RARE DISEASE
Syndromic biliary atresia
Syndromic biliary atresia
Syndromic biliary atresia
Drug discovery
0
drugs
With orphan designations
Overview
Syndromic biliary atresia is a congenital obstructive cholangiopathy characterized by extrahepatic bile duct obliteration alongside visceral, vascular, or cardiac anomalies, most notably in biliary atresia splenic malformation (BASM) syndrome. Associated features include polysplenia, situs inversus, preduodenal portal vein, and cardiac defects, reflecting embryonic developmental disruption. Management requires early surgical intervention, though prognosis remains guarded due to progressive liver fibrosis and high transplant dependency [1][4][15].
Burden
Leading cause of pediatric liver transplantation globally; 10-year transplant-free survival is <25% despite KPE [4][6][15].
High morbidity: Recurrent cholangitis (20–78%), portal hypertension, and growth failure [2][5][6].
Mortality driven by cirrhosis, sepsis, or comorbidities (e.g., cardiac anomalies) [1][2][16].
Therapies
Kasai portoenterostomy (KPE): Primary surgical intervention, with timing critical (<60–90 days old) [3][6][13].
Liver transplantation: Required in ~50% of cases by adolescence due to cirrhosis or failed KPE [3][4][6].
Adjunctive therapies: Postoperative antibiotics (e.g., trimethoprim-sulfamethoxazole), ursodiol, and nutritional optimization (MCT oil, fat-soluble vitamins) [3][5][11].
Categories: rare hepatic diseases
Research Papers
392 drug discovery papers about Syndromic biliary atresia, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
392 drug discovery papers about Syndromic biliary atresia, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-14 | Real-world use of maralixibat in biliary atresia: a case series
Biliary atresia (BA) is the most common cause of cholestasis in infants, and pruritus may be a prominent and debilitating complication. Maralixibat is the first US Food and Drug Administration–approved drug for the treatment of cholestatic pruritus in children with Alagille syndrome and has been subsequently approved for treatment of progressive familial intrahepatic cholestasis as well. Several patients with BA have received maralixibat as part of a compassionate use program. We report the use of maralixibat for the treatment of cholestatic pruritus in BA for six patients. Demographics, past medical history, laboratory markers, and medications were collected. Pruritus was assessed using the Clinician Scratch Scale (CSS) at baseline and last clinical follow-up. All patients reported improved CSS with no increased usage of other antipruritic medications, and the medication was well tolerated.
2026-05-01 | C62-24 Follicular Bronchiolitis Following Liver Transplant in a Young Child
Abstract Introduction Inflammatory bronchiolitis following non-lung solid organ transplant (SOT) is rare but has been described in case reports. Herein, we present a child with clinical and radiologic evidence of small airways disease and biopsy evidence of follicular bronchiolitis following liver transplant. Case Report A six-year-old girl was referred for intermittent increased work of breathing, cough and exertional dyspnea 3 months following cadaveric liver transplant for failed Kasai for biliary atresia. Chest CT demonstrated diffuse bilateral mosaicism and bronchial wall thickening consistent with airways inflammation and gas trapping (Figure 1A). Spirometry attempts were unsuccessful, but multiple breath nitrogen washout demonstrated an elevated lung clearance index (LCI) at 10.8 (normal <7.1). Flexible bronchoscopy was macroscopically unremarkable. Bronchoalveolar lavage fluid analysis demonstrated neutrophilic alveolitis on cell count (80% neutrophils) and cytopathology. Extensive microbiological testing failed to identify evidence of bacterial, viral or fungal pathogens. Surgical lung biopsy demonstrated follicular bronchiolitis with mixed population lymphocytic infiltrates of the small airways and no evidence of fibrosis or luminal obliteration (Figure 1B-D). Chimerism analysis performed on donor and recipient peripheral blood, and lung tissue, failed to reveal donor derived cells. She commenced treatment with monthly pulse methylprednisolone (30 mg/kg/day for 3 days) for 3 months, daily oral prednisone (1 mg/kg/day), thrice weekly azithromycin and twice daily inhaled fluticasone/salmeterol. She demonstrated clinical improvement following the second corticosteroid pulse, coinciding with normalization of LCI to 6.6. Her symptoms completely resolved by 3 months following the final methylprednisolone pulse. Prednisone was weaned and ceased 6 months following the final pulse of methylprednisolone. She remained clinically well with a normal LCI at 3 months following complete cessation of corticosteroids. Azithromycin was ceased with a plan for future cessation of fluticasone/salmeterol. Novelty & Importance Our patient presented 3 months after SOT with clinical and radiographic changes consistent with small airways disease, and a pathological diagnosis of follicular bronchiolitis (FB). FB is a pathological diagnosis characterized by proliferation of bronchus-associated lymphoid tissue with resultant peribronchial follicles. It is associated with multiple etiologies, including infection, autoimmune disease and immunodeficiency. However, it has also been described in lung transplant recipients presenting with bronchiolitis obliterans syndrome (BOS). To our knowledge, this is the first description of FB following pediatric non-lung SOT. Despite extensive testing, including molecular chimerism testing, no clear cause of FB was identified. She responded well to standard BOS treatment with corticosteroids, azithromycin and fluticasone/salmeterol. This case supports investigation and treatment for BOS in this setting. This abstract is funded by: None
2025-05-20 | Vitamin K deficiency bleeding and optimal prophylaxis methods in biliary atresia: A surveillance study in Japan.
Vitamin K (VK) prophylaxis refers to the administration of VK to newborns to prevent neonatal VK deficiency bleeding (VKDB), which is characterized by intracranial hemorrhage (ICH). This study investigated the relationship between VK prophylaxis methods and VKDB in biliary atresia (BA). The survey targeted 497 cases in the Japanese Biliary Atresia Registry between 2015 and 2019, of which 395 (79.5%) returned the questionnaire. Of the 395 patients, 289 were selected after excluding cases in which the gestational age was <36 weeks or the VK prophylaxis methods/feeding contents were unknown. The patients were categorized into two groups according to VK prophylaxis methods. We conducted a comparative study using propensity score matching. The prognosis of patients with or without ICH was also investigated. In the analysis, no VKDB occurred in patients using the 3-month method. In the propensity score matching analysis, age at first visit and age at surgery were later in the three-times method (p = 0.018 and p = 0.022, respectively); VKDB was higher in the three-times method than in the 3-month method (p = 0.029). ICH, jaundice disappearance, cholangitis, and native liver survival rates (NLSRs) were not significantly different between groups. When examining the prognosis based on ICH occurrence, the two groups showed no significant differences in jaundice disappearance, cholangitis, and NLSRs. The ICH group had a greater number of cases of delayed mental and/or motor development. In BA, the 3-month method is effective in preventing VKDB, and early diagnosis is crucial.
2025-03-30 | Passenger Lymphocyte Syndrome with Hepatic Sinusoidal Obstruction Syndrome in an Infant Following Living Donor Liver Transplantation: An Association or Coincidence?
