Medical Doctor Association. [Guidelines for Diagnosing and Treating Biliary Atresia (2018 Edition)] [J]. J Clin Hepatobiliary Dis. 2019;35(11):2435\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSection of Hepatobiliary Surgery, Branch of Pediatric Surgery, Chinese Medical Association. [Expert Consensus on Diagnosing and Treating Cholangitis after Kasai Operation for Biliary Atresia (2022 Edition)]. Chin J Pediatr Surg. 2022;43(9):769\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eXie E, Sun C, Dong C, et al. Impact of allograft types on outcomes after pediatric liver transplantation due to biliary atresia[J]. Pediatr Transpl. 2022;26(7):e14342.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHamdy GE, Yasmin K, Abdel-Hameed ST et al. Short- and long-term outcomes after Kasai operation for type III biliary atresia: Twenty years of experience in a single tertiary Egyptian center-A retrospective cohort study[J]. Annals Med Surg. 2021;62.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChen X, Su HX, Chen XQ. [Distributions of pathogenic bacteria and drug sensitivity in cholangitis after hepatico-portoenterostomy for biliary atresia]. J Practical Med. 2018;34(3):435\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhang Kz JZ. 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Serum bile acids as a prognostic biomarker in biliary atresia following Kasai portoenterostomy[J]. Hepatology. 2023;77(3):862\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang Li C, Yajun Z, Tingchong, et al. [Physical Development Z-scores of Children with Autologous Liver Survival after Kasai Operation for Biliary Atresia][J]. Chin J Pediatr Surg. 2016;37(5):331\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAris Izzuddin M, Chen Ling-Wei TM, Thway et al. Body mass index trajectories in the first two years and subsequent childhood cardio-metabolic outcomes: a prospective multi-ethnic Asian cohort study[J]. Sci Rep, 2017, 7(1).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChen Xiaoai Y, Jixin FJ. [Study on the Influence of Preoperative Nutritional Status on Cholangitis after Biliary Atresia Surgery][J]. 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J Clin Pediatr Surg. 2020;19(9):851\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Biliary atresia, Infect, Cholangitis, Liver function, Infants","lastPublishedDoi":"10.21203/rs.3.rs-7625443/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7625443/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eBesides to cholangitis, there are few reports on the influence of other infections post-Kasai procedure (KP) in biliary atresia (BA). The study is to investigate the prognosis associated with post-Kasai procedure (KP) infection.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis retrospective study included children with BA who underwent KP. Postoperative infection was the primary exposure variable of interest in this cohort. The primary outcome measure was post-operative native liver survival, while the secondary outcome measure was mortality attributed to infection.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003e1. A total of 404 cases included in the study. There were no significant differences in gender, age at operation, or gestational age between the two groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The native liver survival was 2.60\u0026thinsp;\u0026plusmn;\u0026thinsp;2.95 years in the non-infected group, whereas it was reduced to 1.57\u0026thinsp;\u0026plusmn;\u0026thinsp;1.70 years in the infected group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Early-onset infection primarily impacts bilirubin clearance, resulting in delayed clearance of bilirubin (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003ePostoperative infection in biliary atresia delays bilirubin clearance and reduces native liver survival.\u003c/p\u003e","manuscriptTitle":"Postoperative Infection in Biliary Atresia Patients Reduces Early Bilirubin Clearance and Native Liver Survival: A Single - Center Retrospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-29 04:46:02","doi":"10.21203/rs.3.rs-7625443/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-11-23T13:13:10+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-21T04:34:02+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-20T20:05:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"322078067563033365577418729848381520281","date":"2025-11-19T10:38:49+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-18T11:34:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"286593131081625066798972665975377131050","date":"2025-11-18T09:01:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"177371005220310109171617255571133565515","date":"2025-11-18T05:24:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"153617132655199999542777318805052523050","date":"2025-11-18T03:59:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"62663634497951427159685420995719116365","date":"2025-11-17T23:43:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"244644806210566556059586184962667499828","date":"2025-10-17T00:59:28+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-14T23:55:42+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-10-07T05:05:07+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-06T02:12:31+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-06T02:11:28+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2025-09-16T03:36:48+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"118c75ad-d19d-4b92-932d-fa95ee9c9713","owner":[],"postedDate":"October 29th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-09T16:08:15+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-29 04:46:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7625443","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7625443","identity":"rs-7625443","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}