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Open AccessArticle

Pediatric Liver and Transplant Surgery: Results of an International Survey and Expert Consensus Recommendations

by Caroline P. Lemoine, Omid Madadi-Sanjani, Claus Petersen, Christophe Chardot, Jean de Ville de Goyet and Riccardo Superina

J. Clin. Med. 2023, 12(9), 3229; https://doi.org/10.3390/jcm12093229 - 30 Apr 2023

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Abstract

Background: Pediatric liver surgery is a complex and challenging procedure and can be associated with major complications, including mortality. Best practices are not established. The aims of this study were to evaluate surgeons’ individual and institutional practices in pediatric liver surgery and make [...] Read more.

Background: Pediatric liver surgery is a complex and challenging procedure and can be associated with major complications, including mortality. Best practices are not established. The aims of this study were to evaluate surgeons’ individual and institutional practices in pediatric liver surgery and make recommendations applicable to the management of children who require liver surgery. Methods: A web-based survey was developed, focusing on the surgical management of children with liver conditions. It was distributed to 34 pediatric surgery faculty members of the Biliary Atresia and Related Disorders (BARD) consortium and 28 centers of the European Reference Network—Rare Liver. Using the Delphi method, a series of questions was then created to develop ideas about potential future developments in pediatric liver surgery. Results: The overall survey response rate was 70.6% (24/34), while the response rate for the Delphi questionnaire was 26.5% (9/34). In centers performing pediatric liver surgery, most pediatric subspecialties were present, although pediatric oncology was the least present (79.2%). Nearly all participants surveyed agreed that basic and advanced imaging modalities (including ERCP) should be available in those centers. Most pediatric liver surgeries were performed by pediatric surgeons (69.6%). A majority of participants agreed that centers treating pediatric liver tumors should include a pediatric transplant program (86%) able to perform technical variant grafts and living donor liver transplantation. Fifty-six percent of responders believe pediatric liver transplantation should be performed by specialized pediatric surgeons. Conclusion: Pediatric liver surgery should be performed by specialized pediatric surgeons and should be centralized in regional centers of excellence where all pediatric subspecialists are present. Pediatric hepatobiliary and transplant training needs to be better promoted amongst pediatric surgery fellows to increase this subspecialized workforce. Full article

(This article belongs to the Special Issue Biliary Atresia: Aetiology, Diagnosis and Treatment)

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15 pages, 29277 KiB

Open AccessArticle

Neonatal Hepatic Myeloid Progenitors Expand and Propagate Liver Injury in Mice

by Anas Alkhani, Cathrine Korsholm, Claire S. Levy, Sarah Mohamedaly, Caroline C. Duwaerts, Eric M. Pietras and Amar Nijagal

J. Clin. Med. 2023, 12(1), 337; https://doi.org/10.3390/jcm12010337 - 01 Jan 2023

Cited by 2 | Viewed by 2034

Abstract

Background: Biliary atresia (BA) is a progressive pediatric inflammatory disease of the liver that leads to cirrhosis and necessitates liver transplantation. The rapid progression from liver injury to liver failure in children with BA suggests that factors specific to the perinatal hepatic environment [...] Read more.

Background: Biliary atresia (BA) is a progressive pediatric inflammatory disease of the liver that leads to cirrhosis and necessitates liver transplantation. The rapid progression from liver injury to liver failure in children with BA suggests that factors specific to the perinatal hepatic environment are important for disease propagation. Hematopoietic stem and progenitor cells (HSPCs) reside in the fetal liver and are known to serve as central hubs of inflammation. We hypothesized that HSPCs are critical for the propagation of perinatal liver injury (PLI). Methods: Newborn BALB/c mice were injected with rhesus rotavirus (RRV) to induce PLI or with PBS as control. Livers were compared using histology and flow cytometry. To determine the effects of HSPCs on PLI, RRV-infected neonatal mice were administered anti-CD47 and anti-CD117 to deplete HSPCs. Results: PLI significantly increased the number of common myeloid progenitors and the number of CD34⁺ hematopoietic progenitors. Elimination of HSPCs through antibody-mediated myeloablation rescued animals from PLI and significantly increased survival (RRV+isotype control 36.4% vs. RRV+myeloablation 77.8%, Chi-test = 0.003). Conclusions: HSPCs expand as a result of RRV infection and propagate PLI. Targeting of HSPCs may be useful in preventing and treating neonatal inflammatory diseases of the liver such as BA. Full article

(This article belongs to the Special Issue Biliary Atresia: Aetiology, Diagnosis and Treatment)