A 7-month-old male infant with AB blood type, diagnosed with biliary atresia and uncompensated cirrhosis postKasai procedure, underwent living donor liver transplantation with a 260-g left lateral segment graft from a blood type B donor. Intraoperatively, the patient received a transfusion of type AB red blood cells. Immunosuppressive therapy included tacrolimus and prednisone. The recovery period was uneventful until postoperative day 18, when the patient developed a fever, changed mental status, and impaired liver functions. Further tests revealed an increased bilirubin level, decreased hemoglobin and platelet counts, detectable anti-A antibodies, and a positive direct Coombs test. A considerable increase in B lymphocytes indicated a diagnosis of passenger lymphocyte syndrome (PLS), which was managed with adjustments to immunosuppression, intravenous immunoglobulin infusion, type B red blood cell transfusion, and supportive care. Interestingly, 1 month after the diagnosis of PLS, a routine computed tomography angiography showed an enlarged liver with patchy enhancement and obscured hepatic veins. Based on the presence of ascites, the clinical diagnosis of hepatic sinusoidal obstruction syndrome (HSOS) was established. Management included transitioning from tacrolimus to cyclosporine and administering low-molecular-weight heparin injections. The condition of the patient improved over 3 weeks, and subsequently, the patient was discharged. To conclude, this report raises the question of a potential correlation between PLS and HSOS in this patient. While PLS is not presently recognized as an established cause of HSOS, the lymphocyte proliferation and antibody production found in PLS can potentially damage the hepatic sinusoidal endothelial cells.
2025-01-22 | Recent advances in the management of pediatric cholestatic liver diseases.
Pediatric cholestatic liver diseases are rare conditions that can result from multiple specific underlying etiologies. Among the most common etiologies of pediatric cholestatic liver diseases are biliary atresia, Alagille syndrome (ALGS), and inherited disorders of bile acid transport. These diseases are characterized by episodic or chronic unremitting cholestasis. Due to the chronicity of these conditions, it is imperative to optimize medical management to improve patient quality of life, provide nutritional support, and reduce bile acid toxicity in efforts to slow disease progression. Cholestatic liver diseases remain the leading cause of pediatric liver transplantation, as many underlying disease etiologies have no curative medical therapies. In the present review, we provide an update on the nutritional, medical, and surgical management of pediatric cholestatic liver diseases. As recent advances have occurred in the field with the addition of ileal bile acid transporter (IBAT) inhibitors, we also review the results from prospective clinical trials, including their strengths and limitations. While recent clinical trials have demonstrated improved pruritus using IBAT inhibitors in ALGS and progressive familial intrahepatic cholestasis, establishing medical therapies proven to slow disease progression remains an area of unmet need.
cell therapies
2025-03-28 | Liver transplantation in children: pre-transplantation preparation tactics
Liver transplantation (LT) from a living related donor is the only life-saving option for children with congenital liver diseases such as biliary atresia, Alagille syndrome, progressive familial intrahepatic cholestasis, and Byler disease, as well as metabolic disorders and acute or chronic liver failure. The development of LT from living related donors significantly reduces the waiting time for a donor organ. The success of the procedure largely depends on the quality of pre-transplantation preparation (PTP) of both donor and recipient. Aim - to study the features of PTP in children with cholestatic liver diseases for successful LT. Materials and methods. 37 children with biliary atresia underwent PTP between 2005 and 2023. In 36 cases, LT was performed using a living related donor; in one case, split-liver transplantation (SPLIT-LT) was used. PTP lasted 3–6 months and included infection focus sanitation, correction of congenital anomalies, emergency status assessment, and evaluation of physical and psycho-emotional development. All examinations followed current international standards. Results. All transplantations were successful. After PTP, improvements were observed in hematological parameters, functional and neuropsychological development, and reduced anxiety levels. All transplant centers acknowledged the high quality of PTP; no child was refused transplantation due to inadequate preparation. The key readiness criteria were a compensated clinical state and a safe bacterial environment. Conclusions. Compliance with regulatory standards and protocols for PTP ensures successful pediatric LT and protects donor health. PTP improves hematological, somatic, and psycho-emotional indicators, reduces risks, and increases the effectiveness of transplantation. Our experience with PTP aligns with international standards. The research was carried out in accordance with the principles of the Declaration of Helsinki. Informed consent of the child and child's parents was obtained for the research. No conflict of interest was declared by the author.
2024-09-01 | P.484: Liver transplant in a patient with syndromatic bile atresia without polysplenia case report.
Introduction: Biliary atresia (BA) is obliterative cholangiopathy with an incidence of 1: 10,000-15,000 live births. Syndromic BA is associated with other congenital anomalies, such as interruption of the inferior cava vein, preduodenal portal vein, abnormal intestinal rotation, complete visceral transposition, cardiac anomalies and polysplenia, this occurs in 10% of patients, it´s believed that there is a relationship between BA and maternal diabetes. Objective: to present the experience of a patient with syndromatic bile duct atresia and a related living donor liver transplant (LDLT). Clinical report: Female, with maternal history of type II diabetes, 1 year 6 months old, started suffering from Cholestatic jaudince at 15 days of life, after the work-up for jaundice, the diagnosis of type III BA was made, plus another clinical features malrotation, pre-duodenal portal vein, cardiac anomalie Intraventricular septal defect: mean muscular intraventricular communication of 1.7 mm, shunt from left to right with a gradient of 60 mm without hemodynamic repercussion, patent foramen ovale of 2 mm and dyslipidemia. Despite the kasai, he did not have bile clearance, with little growth with a weight of 7.5 kg an addition to worsening liver failure with a CHILD – PUGH B with 7 pounts and PELD 24 pounts, so it was decided to perform an LDLT. During the surgical event, the following findings were reported: annular pancreas with preduodenal portal vein, single kidney-shaped spleen without polysplenia, agenesis of the retrohepatic cava, agenesis of the celiac trunk, left hepatic artery coming from the left gastric artery, direct gastric artery from the aorta, right hepatic artery coming from the superior mesenteric artery and incomplete intestinal malrotation. The transplant was performed successfully, as well as a prophylactic appendectomy and placement of a biodegradable biliary stent in the roux. In his post-surgical evolution, he presented partial thrombosis of the portal vein in hepatic segment II, which resolved favorably with anticoagulation in the first 2 days. after LT (LT). Conclusion: The anatomical variants of a syndromatic atresia require great knowledge and vascular control so as not to lose the only possibility of arterial and portal anastomosis that the patient has, in this case the total release of the portal vein without injuring the pancreas or the duodenum represented a challenge. We present our successful experience in the complex surgical approach to a liver transplant with syndromatic atresia. Dra Nidia de Monserrat Arreola.
2023-12-15 | Living donor liver transplantation: 35 years of saving lives
The first liver transplantation was performed by Thomas E Starzl in a child with biliary atresia in 1963.1Starzl TE Marchioro TL Vonkaulla KN Hermann G Brittain RS Waddell WR Homotransplantation of the liver in humans.Surg Gynecol Obstet. 1963; 117: 659-676PubMed Google Scholar Despite initial setbacks, longer survival rates followed. The disproportion of donor graft size to recipient size initially posed a problem in paediatric liver transplantation. Several techniques were described to mitigate the issue: first, graft reduction by Bismuth and Houssin in 1984,2Bismuth H Houssin D Reduced-sized orthotopic liver graft in hepatic transplantation in children.Surgery. 1984; 95: 367-370PubMed Google Scholar and then split liver transplantation by Pichlmayr and colleagues in 1988.3Pichlmayr R Ringe B Gubernatis G Hauss J Bunzendahl H Transplantation of a donor liver to 2 recipients (splitting transplantation)—a new method in the further development of segmental liver transplantation.Langenbecks Arch Chir. 1988; 373: 127-130Crossref PubMed Scopus (489) Google Scholar In 1989, Raia and colleagues4Raia S Nery JR Mies S Liver transplantation from live donors.Lancet. 1989; 2: 497Abstract PubMed Scopus (609) Google Scholar described the first two living donor liver transplantations for paediatric recipients. The technique was followed by an ethical dilemma,5McMaster P Live donors and hepatic transplantation.Lancet. 1989; 2: 1042-1043Abstract PubMed Scopus (3) Google Scholar with concerns for donor safety in a more technically challenging surgery compared with living donor kidney transplantation, which was an accepted procedure at the time. Despite these initial concerns, living donor liver transplantations gained momentum, especially in regions where cultural and religious barriers did not allow the use of deceased donor organs. The procedure expanded from paediatric to adult recipients, and from selected recipients to patients with high urgency criteria, thanks to technical advances. These advances included the use of left lobe grafts, right lobe grafts, modified right lobe grafts, and dual grafts in adults to overcome small-for-size syndrome. Other advancements also supported the growth of living donor liver transplantations, including techniques for graft reduction in paediatric liver transplantation, such as hyper-reduction and anterior hepatic resection of the left lateral segment, and the use of true monosegments to avoid large-for-size syndrome. The success of the procedure must be attributed, in part, to the attention given to the surgery and the postoperative care of the donors, as the wellbeing of these altruistic individuals is essential to any living donor programme. A substantial concern is organ trafficking, and the medical community must remain continuously vigilant to combat these activities to maintain public trust in this procedure. 35 years after it was first described, living donor liver transplantation has evolved into an established surgical procedure, and continues to break new ground, with innovations ranging from open donor hepatectomies to laparoscopic and robotic liver resections. The technique has proven to be safe and has saved more than 80 000 lives worldwide since 2000, according to the Global Observatory on Donation and Transplantation. Going forward, exercising continuous vigilance regarding donor health will be essential to ensure continuity and future advancements in living donor liver transplantations. We declare no competing interests.
2021-01-07 | Liver-only Transplantation in a Patient With Complex Congenital Heart Disease: Case Report and Review of the Literature
Patients with liver failure due to or in addition to congenital heart disease (CHD) represent a growing population in need of organ transplantation. Traditionally, these patients received a combined heart and liver transplantation carrying a high risk of perioperative morbidity and mortality.We discuss a patient with complex cyanotic CHD and biliary atresia undergoing liver-only transplantation. Furthermore, a literature study was performed on combined congenital heart and liver disease in the setting of transplantation.We describe a unique case of a patient with severe CHD undergoing orthotopic liver transplantation for biliary atresia. In the literature, congenital malformations affecting different organs seems not that infrequent. Liver-only transplantation has been described in mild CHD, although data in adult patients are scarce. In severe CHD, the liver usually suffers from congestion. The severity of liver disease and reversibility should be estimated to decide on combined heart-liver transplantation.Our case and a review of the literature demonstrate that a patient-tailored approach with liver-only transplantation may be an appropriate alternative to combined heart and liver transplantation in selected cases.
2019-09-18 | Outcomes of paediatric liver transplant for biliary atresia
Despite the widespread use of Kasai Portoenterostomy (KPE) for biliary atresia, more than two thirds of these patients require liver transplant. Liver transplantation is not widely available in South Africa, and Wits Donald Gordon Medical Centre is one of two centres performing paediatric liver transplantation in the country, and the only centre performing living related donor transplants.A retrospective review was performed at the centre. Demographic data were collected, and tabulated. Survival analysis was performed using the Kaplan Meier method. Complication rates were categorised into biliary, vascular and enteric, and classified as early and late.Sixty-seven first time liver transplants were performed for biliary atresia at WDGMC from 2005 to 2017. Sixty-nine percent were female patients and thirty-one percent were male patients. Forty-eight percent of patients under the age of 5 years had a z-score of -2 or worse for mid upper arm circumference (MUAC). One year overall survival of the cohort is 84.5%, and overall graft survival is 82.9%. Overall mortality was 22%, with infection being the most common cause of death.Early referral of all patients with biliary atresia to a paediatric liver transplant centre is essential for early assessment of indications, and medical and nutritional optimisation of patients. Primary liver transplant should be considered for a select group of patients with unique clinical indications.
antibodies
2024-05-01 | ABO Incompatible Living Donor Liver Transplantation in Children: A Single Centre Experience from India
Background In recent years, paediatric ABO incompatible (ABOi) living donor liver transplant (LT) has shown promising outcomes and can potentially eliminate organ shortage. This study aims to report paediatric ABOi LT experience, including short- and long-term outcomes. Methods It is a single-centre retrospective study. Out of 108 LTs, 20 were done in children. We compared the outcomes between ABOi (n = 20) and non-ABOi (n = 220) paediatric living donor liver transplantation (LDLT) performed during the study period. All the children received pre-LT desensitization therapy comprising rituximab and plasmapheresis targeting pre-LT isohemagglutinin (IHA) titres of ≤1:16. Results Out of 239 paediatric LDLTs from 2017 to 2022, 19 children (11 females) underwent 20 ABOi LTs (including one retransplant with an ABOi domino allograft) at a median age of 12 (12, 51) months, with the majority being biliary atresia (60%). The median change in CD19 cell%, CD20 cell%, and IHA titres after rituximab from day −14 to day −1 (before LT) was satisfactory. In the first 3 months following LT, acute cellular rejection, culture-proven sepsis, and biliary and vascular complications were seen in 10%, 20%, 20%, and 15%, respectively. None of the ABOi LT recipients developed antibody-mediated rejection. ABOi LT recipients, as compared to non-ABOi LT recipients, had a higher incidence of bile leaks and prolonged hospital stay, with the rest of the complications, including biliary strictures and long-term outcomes, being comparable. At a median follow-up of 21 (14, 33) months, 4 children expired (21%). Conclusion ABOi LT in children shows excellent outcomes and can be performed safely with prior desensitization when a compatible liver is unavailable. In recent years, paediatric ABO incompatible (ABOi) living donor liver transplant (LT) has shown promising outcomes and can potentially eliminate organ shortage. This study aims to report paediatric ABOi LT experience, including short- and long-term outcomes. It is a single-centre retrospective study. Out of 108 LTs, 20 were done in children. We compared the outcomes between ABOi (n = 20) and non-ABOi (n = 220) paediatric living donor liver transplantation (LDLT) performed during the study period. All the children received pre-LT desensitization therapy comprising rituximab and plasmapheresis targeting pre-LT isohemagglutinin (IHA) titres of ≤1:16. Out of 239 paediatric LDLTs from 2017 to 2022, 19 children (11 females) underwent 20 ABOi LTs (including one retransplant with an ABOi domino allograft) at a median age of 12 (12, 51) months, with the majority being biliary atresia (60%). The median change in CD19 cell%, CD20 cell%, and IHA titres after rituximab from day −14 to day −1 (before LT) was satisfactory. In the first 3 months following LT, acute cellular rejection, culture-proven sepsis, and biliary and vascular complications were seen in 10%, 20%, 20%, and 15%, respectively. None of the ABOi LT recipients developed antibody-mediated rejection. ABOi LT recipients, as compared to non-ABOi LT recipients, had a higher incidence of bile leaks and prolonged hospital stay, with the rest of the complications, including biliary strictures and long-term outcomes, being comparable. At a median follow-up of 21 (14, 33) months, 4 children expired (21%). ABOi LT in children shows excellent outcomes and can be performed safely with prior desensitization when a compatible liver is unavailable.