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10 pages, 3327 KiB

Open AccessArticle

The Impact of a CMV Infection on the Expression of Selected Immunological Parameters in Liver Tissue in Children with Biliary Atresia

by Maria Janowska, Joanna B. Bierła, Magdalena Kaleta, Aldona Wierzbicka-Rucińska, Piotr Czubkowski, Ewelina Kanarek, Bożena Cukrowska, Joanna Pawłowska and Joanna Cielecka-Kuszyk

J. Clin. Med. 2022, 11(24), 7269; https://doi.org/10.3390/jcm11247269 - 07 Dec 2022

Cited by 2 | Viewed by 891

Abstract

The pathogenesis of biliary atresia (BA) is still not clear. The aim of this study was to evaluate the expression of selected immunological parameters in liver tissue in BA children based on CMV/EBV infection status. Eight of thirty-one children with newly diagnosed BA [...] Read more.

The pathogenesis of biliary atresia (BA) is still not clear. The aim of this study was to evaluate the expression of selected immunological parameters in liver tissue in BA children based on CMV/EBV infection status. Eight of thirty-one children with newly diagnosed BA were included in this prospective study and assigned to two groups (I with active infection, II without active or past infection). All studies were performed on surgical liver biopsies. To visualize CD8+ T cells and CD56 expression, immunohistochemical staining was performed. The viral genetic material in the studied groups was not found, but CMV infection significantly affected the number of CD8+ lymphocytes in both the portal area and the bile ducts. The average number of CD8+ cells per mm² of portal area in Groups I and II was 335 and 200 (p = 0.002). The average number of these cellsthat infiltrated the epithelium of the bile duct per mm² in Group I and II was 0.73 and 0.37 (p = 0.0003), respectively. Expression of CD56 in the bile ducts corresponded to the intensity of the inflammatory infiltrate of CD8+ cells. Our results suggest that active CMV infection induces an increased infiltration of CD8+ lymphocytes, which could play a role in BA immunopathogenesis. Increased CD56 expression can be a sign of a newly formed bile structure often without lumen, suggesting inhibition of the maturation process in BA. Full article

(This article belongs to the Special Issue Biliary Atresia: Aetiology, Diagnosis and Treatment)

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9 pages, 261 KiB

Open AccessArticle

Surgical and Medical Aspects of the Initial Treatment of Biliary Atresia: Position Paper

by Mark Davenport, Omid Madadi-Sanjani, Christophe Chardot, Henkjan J. Verkade, Saul J. Karpen and Claus Petersen

J. Clin. Med. 2022, 11(21), 6601; https://doi.org/10.3390/jcm11216601 - 07 Nov 2022

Cited by 2 | Viewed by 1569

Abstract

Biliary atresia, a fibro-obliterative disease of the newborn, is usually initially treated by Kasai portoenterostomy, although there are many variations in technique and different options for post-operative adjuvant medical therapy. A questionnaire on such topics (e.g., open vs. laparoscopic; the need for liver [...] Read more.

Biliary atresia, a fibro-obliterative disease of the newborn, is usually initially treated by Kasai portoenterostomy, although there are many variations in technique and different options for post-operative adjuvant medical therapy. A questionnaire on such topics (e.g., open vs. laparoscopic; the need for liver mobilisation; use of post-operative steroids; use of post-operative anti-viral therapy, etc.) was circulated to delegates (n = 43) of an international webinar (Biliary Atresia and Related Diseases—BARD) held in June 2021. Respondents were mostly European, but included some from North America, and represented 18 different countries overall. The results of this survey are presented here, together with a commentary and review from an expert panel convened for the meeting on current trends in practice. Full article

(This article belongs to the Special Issue Biliary Atresia: Aetiology, Diagnosis and Treatment)

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Open AccessArticle

Identification of Early Clinical and Histological Factors Predictive of Kasai Portoenterostomy Failure

by Caroline P. Lemoine, Hector Melin-Aldana, Katherine A. Brandt and Riccardo Superina

J. Clin. Med. 2022, 11(21), 6523; https://doi.org/10.3390/jcm11216523 - 03 Nov 2022

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Abstract

Background: It is impossible to predict which patients with biliary atresia (BA) will fail after Kasai portoenterostomy (KPE). We evaluated the predictive nature of pre-KPE clinical and histological factors on transplant-free survival (TFS) and jaundice clearance. Methods: A retrospective review of patients who [...] Read more.