2022-02-02 | Transplant-associated thrombotic microangiopathy and acquired nephrotic syndrome: A case report in a 35-month child.
Abstract Background Transplant-associated thrombotic microangiopathy (TA-TMA) presents with thrombocytopenia, nonimmune hemolytic anemia, peripheral blood schistocytes and end-organ damage to the kidney. TA-TMA is associated with a significant increased morbidity and mortality, especially when treatment is not initiated early. We present a pediatric clinical case of a 35-month child with history of hepatic transplantation, who develop the clinical spectrum of TA-TMA and acquired nephrotic syndrome. Case presentation: A 35-month-old boy with history of hepatic transplantation secondary of atresia of biliary ducts who received immunosuppressive therapy with tacrolimus, mycophenolate and steroids. He presents with 4 days of fever, vomiting, and non-dysenteric diarrhea. He received an initial course of antibiotics without response. After 3 days he continues with fever, low urine output and edema. Vital signs showed high blood pressure and physical exam revealed facial and extremity edema. Laboratory results showed proteinuria and hematuria, low albumin, and high triglycerides. All possible etiologies of nephrotic syndrome were ruled out. Kidney biopsy showed TMA changes. Plasma exchange and Eculizumab were started with clinical improvement. Discussion TMA can be classified as a primary or secondary. Primary TMA can be hereditary or acquired. Acquired TMA included the ones triggered by medications. This clinical syndrome has been described as an endothelial dysfunction secondary of an immune reaction over the endothelium and/or a direct cytotoxic effect over endothelium and platelets. In this case report the use of calcineurin inhibitors (tacrolimus) one of the most common drugs associated with TMA was one the triggers factors. Recent publications have described how these patients that are exposed to any triggers has also a genetically predisposing to develop TMA. There is a lack in diagnostics and prognostic markers. The earliest treatment is stared, the better prognosis and outcomes.
2019-05-01 | 2. Answering the Donor Graft Shortage - Successful Outcome of ABO Incompatible Pediatric Living Related Liver Transplants
Background and Aims: ABO-incompatible (ABOi) liver transplantation is usually contraindicated because of risk of antibody-mediated humoral rejection of graft. Ours is a busy living related liver transplant (LDLT) center. We describe 8 successful cases of patients who had LDLT from ABOi donors. Methods: Study period-July 2010 to April 2018. ABOi LDLT patients <18 years age. Protocol consisted of rituximab 2 weeks prior (>3 years) and plasmapheresisbefore LDLT. Target anti ABOtitres pre-transplant was less than 1:16. Plasmapheresis to aim anti-ABO titers below 1:32 was planned up to 4 weeks post-op. Mycophenolate was started one week prior to transplant. No child was splenectomized and no local graft infusion used. Standard triple immune suppression (Steroid, Mycophenolate Mofetil and Tacrolimus) was used post operatively. Results: Out of 200 Pediatric LDLT patients, 8 were ABO incompatible (ABOi). Indications- Biliary Atresia- 4; PFIC – 2, Chronic rejection 1 (re-transplant), Alagille syndrome. Median age 31 months (7–91); median PELD score 24 (19–42). Mean graft-to-recipient weight ratio 2.1. Initial range of isoagglutinin IgM and IgG titers were 1:32–1:256 and 1:64–1:256 respectively in 6 patients on whom 2–4 cycles of cascade plasmapheresis done preoperatively. One patient had titre 1:1024 where immune adsorption technique was used in view of 3 failed plasmapheresis along with Rituximab. Another 1 patient underwent urgent transplant in whom Immunoadsorption technique was used. Postoperative IVIG was used in 2 patients. Postoperative complications included portal vein thrombosis (one-successfully re-explored), bacterial infection (one), fungal infection (one) and CMV infection (one) based on culture reports. Mean hospital stay was 26 days (15–59 range). Patient and graft survival was 100% in recipients at a mean follow-up of 33 months (range 2–80 months). Conclusions: ABO-incompatible LDLT can be safely performed in children with excellent outcome. Preoperative reduction of antibody titres<1:32 by plasmapheresis is essential for successful LT. Immuno-adsorption (glycosorb) technique is more effective than routine cascade plasmapheresis in patients with very high antibody titres. The authors have none to declare.
2018-07-01 | 10. Successful outcome of ABO incompatible pediatric living related liver transplant using the standard immunosuppression
Background and Aims: ABO-incompatible (ABOi) liver transplantation is usually contraindicated because of risk of antibody-mediated humoral rejection of graft. Ours is a busy living related liver transplant (LDLT) center. We describe 6 successful cases of patients who had LDLT from ABOi donors. Methods: Study period-July 2010 to April 2018. ABOi LDLT patients <18 years age. Protocol consisted of rituximab 2 weeks prior (>3 years) and plasmapheresis before LDLT. Target anti ABO titres pre-transplant was less than 1:16. Plasmapheresis to aim anti-ABO titers below 1:32 was planned upto 4 weeks post-op. Mycophenolate was started one week prior to transplant. No child was splenectomized and no local graft infusion used. Standard triple immune suppression (Steroid, Mycophenolate Mofetil and Tacrolimus) was used post operatively. Results: Out of 200 Pediatric LDLT patients, 7 were ABO incompatible (ABOi). Indications- Biliary Atresia- 4; PFIC – 2, Chronic rejection 1 (re-transplant). Median age 33 months (7–91); median PELD score 24 (19–42). Mean graft-to-recipient weight ratio 1.79. Initial range of isoagglutinin IgM and IgG titers were 1:32–1:256 and 1:64–1:256 respectively in 6 patients on whom median 4 (range 2–6) cycles of plasmapheresis done. One patient had titre 1:1024 where immune adsorption technique was used in view of 3 failed plasmapheresis along with Rituximab. Postoperative IVIG was used in 2 patients. No rejection, bacterial or fungal infections noted. Postoperative complications included portal vein thrombosis (one-successfully re-explored) and CMV infection (one). Mean hospital stay was 19 days (18–23 range). Patient and graft survival was 100% in recipients at a mean follow-up of 24 months (range 1–59 months). Conclusions: ABO-incompatible LDLT can be safely performed in children. Preoperative reduction of antibody titres <1:32 by plasmapheresis is essential for successful LT. Immuno-adsorption (glycosorb) technique is more effective than routine cascade plasmapheresis in patients with very high antibody titres. The authors have none to declare.
2017-11-22 | Large-scale proteomics identifies MMP-7 as a sentinel of epithelial injury and of biliary atresia
Biliary atresia is a progressive infantile cholangiopathy of complex pathogenesis. Although early diagnosis and surgery are the best predictors of treatment response, current diagnostic approaches are imprecise and time-consuming. We used large-scale, quantitative serum proteomics at the time of diagnosis of biliary atresia and other cholestatic syndromes (serving as disease controls) to identify biomarkers of disease. In a discovery cohort of 70 subjects, the lead biomarker was matrix metalloproteinase-7 (MMP-7), which retained high distinguishing features for biliary atresia in two validation cohorts. Notably, the diagnostic performance reached 95% when MMP-7 was combined with γ-glutamyltranspeptidase (GGT), a marker of cholestasis. Using human tissue and an experimental model of biliary atresia, we found that MMP-7 is primarily expressed by cholangiocytes, released upon epithelial injury, and promotes the experimental disease phenotype. Thus, we propose that serum MMP-7 (alone or in combination with GGT) is a diagnostic biomarker for biliary atresia and may serve as a therapeutic target.
small molecules
2026-08-14 | Real-world use of maralixibat in biliary atresia: a case series
Biliary atresia (BA) is the most common cause of cholestasis in infants, and pruritus may be a prominent and debilitating complication. Maralixibat is the first US Food and Drug Administration–approved drug for the treatment of cholestatic pruritus in children with Alagille syndrome and has been subsequently approved for treatment of progressive familial intrahepatic cholestasis as well. Several patients with BA have received maralixibat as part of a compassionate use program. We report the use of maralixibat for the treatment of cholestatic pruritus in BA for six patients. Demographics, past medical history, laboratory markers, and medications were collected. Pruritus was assessed using the Clinician Scratch Scale (CSS) at baseline and last clinical follow-up. All patients reported improved CSS with no increased usage of other antipruritic medications, and the medication was well tolerated.
2026-05-01 | C62-24 Follicular Bronchiolitis Following Liver Transplant in a Young Child
Abstract Introduction Inflammatory bronchiolitis following non-lung solid organ transplant (SOT) is rare but has been described in case reports. Herein, we present a child with clinical and radiologic evidence of small airways disease and biopsy evidence of follicular bronchiolitis following liver transplant. Case Report A six-year-old girl was referred for intermittent increased work of breathing, cough and exertional dyspnea 3 months following cadaveric liver transplant for failed Kasai for biliary atresia. Chest CT demonstrated diffuse bilateral mosaicism and bronchial wall thickening consistent with airways inflammation and gas trapping (Figure 1A). Spirometry attempts were unsuccessful, but multiple breath nitrogen washout demonstrated an elevated lung clearance index (LCI) at 10.8 (normal <7.1). Flexible bronchoscopy was macroscopically unremarkable. Bronchoalveolar lavage fluid analysis demonstrated neutrophilic alveolitis on cell count (80% neutrophils) and cytopathology. Extensive microbiological testing failed to identify evidence of bacterial, viral or fungal pathogens. Surgical lung biopsy demonstrated follicular bronchiolitis with mixed population lymphocytic infiltrates of the small airways and no evidence of fibrosis or luminal obliteration (Figure 1B-D). Chimerism analysis performed on donor and recipient peripheral blood, and lung tissue, failed to reveal donor derived cells. She commenced treatment with monthly pulse methylprednisolone (30 mg/kg/day for 3 days) for 3 months, daily oral prednisone (1 mg/kg/day), thrice weekly azithromycin and twice daily inhaled fluticasone/salmeterol. She demonstrated clinical improvement following the second corticosteroid pulse, coinciding with normalization of LCI to 6.6. Her symptoms completely resolved by 3 months following the final methylprednisolone pulse. Prednisone was weaned and ceased 6 months following the final pulse of methylprednisolone. She remained clinically well with a normal LCI at 3 months following complete cessation of corticosteroids. Azithromycin was ceased with a plan for future cessation of fluticasone/salmeterol. Novelty & Importance Our patient presented 3 months after SOT with clinical and radiographic changes consistent with small airways disease, and a pathological diagnosis of follicular bronchiolitis (FB). FB is a pathological diagnosis characterized by proliferation of bronchus-associated lymphoid tissue with resultant peribronchial follicles. It is associated with multiple etiologies, including infection, autoimmune disease and immunodeficiency. However, it has also been described in lung transplant recipients presenting with bronchiolitis obliterans syndrome (BOS). To our knowledge, this is the first description of FB following pediatric non-lung SOT. Despite extensive testing, including molecular chimerism testing, no clear cause of FB was identified. She responded well to standard BOS treatment with corticosteroids, azithromycin and fluticasone/salmeterol. This case supports investigation and treatment for BOS in this setting. This abstract is funded by: None
2025-05-20 | Vitamin K deficiency bleeding and optimal prophylaxis methods in biliary atresia: A surveillance study in Japan.
Vitamin K (VK) prophylaxis refers to the administration of VK to newborns to prevent neonatal VK deficiency bleeding (VKDB), which is characterized by intracranial hemorrhage (ICH). This study investigated the relationship between VK prophylaxis methods and VKDB in biliary atresia (BA). The survey targeted 497 cases in the Japanese Biliary Atresia Registry between 2015 and 2019, of which 395 (79.5%) returned the questionnaire. Of the 395 patients, 289 were selected after excluding cases in which the gestational age was <36 weeks or the VK prophylaxis methods/feeding contents were unknown. The patients were categorized into two groups according to VK prophylaxis methods. We conducted a comparative study using propensity score matching. The prognosis of patients with or without ICH was also investigated. In the analysis, no VKDB occurred in patients using the 3-month method. In the propensity score matching analysis, age at first visit and age at surgery were later in the three-times method (p = 0.018 and p = 0.022, respectively); VKDB was higher in the three-times method than in the 3-month method (p = 0.029). ICH, jaundice disappearance, cholangitis, and native liver survival rates (NLSRs) were not significantly different between groups. When examining the prognosis based on ICH occurrence, the two groups showed no significant differences in jaundice disappearance, cholangitis, and NLSRs. The ICH group had a greater number of cases of delayed mental and/or motor development. In BA, the 3-month method is effective in preventing VKDB, and early diagnosis is crucial.
2025-03-30 | Passenger Lymphocyte Syndrome with Hepatic Sinusoidal Obstruction Syndrome in an Infant Following Living Donor Liver Transplantation: An Association or Coincidence?
A 7-month-old male infant with AB blood type, diagnosed with biliary atresia and uncompensated cirrhosis postKasai procedure, underwent living donor liver transplantation with a 260-g left lateral segment graft from a blood type B donor. Intraoperatively, the patient received a transfusion of type AB red blood cells. Immunosuppressive therapy included tacrolimus and prednisone. The recovery period was uneventful until postoperative day 18, when the patient developed a fever, changed mental status, and impaired liver functions. Further tests revealed an increased bilirubin level, decreased hemoglobin and platelet counts, detectable anti-A antibodies, and a positive direct Coombs test. A considerable increase in B lymphocytes indicated a diagnosis of passenger lymphocyte syndrome (PLS), which was managed with adjustments to immunosuppression, intravenous immunoglobulin infusion, type B red blood cell transfusion, and supportive care. Interestingly, 1 month after the diagnosis of PLS, a routine computed tomography angiography showed an enlarged liver with patchy enhancement and obscured hepatic veins. Based on the presence of ascites, the clinical diagnosis of hepatic sinusoidal obstruction syndrome (HSOS) was established. Management included transitioning from tacrolimus to cyclosporine and administering low-molecular-weight heparin injections. The condition of the patient improved over 3 weeks, and subsequently, the patient was discharged. To conclude, this report raises the question of a potential correlation between PLS and HSOS in this patient. While PLS is not presently recognized as an established cause of HSOS, the lymphocyte proliferation and antibody production found in PLS can potentially damage the hepatic sinusoidal endothelial cells.