Background: It is impossible to predict which patients with biliary atresia (BA) will fail after Kasai portoenterostomy (KPE). We evaluated the predictive nature of pre-KPE clinical and histological factors on transplant-free survival (TFS) and jaundice clearance. Methods: A retrospective review of patients who received a KPE at our institution (1997–2018) was performed. Primary outcomes were two-year TFS, five-year TFS, and jaundice clearance 3 months after KPE. p < 0.05 was considered significant. Results: Fifty-four patients were included in this study. The two-year TFS was 35.1%, five-year TFS was 24.5%, and 37% patients reached a direct bilirubin (DB) ≤ 2.0 mg/dL 3 months post KPE. The median age at biopsy was younger in the five-year TFS (39.0 (24.5–55.5) vs. 56.0 days (51.0–67.0), p = 0.011). Patients with DB ≤ 1.0 mg/dL 3 months after KPE were statistically younger at biopsy (DB ≤ 1.0 44.0 (26.0–56.0) vs. DB > 1.0 56.0 days (51.0–69.0), p = 0.016). Ductal plate malformation was less frequent in the five-year TFS (16/17, 94.1%, vs. 1/17, 5.9%, p = 0.037). Portal fibrosis (19/23, 82.6%, vs. 4/23, 17.4%, p = 0.028) and acute cholangitis (6/7, 85.7%, vs. 1/7, 14.3%, p = 0.047) occurred less frequently in two-year TFS. Conclusion: Older age at biopsy, acute cholangitis, portal fibrosis, and ductal plate malformation were associated with lower native liver survival. Evaluation in a larger study population is needed to validate these results. Full article

(This article belongs to the Special Issue Biliary Atresia: Aetiology, Diagnosis and Treatment)

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12 pages, 2136 KiB

Open AccessArticle

Hepatic Ly6C^Lo Non-Classical Monocytes Have Increased Nr4a1 (Nur77) in Murine Biliary Atresia

by Sarah Mohamedaly, Claire S. Levy, Cathrine Korsholm, Anas Alkhani, Katherine Rosenberg, Judith F. Ashouri and Amar Nijagal

J. Clin. Med. 2022, 11(18), 5290; https://doi.org/10.3390/jcm11185290 - 08 Sep 2022

Cited by 1 | Viewed by 1938

Abstract

Biliary atresia (BA) is a rapidly progressive perinatal inflammatory disease, resulting in liver failure. Hepatic Ly6C^Lo non-classical monocytes promote the resolution of perinatal liver inflammation during rhesus rotavirus-mediated (RRV) BA in mice. In this study, we aim to investigate the effects of [...] Read more.

Biliary atresia (BA) is a rapidly progressive perinatal inflammatory disease, resulting in liver failure. Hepatic Ly6C^Lo non-classical monocytes promote the resolution of perinatal liver inflammation during rhesus rotavirus-mediated (RRV) BA in mice. In this study, we aim to investigate the effects of inflammation on the transcription factor Nr4a1, a known regulator of non-classical monocytes. Nr4a1-GFP reporter mice were injected with PBS for control or RRV within 24 h of delivery to induce perinatal liver inflammation. GFP expression on myeloid immune populations in the liver and bone marrow (BM) was quantified 3 and 14 days after injection using flow cytometry. Statistical significance was determined using a student’s t-test and ANOVA, with a p-value < 0.05 for significance. Our results demonstrate that non-classical monocytes in the neonatal liver exhibit the highest mean fluorescence intensity (MFI) of Nr4a1 (Ly6C^Lo MFI 6344 vs. neutrophils 3611 p < 0.001; macrophages 2782; p < 0.001; and Ly6C^Hi classical monocytes 4485; p < 0.0002). During inflammation, hepatic Ly6C^Lo non-classical monocytes showed a significant increase in Nr4a1 expression intensity from 6344 to 7600 (p = 0.012), while Nr4a1 expression remained unchanged on the other myeloid populations. These findings highlight the potential of using Nr4a1 as a regulator of neonatal hepatic Ly6C^Lo non-classical monocytes to mitigate perinatal liver inflammation. Full article

(This article belongs to the Special Issue Biliary Atresia: Aetiology, Diagnosis and Treatment)

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13 pages, 897 KiB

Open AccessArticle

Primary Liver Transplantation vs. Transplant after Kasai Portoenterostomy for Infants with Biliary Atresia

by Caroline P. Lemoine, John P. LeShock, Katherine A. Brandt and Riccardo Superina

J. Clin. Med. 2022, 11(11), 3012; https://doi.org/10.3390/jcm11113012 - 26 May 2022

Cited by 6 | Viewed by 1849

Abstract

Introduction: Primary liver transplants (pLT) in patients with biliary atresia (BA) are infrequent, since most babies with BA undergo a prior Kasai portoenterostomy (KPE). This study compared transplant outcomes in children with BA with or without a prior KPE. We hypothesized that pLT [...] Read more.