2025-01-22 | Recent advances in the management of pediatric cholestatic liver diseases.
Pediatric cholestatic liver diseases are rare conditions that can result from multiple specific underlying etiologies. Among the most common etiologies of pediatric cholestatic liver diseases are biliary atresia, Alagille syndrome (ALGS), and inherited disorders of bile acid transport. These diseases are characterized by episodic or chronic unremitting cholestasis. Due to the chronicity of these conditions, it is imperative to optimize medical management to improve patient quality of life, provide nutritional support, and reduce bile acid toxicity in efforts to slow disease progression. Cholestatic liver diseases remain the leading cause of pediatric liver transplantation, as many underlying disease etiologies have no curative medical therapies. In the present review, we provide an update on the nutritional, medical, and surgical management of pediatric cholestatic liver diseases. As recent advances have occurred in the field with the addition of ileal bile acid transporter (IBAT) inhibitors, we also review the results from prospective clinical trials, including their strengths and limitations. While recent clinical trials have demonstrated improved pruritus using IBAT inhibitors in ALGS and progressive familial intrahepatic cholestasis, establishing medical therapies proven to slow disease progression remains an area of unmet need.
cell therapies
2025-03-28 | Liver transplantation in children: pre-transplantation preparation tactics
Liver transplantation (LT) from a living related donor is the only life-saving option for children with congenital liver diseases such as biliary atresia, Alagille syndrome, progressive familial intrahepatic cholestasis, and Byler disease, as well as metabolic disorders and acute or chronic liver failure. The development of LT from living related donors significantly reduces the waiting time for a donor organ. The success of the procedure largely depends on the quality of pre-transplantation preparation (PTP) of both donor and recipient. Aim - to study the features of PTP in children with cholestatic liver diseases for successful LT. Materials and methods. 37 children with biliary atresia underwent PTP between 2005 and 2023. In 36 cases, LT was performed using a living related donor; in one case, split-liver transplantation (SPLIT-LT) was used. PTP lasted 3–6 months and included infection focus sanitation, correction of congenital anomalies, emergency status assessment, and evaluation of physical and psycho-emotional development. All examinations followed current international standards. Results. All transplantations were successful. After PTP, improvements were observed in hematological parameters, functional and neuropsychological development, and reduced anxiety levels. All transplant centers acknowledged the high quality of PTP; no child was refused transplantation due to inadequate preparation. The key readiness criteria were a compensated clinical state and a safe bacterial environment. Conclusions. Compliance with regulatory standards and protocols for PTP ensures successful pediatric LT and protects donor health. PTP improves hematological, somatic, and psycho-emotional indicators, reduces risks, and increases the effectiveness of transplantation. Our experience with PTP aligns with international standards. The research was carried out in accordance with the principles of the Declaration of Helsinki. Informed consent of the child and child's parents was obtained for the research. No conflict of interest was declared by the author.
2024-09-01 | P.484: Liver transplant in a patient with syndromatic bile atresia without polysplenia case report.
Introduction: Biliary atresia (BA) is obliterative cholangiopathy with an incidence of 1: 10,000-15,000 live births. Syndromic BA is associated with other congenital anomalies, such as interruption of the inferior cava vein, preduodenal portal vein, abnormal intestinal rotation, complete visceral transposition, cardiac anomalies and polysplenia, this occurs in 10% of patients, it´s believed that there is a relationship between BA and maternal diabetes. Objective: to present the experience of a patient with syndromatic bile duct atresia and a related living donor liver transplant (LDLT). Clinical report: Female, with maternal history of type II diabetes, 1 year 6 months old, started suffering from Cholestatic jaudince at 15 days of life, after the work-up for jaundice, the diagnosis of type III BA was made, plus another clinical features malrotation, pre-duodenal portal vein, cardiac anomalie Intraventricular septal defect: mean muscular intraventricular communication of 1.7 mm, shunt from left to right with a gradient of 60 mm without hemodynamic repercussion, patent foramen ovale of 2 mm and dyslipidemia. Despite the kasai, he did not have bile clearance, with little growth with a weight of 7.5 kg an addition to worsening liver failure with a CHILD – PUGH B with 7 pounts and PELD 24 pounts, so it was decided to perform an LDLT. During the surgical event, the following findings were reported: annular pancreas with preduodenal portal vein, single kidney-shaped spleen without polysplenia, agenesis of the retrohepatic cava, agenesis of the celiac trunk, left hepatic artery coming from the left gastric artery, direct gastric artery from the aorta, right hepatic artery coming from the superior mesenteric artery and incomplete intestinal malrotation. The transplant was performed successfully, as well as a prophylactic appendectomy and placement of a biodegradable biliary stent in the roux. In his post-surgical evolution, he presented partial thrombosis of the portal vein in hepatic segment II, which resolved favorably with anticoagulation in the first 2 days. after LT (LT). Conclusion: The anatomical variants of a syndromatic atresia require great knowledge and vascular control so as not to lose the only possibility of arterial and portal anastomosis that the patient has, in this case the total release of the portal vein without injuring the pancreas or the duodenum represented a challenge. We present our successful experience in the complex surgical approach to a liver transplant with syndromatic atresia. Dra Nidia de Monserrat Arreola.
2023-12-15 | Living donor liver transplantation: 35 years of saving lives
The first liver transplantation was performed by Thomas E Starzl in a child with biliary atresia in 1963.1Starzl TE Marchioro TL Vonkaulla KN Hermann G Brittain RS Waddell WR Homotransplantation of the liver in humans.Surg Gynecol Obstet. 1963; 117: 659-676PubMed Google Scholar Despite initial setbacks, longer survival rates followed. The disproportion of donor graft size to recipient size initially posed a problem in paediatric liver transplantation. Several techniques were described to mitigate the issue: first, graft reduction by Bismuth and Houssin in 1984,2Bismuth H Houssin D Reduced-sized orthotopic liver graft in hepatic transplantation in children.Surgery. 1984; 95: 367-370PubMed Google Scholar and then split liver transplantation by Pichlmayr and colleagues in 1988.3Pichlmayr R Ringe B Gubernatis G Hauss J Bunzendahl H Transplantation of a donor liver to 2 recipients (splitting transplantation)—a new method in the further development of segmental liver transplantation.Langenbecks Arch Chir. 1988; 373: 127-130Crossref PubMed Scopus (489) Google Scholar In 1989, Raia and colleagues4Raia S Nery JR Mies S Liver transplantation from live donors.Lancet. 1989; 2: 497Abstract PubMed Scopus (609) Google Scholar described the first two living donor liver transplantations for paediatric recipients. The technique was followed by an ethical dilemma,5McMaster P Live donors and hepatic transplantation.Lancet. 1989; 2: 1042-1043Abstract PubMed Scopus (3) Google Scholar with concerns for donor safety in a more technically challenging surgery compared with living donor kidney transplantation, which was an accepted procedure at the time. Despite these initial concerns, living donor liver transplantations gained momentum, especially in regions where cultural and religious barriers did not allow the use of deceased donor organs. The procedure expanded from paediatric to adult recipients, and from selected recipients to patients with high urgency criteria, thanks to technical advances. These advances included the use of left lobe grafts, right lobe grafts, modified right lobe grafts, and dual grafts in adults to overcome small-for-size syndrome. Other advancements also supported the growth of living donor liver transplantations, including techniques for graft reduction in paediatric liver transplantation, such as hyper-reduction and anterior hepatic resection of the left lateral segment, and the use of true monosegments to avoid large-for-size syndrome. The success of the procedure must be attributed, in part, to the attention given to the surgery and the postoperative care of the donors, as the wellbeing of these altruistic individuals is essential to any living donor programme. A substantial concern is organ trafficking, and the medical community must remain continuously vigilant to combat these activities to maintain public trust in this procedure. 35 years after it was first described, living donor liver transplantation has evolved into an established surgical procedure, and continues to break new ground, with innovations ranging from open donor hepatectomies to laparoscopic and robotic liver resections. The technique has proven to be safe and has saved more than 80 000 lives worldwide since 2000, according to the Global Observatory on Donation and Transplantation. Going forward, exercising continuous vigilance regarding donor health will be essential to ensure continuity and future advancements in living donor liver transplantations. We declare no competing interests.
2021-01-07 | Liver-only Transplantation in a Patient With Complex Congenital Heart Disease: Case Report and Review of the Literature
Patients with liver failure due to or in addition to congenital heart disease (CHD) represent a growing population in need of organ transplantation. Traditionally, these patients received a combined heart and liver transplantation carrying a high risk of perioperative morbidity and mortality.We discuss a patient with complex cyanotic CHD and biliary atresia undergoing liver-only transplantation. Furthermore, a literature study was performed on combined congenital heart and liver disease in the setting of transplantation.We describe a unique case of a patient with severe CHD undergoing orthotopic liver transplantation for biliary atresia. In the literature, congenital malformations affecting different organs seems not that infrequent. Liver-only transplantation has been described in mild CHD, although data in adult patients are scarce. In severe CHD, the liver usually suffers from congestion. The severity of liver disease and reversibility should be estimated to decide on combined heart-liver transplantation.Our case and a review of the literature demonstrate that a patient-tailored approach with liver-only transplantation may be an appropriate alternative to combined heart and liver transplantation in selected cases.
2019-09-18 | Outcomes of paediatric liver transplant for biliary atresia
Despite the widespread use of Kasai Portoenterostomy (KPE) for biliary atresia, more than two thirds of these patients require liver transplant. Liver transplantation is not widely available in South Africa, and Wits Donald Gordon Medical Centre is one of two centres performing paediatric liver transplantation in the country, and the only centre performing living related donor transplants.A retrospective review was performed at the centre. Demographic data were collected, and tabulated. Survival analysis was performed using the Kaplan Meier method. Complication rates were categorised into biliary, vascular and enteric, and classified as early and late.Sixty-seven first time liver transplants were performed for biliary atresia at WDGMC from 2005 to 2017. Sixty-nine percent were female patients and thirty-one percent were male patients. Forty-eight percent of patients under the age of 5 years had a z-score of -2 or worse for mid upper arm circumference (MUAC). One year overall survival of the cohort is 84.5%, and overall graft survival is 82.9%. Overall mortality was 22%, with infection being the most common cause of death.Early referral of all patients with biliary atresia to a paediatric liver transplant centre is essential for early assessment of indications, and medical and nutritional optimisation of patients. Primary liver transplant should be considered for a select group of patients with unique clinical indications.
antibodies
2024-05-01 | ABO Incompatible Living Donor Liver Transplantation in Children: A Single Centre Experience from India
Background In recent years, paediatric ABO incompatible (ABOi) living donor liver transplant (LT) has shown promising outcomes and can potentially eliminate organ shortage. This study aims to report paediatric ABOi LT experience, including short- and long-term outcomes. Methods It is a single-centre retrospective study. Out of 108 LTs, 20 were done in children. We compared the outcomes between ABOi (n = 20) and non-ABOi (n = 220) paediatric living donor liver transplantation (LDLT) performed during the study period. All the children received pre-LT desensitization therapy comprising rituximab and plasmapheresis targeting pre-LT isohemagglutinin (IHA) titres of ≤1:16. Results Out of 239 paediatric LDLTs from 2017 to 2022, 19 children (11 females) underwent 20 ABOi LTs (including one retransplant with an ABOi domino allograft) at a median age of 12 (12, 51) months, with the majority being biliary atresia (60%). The median change in CD19 cell%, CD20 cell%, and IHA titres after rituximab from day −14 to day −1 (before LT) was satisfactory. In the first 3 months following LT, acute cellular rejection, culture-proven sepsis, and biliary and vascular complications were seen in 10%, 20%, 20%, and 15%, respectively. None of the ABOi LT recipients developed antibody-mediated rejection. ABOi LT recipients, as compared to non-ABOi LT recipients, had a higher incidence of bile leaks and prolonged hospital stay, with the rest of the complications, including biliary strictures and long-term outcomes, being comparable. At a median follow-up of 21 (14, 33) months, 4 children expired (21%). Conclusion ABOi LT in children shows excellent outcomes and can be performed safely with prior desensitization when a compatible liver is unavailable. In recent years, paediatric ABO incompatible (ABOi) living donor liver transplant (LT) has shown promising outcomes and can potentially eliminate organ shortage. This study aims to report paediatric ABOi LT experience, including short- and long-term outcomes. It is a single-centre retrospective study. Out of 108 LTs, 20 were done in children. We compared the outcomes between ABOi (n = 20) and non-ABOi (n = 220) paediatric living donor liver transplantation (LDLT) performed during the study period. All the children received pre-LT desensitization therapy comprising rituximab and plasmapheresis targeting pre-LT isohemagglutinin (IHA) titres of ≤1:16. Out of 239 paediatric LDLTs from 2017 to 2022, 19 children (11 females) underwent 20 ABOi LTs (including one retransplant with an ABOi domino allograft) at a median age of 12 (12, 51) months, with the majority being biliary atresia (60%). The median change in CD19 cell%, CD20 cell%, and IHA titres after rituximab from day −14 to day −1 (before LT) was satisfactory. In the first 3 months following LT, acute cellular rejection, culture-proven sepsis, and biliary and vascular complications were seen in 10%, 20%, 20%, and 15%, respectively. None of the ABOi LT recipients developed antibody-mediated rejection. ABOi LT recipients, as compared to non-ABOi LT recipients, had a higher incidence of bile leaks and prolonged hospital stay, with the rest of the complications, including biliary strictures and long-term outcomes, being comparable. At a median follow-up of 21 (14, 33) months, 4 children expired (21%). ABOi LT in children shows excellent outcomes and can be performed safely with prior desensitization when a compatible liver is unavailable.
2022-02-02 | Transplant-associated thrombotic microangiopathy and acquired nephrotic syndrome: A case report in a 35-month child.