Introduction: Primary liver transplants (pLT) in patients with biliary atresia (BA) are infrequent, since most babies with BA undergo a prior Kasai portoenterostomy (KPE). This study compared transplant outcomes in children with BA with or without a prior KPE. We hypothesized that pLT have less morbidity and better outcomes compared to those done after a failed KPE. Methods: A retrospective review of patients with BA transplanted at our institution was performed. Patients were included if they received a pLT or if they were transplanted less than 2 years from KPE. Outcomes were compared between those groups. Comparisons were also made based on era (early: 1997–2008 vs. modern: 2009–2020). p < 0.05 was considered significant. Results: Patients who received a pLT were older at diagnosis (141.5 ± 46.0 vs. KPE 67.1 ± 25.5 days, p < 0.001). The time between diagnosis and listing for transplant was shorter in the pLT group (44.5 ± 44.7 vs. KPE 140.8 ± 102.8 days, p < 0.001). In the modern era, the calculated PELD score for the pLT was significantly higher (23 ± 8 vs. KPE 16 ± 8, p = 0.022). Two waitlist deaths occurred in the KPE group (none in pLT, p = 0.14). Both the duration of transplant surgery and transfusion requirements were similar in both groups. There was a significant improvement in graft survival in transplants after KPE between eras (early era 84.3% vs. modern era 97.8%, p = 0.025). The 1-year patient and graft survival after pLT was 100%. Conclusions: Patient and graft survival after pLT are comparable to transplants after a failed KPE but pLT avoids a prior intervention. There was no significant difference in pre- or peri-transplant morbidity between groups other than wait list mortality. A multicenter collaboration with more patients may help demonstrate the potential benefits of pLT in patients predicted to have early failure of KPE. Full article

(This article belongs to the Special Issue Biliary Atresia: Aetiology, Diagnosis and Treatment)

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22 pages, 1880 KiB

Open AccessArticle

Variability of Care and Access to Transplantation for Children with Biliary Atresia Who Need a Liver Replacement

by Jean de Ville de Goyet, Toni Illhardt, Christophe Chardot, Peace N. Dike, Ulrich Baumann, Katherine Brandt, Barbara E. Wildhaber, Mikko Pakarinen, Fabrizio di Francesco, Ekkehard Sturm, Marianna Cornet, Caroline Lemoine, Eva Doreen Pfister, Ana M. Calinescu, Maria Hukkinen, Sanjiv Harpavat, Fabio Tuzzolino and Riccardo Superina

J. Clin. Med. 2022, 11(8), 2142; https://doi.org/10.3390/jcm11082142 - 12 Apr 2022

Cited by 2 | Viewed by 1978

Abstract

Background & Aims: Biliary atresia (BA) is the commonest single etiology indication for liver replacement in children. As timely access to liver transplantation (LT) remains challenging for small BA children (with prolonged waiting time being associated with clinical deterioration leading to both preventable [...] Read more.

Background & Aims: Biliary atresia (BA) is the commonest single etiology indication for liver replacement in children. As timely access to liver transplantation (LT) remains challenging for small BA children (with prolonged waiting time being associated with clinical deterioration leading to both preventable pre- and post-transplant morbidity and mortality), the care pathway of BA children in need of LT was analyzed—from diagnosis to LT—with particular attention to referral patterns, timing of referral, waiting list dynamics and need for medical assistance before LT. Methods: International multicentric retrospective study. Intent-to-transplant study analyzing BA children who had indication for LT early in life (aged < 3 years at the time of assessment), over the last 5 years (2016–2020). Clinical and laboratory data of 219 BA children were collected from 8 transplant centers (6 in Europe and 2 in USA). Results: 39 patients underwent primary transplants. Children who underwent Kasai in a specialist -but not transplant- center were older at time of referral and at transplant. At assessment for LT, the vast majority of children already were experiencing complication of cirrhosis, and the majority of children needed medical assistance (nutritional support, hospitalization, transfusion of albumin or blood) while waiting for transplantation. Severe worsening of the clinical condition led to the need for requesting a priority status (i.e., Peld Score exception or similar) for timely graft allocation for 76 children, overall (35%). Conclusions: As LT currently results in BA patient survival exceeding 95% in many expert LT centers, the paradigm for BA management optimization and survival have currently shifted to the pre-LT management. The creation of networks dedicated to the timely referral to a pediatric transplant center and possibly centralization of care should be considered, in combination with implementing all different graft type surgeries in specialist centers (including split and living donor LTs) to achieve timely LT in this vulnerable population. Full article

(This article belongs to the Special Issue Biliary Atresia: Aetiology, Diagnosis and Treatment)