Abstract Background Transplant-associated thrombotic microangiopathy (TA-TMA) presents with thrombocytopenia, nonimmune hemolytic anemia, peripheral blood schistocytes and end-organ damage to the kidney. TA-TMA is associated with a significant increased morbidity and mortality, especially when treatment is not initiated early. We present a pediatric clinical case of a 35-month child with history of hepatic transplantation, who develop the clinical spectrum of TA-TMA and acquired nephrotic syndrome. Case presentation: A 35-month-old boy with history of hepatic transplantation secondary of atresia of biliary ducts who received immunosuppressive therapy with tacrolimus, mycophenolate and steroids. He presents with 4 days of fever, vomiting, and non-dysenteric diarrhea. He received an initial course of antibiotics without response. After 3 days he continues with fever, low urine output and edema. Vital signs showed high blood pressure and physical exam revealed facial and extremity edema. Laboratory results showed proteinuria and hematuria, low albumin, and high triglycerides. All possible etiologies of nephrotic syndrome were ruled out. Kidney biopsy showed TMA changes. Plasma exchange and Eculizumab were started with clinical improvement. Discussion TMA can be classified as a primary or secondary. Primary TMA can be hereditary or acquired. Acquired TMA included the ones triggered by medications. This clinical syndrome has been described as an endothelial dysfunction secondary of an immune reaction over the endothelium and/or a direct cytotoxic effect over endothelium and platelets. In this case report the use of calcineurin inhibitors (tacrolimus) one of the most common drugs associated with TMA was one the triggers factors. Recent publications have described how these patients that are exposed to any triggers has also a genetically predisposing to develop TMA. There is a lack in diagnostics and prognostic markers. The earliest treatment is stared, the better prognosis and outcomes.
2019-05-01 | 2. Answering the Donor Graft Shortage - Successful Outcome of ABO Incompatible Pediatric Living Related Liver Transplants
Background and Aims: ABO-incompatible (ABOi) liver transplantation is usually contraindicated because of risk of antibody-mediated humoral rejection of graft. Ours is a busy living related liver transplant (LDLT) center. We describe 8 successful cases of patients who had LDLT from ABOi donors. Methods: Study period-July 2010 to April 2018. ABOi LDLT patients <18 years age. Protocol consisted of rituximab 2 weeks prior (>3 years) and plasmapheresisbefore LDLT. Target anti ABOtitres pre-transplant was less than 1:16. Plasmapheresis to aim anti-ABO titers below 1:32 was planned up to 4 weeks post-op. Mycophenolate was started one week prior to transplant. No child was splenectomized and no local graft infusion used. Standard triple immune suppression (Steroid, Mycophenolate Mofetil and Tacrolimus) was used post operatively. Results: Out of 200 Pediatric LDLT patients, 8 were ABO incompatible (ABOi). Indications- Biliary Atresia- 4; PFIC – 2, Chronic rejection 1 (re-transplant), Alagille syndrome. Median age 31 months (7–91); median PELD score 24 (19–42). Mean graft-to-recipient weight ratio 2.1. Initial range of isoagglutinin IgM and IgG titers were 1:32–1:256 and 1:64–1:256 respectively in 6 patients on whom 2–4 cycles of cascade plasmapheresis done preoperatively. One patient had titre 1:1024 where immune adsorption technique was used in view of 3 failed plasmapheresis along with Rituximab. Another 1 patient underwent urgent transplant in whom Immunoadsorption technique was used. Postoperative IVIG was used in 2 patients. Postoperative complications included portal vein thrombosis (one-successfully re-explored), bacterial infection (one), fungal infection (one) and CMV infection (one) based on culture reports. Mean hospital stay was 26 days (15–59 range). Patient and graft survival was 100% in recipients at a mean follow-up of 33 months (range 2–80 months). Conclusions: ABO-incompatible LDLT can be safely performed in children with excellent outcome. Preoperative reduction of antibody titres<1:32 by plasmapheresis is essential for successful LT. Immuno-adsorption (glycosorb) technique is more effective than routine cascade plasmapheresis in patients with very high antibody titres. The authors have none to declare.
2018-07-01 | 10. Successful outcome of ABO incompatible pediatric living related liver transplant using the standard immunosuppression
Background and Aims: ABO-incompatible (ABOi) liver transplantation is usually contraindicated because of risk of antibody-mediated humoral rejection of graft. Ours is a busy living related liver transplant (LDLT) center. We describe 6 successful cases of patients who had LDLT from ABOi donors. Methods: Study period-July 2010 to April 2018. ABOi LDLT patients <18 years age. Protocol consisted of rituximab 2 weeks prior (>3 years) and plasmapheresis before LDLT. Target anti ABO titres pre-transplant was less than 1:16. Plasmapheresis to aim anti-ABO titers below 1:32 was planned upto 4 weeks post-op. Mycophenolate was started one week prior to transplant. No child was splenectomized and no local graft infusion used. Standard triple immune suppression (Steroid, Mycophenolate Mofetil and Tacrolimus) was used post operatively. Results: Out of 200 Pediatric LDLT patients, 7 were ABO incompatible (ABOi). Indications- Biliary Atresia- 4; PFIC – 2, Chronic rejection 1 (re-transplant). Median age 33 months (7–91); median PELD score 24 (19–42). Mean graft-to-recipient weight ratio 1.79. Initial range of isoagglutinin IgM and IgG titers were 1:32–1:256 and 1:64–1:256 respectively in 6 patients on whom median 4 (range 2–6) cycles of plasmapheresis done. One patient had titre 1:1024 where immune adsorption technique was used in view of 3 failed plasmapheresis along with Rituximab. Postoperative IVIG was used in 2 patients. No rejection, bacterial or fungal infections noted. Postoperative complications included portal vein thrombosis (one-successfully re-explored) and CMV infection (one). Mean hospital stay was 19 days (18–23 range). Patient and graft survival was 100% in recipients at a mean follow-up of 24 months (range 1–59 months). Conclusions: ABO-incompatible LDLT can be safely performed in children. Preoperative reduction of antibody titres <1:32 by plasmapheresis is essential for successful LT. Immuno-adsorption (glycosorb) technique is more effective than routine cascade plasmapheresis in patients with very high antibody titres. The authors have none to declare.
2017-11-22 | Large-scale proteomics identifies MMP-7 as a sentinel of epithelial injury and of biliary atresia
Biliary atresia is a progressive infantile cholangiopathy of complex pathogenesis. Although early diagnosis and surgery are the best predictors of treatment response, current diagnostic approaches are imprecise and time-consuming. We used large-scale, quantitative serum proteomics at the time of diagnosis of biliary atresia and other cholestatic syndromes (serving as disease controls) to identify biomarkers of disease. In a discovery cohort of 70 subjects, the lead biomarker was matrix metalloproteinase-7 (MMP-7), which retained high distinguishing features for biliary atresia in two validation cohorts. Notably, the diagnostic performance reached 95% when MMP-7 was combined with γ-glutamyltranspeptidase (GGT), a marker of cholestasis. Using human tissue and an experimental model of biliary atresia, we found that MMP-7 is primarily expressed by cholangiocytes, released upon epithelial injury, and promotes the experimental disease phenotype. Thus, we propose that serum MMP-7 (alone or in combination with GGT) is a diagnostic biomarker for biliary atresia and may serve as a therapeutic target.
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