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12 pages, 2224 KiB

Open AccessArticle

Features of Nodules in Explants of Children Undergoing Liver Transplantation for Biliary Atresia

by Ana M. Calinescu, Anne-Laure Rougemont, Mehrak Anooshiravani, Nathalie M. Rock, Valerie A. McLin and Barbara E. Wildhaber

J. Clin. Med. 2022, 11(6), 1578; https://doi.org/10.3390/jcm11061578 - 13 Mar 2022

Cited by 1 | Viewed by 1950

Abstract

(1) Background: In patients with biliary atresia (BA) liver nodules can be identified either by pre-transplant imaging or on the explant. This study aimed to (i) analyze the histopathology of liver nodules, and (ii) to correlate histopathology with pretransplant radiological features. (2) Methods: [...] Read more.

(1) Background: In patients with biliary atresia (BA) liver nodules can be identified either by pre-transplant imaging or on the explant. This study aimed to (i) analyze the histopathology of liver nodules, and (ii) to correlate histopathology with pretransplant radiological features. (2) Methods: Retrospective analysis of liver nodules in explants of BA patients transplanted in our center (2000–2021). Correlations with pretransplant radiological characteristics, patient age at liver transplantation (LT), time from Kasai hepatoportoenterostomy (KPE) to LT, age at KPE and draining KPE. (3) Results: Of the 63 BA-patients included in the analysis, 27/63 (43%) had nodules on explants. A majority were benign macroregenerative nodules. Premalignant (low-grade and high-grade dysplastic) and malignant (hepatocellular carcinoma) nodules were identified in 6/63 and 2/63 patients, respectively. On pretransplant imaging, only 13/63 (21%) patients had liver nodules, none meeting radiological criteria for malignancy. The occurrence of liver nodules correlated with patient age at LT (p < 0.001), time KPE-LT (p < 0.001) and draining KPE (p = 0.006). (4) Conclusion: In BA patients, pretransplant imaging did not correlate with the presence of liver nodules in explants. Liver nodules were frequent in explanted livers, whereby 25% of explants harboured malignant/pre-malignant nodules, emphasizing the need for careful surveillance in BA children whose clinical course may require LT. Full article

(This article belongs to the Special Issue Biliary Atresia: Aetiology, Diagnosis and Treatment)

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15 pages, 1957 KiB

Open AccessEditor’s ChoiceArticle

Biliary Atresia in 2021: Epidemiology, Screening and Public Policy

by Richard A. Schreiber, Sanjiv Harpavat, Jan B. F. Hulscher and Barbara E. Wildhaber

J. Clin. Med. 2022, 11(4), 999; https://doi.org/10.3390/jcm11040999 - 14 Feb 2022

Cited by 20 | Viewed by 3170

Abstract

Biliary atresia (BA) is a rare newborn liver disease with significant morbidity and mortality, especially if not recognized and treated early in life. It is the most common cause of liver-related death in children and the leading indication for liver transplantation in the [...] Read more.

Biliary atresia (BA) is a rare newborn liver disease with significant morbidity and mortality, especially if not recognized and treated early in life. It is the most common cause of liver-related death in children and the leading indication for liver transplantation in the pediatric population. Timely intervention with a Kasai portoenterostomy (KPE) can significantly improve prognosis. Delayed disease recognition, late patient referral, and untimely surgery remains a worldwide problem. This article will focus on biliary atresia from a global public health perspective, including disease epidemiology, current national screening programs, and their impact on outcome, as well as new and novel BA screening initiatives. Policy challenges for the implementation of BA screening programs will also be discussed, highlighting examples from the North American, European, and Asian experience. Full article

(This article belongs to the Special Issue Biliary Atresia: Aetiology, Diagnosis and Treatment)

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6 pages, 337 KiB

Open AccessArticle

Incidence, Impact and Treatment of Ongoing CMV Infection in Patients with Biliary Atresia in Four European Centres

by Björn Fischler, Piotr Czubkowski, Antal Dezsofi, Ulrika Liliemark, Piotr Socha, Ronald J. Sokol, Jan F. Svensson and Mark Davenport

J. Clin. Med. 2022, 11(4), 945; https://doi.org/10.3390/jcm11040945 - 11 Feb 2022

Cited by 13 | Viewed by 1845

Abstract

Cytomegalovirus (CMV) infection has been suggested to be of importance for the development and outcome of biliary atresia (BA). However, most data are only available from single centre studies. We retrospectively collected data on rates, outcomes, and treatments for ongoing CMV infection at [...] Read more.

Cytomegalovirus (CMV) infection has been suggested to be of importance for the development and outcome of biliary atresia (BA). However, most data are only available from single centre studies. We retrospectively collected data on rates, outcomes, and treatments for ongoing CMV infection at the time of Kasai portoenterostomy (KPE) from four different tertiary centres in Europe. The rate of ongoing CMV infection varied between 10–32% in the four centres. CMV positive patients were significantly older and had higher levels of several liver biochemistries at the time of KPE (p < 0.05 for all comparisons). In the largest centre, CMV infection was more common in non-Caucasians, and CMV infected patients had poorer long-term survival with native liver than CMV negative patients (p = 0.0001). In contrast, survival with native liver in the subgroup of CMV infected patients who had received antiviral treatment was similar to the CMV negative group. We conclude that ongoing CMV infection at the time of KPE occurs in a significant proportion of BA patients and that these patients seem to differ from CMV negative patients regarding age and biochemistry at the time of KPE as well as long-term survival with native liver. The latter difference may be reduced by antiviral treatment, but randomized, controlled trials are needed before such treatment can be recommended routinely. Full article

(This article belongs to the Special Issue Biliary Atresia: Aetiology, Diagnosis and Treatment)

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17 pages, 3294 KiB

Open AccessArticle

Cholangitis Definition and Treatment after Kasai Hepatoportoenterostomy for Biliary Atresia: A Delphi Process and International Expert Panel

by Ana M. Calinescu, Omid Madadi-Sanjani, Cara Mack, Richard A. Schreiber, Riccardo Superina, Deirdre Kelly, Claus Petersen and Barbara E. Wildhaber

J. Clin. Med. 2022, 11(3), 494; https://doi.org/10.3390/jcm11030494 - 19 Jan 2022

Cited by 11 | Viewed by 4058

Abstract

(1) Background: Acute cholangitis during the first year after Kasai hepatoportoenterostomy (HPE) has a negative impact on patient and native liver survival. There are no consistent guidelines for the definition, treatment, and prophylaxis of cholangitis after HPE. The aim of this study was [...] Read more.

(1) Background: Acute cholangitis during the first year after Kasai hepatoportoenterostomy (HPE) has a negative impact on patient and native liver survival. There are no consistent guidelines for the definition, treatment, and prophylaxis of cholangitis after HPE. The aim of this study was to develop definition, treatment, and prophylaxis guidelines to allow for expeditious management and for standardization in reporting. (2) Methods: the Delphi method, an extensive literature review, iterative rounds of surveys, and expert panel discussions were used to establish definition, treatment, and prophylaxis guidelines for cholangitis in the first year after HPE. (3) Results: Eight elements (pooled into two groups: clinical and laboratory/imaging) were identified to define cholangitis after HPE. The final proposed definitions for suspected and confirmed cholangitis are a combination of one element, respectively, two elements from each group; furthermore, the finding of a positive blood culture was added to the definition of confirmed cholangitis. The durations for prophylaxis and treatment of suspected and confirmed cholangitis were uniformly agreed upon by the experts. (4) Conclusions: for the first time, an international consensus was found for guidelines for definition, treatment, and prophylaxis for cholangitis during the first year after Kasai HPE. Applicability will need further prospective multicentered studies. Full article

(This article belongs to the Special Issue Biliary Atresia: Aetiology, Diagnosis and Treatment)

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9 pages, 2447 KiB

Open AccessArticle

Adjuvant Therapy with Budesonide Post-Kasai Reduces the Need for Liver Transplantation in Biliary Atresia

by Joachim F. Kuebler, Omid Madadi-Sanjani, Eva D. Pfister, Ulrich Baumann, David Fortmann, Johannes Leonhardt, Benno M. Ure, Michael P. Manns, Richard Taubert and Claus Petersen

J. Clin. Med. 2021, 10(24), 5758; https://doi.org/10.3390/jcm10245758 - 09 Dec 2021

Cited by 4 | Viewed by 2178

Abstract

Based on the hypothesis that autoimmunological factors coregulate the pathomechanism in biliary atresia (BA), adjuvant therapy with steroids has become routine, although its efficacy has never been proven. In 2010, a study on the advantages of budesonide compared to prednisolone in autoimmune hepatitis [...] Read more.

Based on the hypothesis that autoimmunological factors coregulate the pathomechanism in biliary atresia (BA), adjuvant therapy with steroids has become routine, although its efficacy has never been proven. In 2010, a study on the advantages of budesonide compared to prednisolone in autoimmune hepatitis gave rise to experimental therapy using budesonide as an adjuvant BA treatment. Ninety-five BA patients prospectively received a budesonide 2 mg/dose rectal foam daily for three months (SG). A case-matched control group (CG: 81) was retrospectively recruited. The outcome measures were survival with native liver (SNL), determined at six months and two years after the Kasai procedure. The follow-up rate was 100%. At six months, SNL was statistically not different but became so after two years (SG: 54%; CG: 32%; p < 0.001). No steroid-related side effects were observed, except for eight patients with finally caught-up growth retardation. This study demonstrates for the first time a significantly longer survival with native liver in patients with BA after adjuvant therapy. However, indication, dosage, and duration of any budesonide application is not given in neonates with BA. Hence, we suggest extending the postoperative use of budesonide in a multicenter observational study with a clearly defined follow-up protocol, particularly in terms of potentially underestimated side effects. Full article

(This article belongs to the Special Issue Biliary Atresia: Aetiology, Diagnosis and Treatment)

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13 pages, 1615 KiB

Open AccessArticle

Prognostic and Pathophysiologic Significance of IL-8 (CXCL8) in Biliary Atresia

by Nimish Godbole, Iiris Nyholm, Maria Hukkinen, Joseph R. Davidson, Athanasios Tyraskis, Katja Eloranta, Noora Andersson, Jouko Lohi, Päivi Heikkilä, Antti Kyrönlahti, Marjut Pihlajoki, Mark Davenport, Markku Heikinheimo and Mikko P. Pakarinen

J. Clin. Med. 2021, 10(12), 2705; https://doi.org/10.3390/jcm10122705 - 18 Jun 2021

Cited by 11 | Viewed by 1657

Abstract

Interleukin (IL)-8 (CXCL8), a chemokine involved in neutrophil recruitment, has been implicated in ductular reaction and liver fibrogenesis. We studied liver and serum IL-8 expression in a large biliary atresia (BA) cohort and explored its prognostic and pathophysiological potential. IL-8 expression was assessed [...] Read more.

Interleukin (IL)-8 (CXCL8), a chemokine involved in neutrophil recruitment, has been implicated in ductular reaction and liver fibrogenesis. We studied liver and serum IL-8 expression in a large biliary atresia (BA) cohort and explored its prognostic and pathophysiological potential. IL-8 expression was assessed in liver utilizing quantitative polymerase chain reaction (qPCR), immunohistochemistry and in situ hybridization and in serum using an enzyme-linked immunosorbent assay, among 115 BA patients, 10 disease controls and 68 normal controls. Results were correlated to portoenterostomy (PE) outcomes, biochemical and histological liver injury, transcriptional markers of fibrosis and cholangiocytes, and expression of other related cytokines. IL-8 was markedly overexpressed in liver and serum of BA patients at PE (n = 88) and in serum samples obtained during postoperative follow-up (n = 40). IL-8 expression in the liver was predominantly in cholangiocytes within areas of ductular reaction. Liver IL-8 mRNA expression correlated positively with its serum concentration, bile ductular proliferation, Metavir fibrosis stage, and transcriptional markers of activated myofibroblasts (ACTA2) and cholangiocytes (KRT19). Taken together, IL-8 may mediate liver injury in BA by promoting ductular reaction and associated liver fibrogenesis. Prognostic value of serum IL-8 to predict native liver survival was limited and confined to the postoperative period after PE. Full article

(This article belongs to the Special Issue Biliary Atresia: Aetiology, Diagnosis and Treatment)

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Review

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14 pages, 901 KiB

Open AccessReview

Biliary Atresia in Adolescence and Adult Life: Medical, Surgical and Psychological Aspects

by Deirdre Kelly, Marianne Samyn and Kathleen B. Schwarz

J. Clin. Med. 2023, 12(4), 1594; https://doi.org/10.3390/jcm12041594 - 17 Feb 2023

Cited by 2 | Viewed by 1930

Abstract

Prior to 1955, when Morio Kasai first performed the hepatic portoenterostomy procedure which now bears his name, Biliary atresia (BA) was a uniformly fatal disease. Both the Kasai procedure and liver transplantation have markedly improved the outlook for infants with this condition. Although [...] Read more.

Prior to 1955, when Morio Kasai first performed the hepatic portoenterostomy procedure which now bears his name, Biliary atresia (BA) was a uniformly fatal disease. Both the Kasai procedure and liver transplantation have markedly improved the outlook for infants with this condition. Although long-term survival with native liver occurs in the minority, survival rates post liver transplantation are high. Most young people born with BA will now survive into adulthood but their ongoing requirements for health care will necessitate their transition from a family-centred paediatric service to a patient-centred adult service. Despite a rapid growth in transition services over recent years and progress in transitional care, transition from paediatric to adult services is still a risk for poor clinical and psychosocial outcomes and increased health care costs. Adult hepatologists should be aware of the clinical management and complications of biliary atresia and the long-term consequences of liver transplantation in childhood. Survivors of childhood illness require a different approach to that for young adults presenting after 18 years of age with careful consideration of their emotional, social, and sexual health. They need to understand the risks of non-adherence, both for clinic appointments and medication, as well as the implications for graft loss. Developing adequate transitional care for these young people is based on effective collaboration at the paediatric–adult interface and is a major challenge for paediatric and adult providers alike in the 21st century. This entails education for patients and adult physicians in order to familiarise them with the long-term complications, in particular for those surviving with their native liver and the timing of consideration of liver transplantation if required. This article focusses on the outcome for children with biliary atresia who survive into adolescence and adult life with considerations on their current management and prognosis. Full article

(This article belongs to the Special Issue Biliary Atresia: Aetiology, Diagnosis and Treatment)

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Open AccessReview

Biliary Atresia: Clinical Phenotypes and Aetiological Heterogeneity

by Mark Davenport, Ancuta Muntean and Nedim Hadzic

J. Clin. Med. 2021, 10(23), 5675; https://doi.org/10.3390/jcm10235675 - 01 Dec 2021

Cited by 21 | Viewed by 5406

Abstract

Biliary atresia (BA) is an obliterative condition of the biliary tract that presents with persistent jaundice and pale stools typically in the first few weeks of life. While this phenotypic signature may be broadly similar by the time of presentation, it is likely [...] Read more.

Biliary atresia (BA) is an obliterative condition of the biliary tract that presents with persistent jaundice and pale stools typically in the first few weeks of life. While this phenotypic signature may be broadly similar by the time of presentation, it is likely that this is only the final common pathway with a number of possible preceding causative factors and disparate pathogenic mechanisms—i.e., aetiological heterogeneity. Certainly, there are distinguishable variants which suggest a higher degree of aetiological homogeneity such as the syndromic variants of biliary atresia splenic malformation or cat-eye syndrome, which implicate an early developmental mechanism. In others, the presence of synchronous viral infection also make this plausible as an aetiological agent though it is likely that disease onset is from the perinatal period. In the majority of cases, currently termed isolated BA, there are still too few clues as to aetiology or indeed pathogenesis. Full article

(This article belongs to the Special Issue Biliary Atresia: Aetiology, Diagnosis and Treatment)

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8 pages, 613 KiB

Open AccessBrief Report

Prepregnancy Assessment of Liver Function to Predict Perinatal and Postpregnancy Outcomes in Biliary Atresia Patients with Native Liver

by Nobuhiro Takahashi, Daigo Ochiai, Yohei Yamada, Masumi Tamagawa, Hiroki Kanamori, Mototoshi Kato, Satoru Ikenoue, Yoshifumi Kasuga, Tatsuo Kuroda and Mamoru Tanaka

J. Clin. Med. 2021, 10(17), 3956; https://doi.org/10.3390/jcm10173956 - 31 Aug 2021

Cited by 2 | Viewed by 2059

Abstract

Considering that some biliary atresia (BA) survivors with native liver have reached reproductive age and face long-lasting complications, specific attention needs to be paid to pregnant cases. This study aimed to investigate the relationship between liver function, perinatal outcomes, and prognosis. A database [...] Read more.

Considering that some biliary atresia (BA) survivors with native liver have reached reproductive age and face long-lasting complications, specific attention needs to be paid to pregnant cases. This study aimed to investigate the relationship between liver function, perinatal outcomes, and prognosis. A database review was conducted to identify pregnant BA cases with native liver and perinatal data, and clinical information on BA-related complications was analyzed. Perinatal serum cholinesterase (ChE) levels, model for end-stage liver-disease (MELD) score, and platelet trends were analyzed, and the association between these indicators and perinatal outcomes was investigated. Patients were categorized into three groups according to the perinatal clinical outcomes: favorable (term babies with or without several episodes of cholangitis; n = 3), borderline (term baby and following liver dysfunction; n = 1), and unfavorable (premature delivery with subsequent liver failure; n = 1). Lower serum ChE levels, lower platelet counts, and higher MELD scores were observed in the unfavorable category. Borderline and unfavorable patients displayed a continuous increase in MELD score, with one eventually needing a liver transplantation. Pregnancy in patients with BA requires special attention. Serum ChE levels, platelet counts, and MELD scores are all important markers for predicting perinatal prognosis. Full article

(This article belongs to the Special Issue Biliary Atresia: Aetiology, Diagnosis and Treatment)

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