Clinical implications of serum Mac-2-binding protein (M2BPGi) during regular follow-up of patients with biliary atresia

This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/S00383-018-4317-2Purpose: The Mac-2-binding protein glycosylation-modified isomer (M2BPGi) is a new marker for progression of hepatic fibrosis. We examined the relationship between serum M2BPGi levels and liver histological findings in patients with biliary atresia (BA) who were not transplant candidates. Methods: Patients with BA who were not transplant candidates with good liver function were included. We examined M2BPGi levels and histological findings in relation to other laboratory markers of liver fibrosis, including aspartate aminotransferase (AST) to platelet ratio index, fibrosis-4 index, and type IV collagen 7s domain. Liver fibrosis was evaluated based on the METVIR score. Results: 37 patients were included. The median age was 18 years (range 3–38 years). M2BPGi values ranged from 0.3 to 6.9 cutoff index (COI) (median 1.6). The degree of liver fibrosis varied with M2BPGi level. For predicting cirrhosis (F4) and advanced liver fibrosis (≥ F3), M2BPGi had higher areas under the curve (AUCs; 0.93, respectively) with cutoff COIs of 1.84 and 1.67, respectively, than for the four conventional markers for fibrosis. Conclusion: M2BPGi is a novel marker for liver fibrosis in patients with BA. It is especially useful for following patients with BA with a native liver and supporting liver biopsy interpretation findings

Balloon dilatation for congenital esophageal stenosis associated with esophageal atresia

The version of record of this article, first published in Pediatric Surgery International, is available online at Publisher’s website: https://doi.org/10.1007/s00383-024-05652-w.Purpose: Congenital esophageal stenosis (CES) associated with esophageal atresia (EA) is rare, and no standard treatment has been established. We reviewed cases of EA-associated CES to assess the clinical characteristics and treatment outcomes, especially the feasibility of endoscopic dilatation. Methods: We retrospectively examined patients with EA-associated CES. We also compared treatment outcomes of EA-associated CES with those of EA patients without CES who developed postoperative anastomotic stricture. Results: Among 44 patients with EA, ten had CES (23%). Postoperative complications were not significantly different between EA patients with CES and those without CES but with anastomotic stricture. All CES patients underwent balloon dilatation as initial treatment. Eight of nine patients (89%) were successfully treated by dilatation only, and one patient underwent surgical resection. The median number of balloon dilatations for CES was five (2–17), which was higher than that for anastomotic stricture in patients without CES (p = 0.012). Esophageal perforation occurred in five patients with CES (5/9, 56%) after dilatation, but all perforations were successfully managed conservatively with an uneventful post-dilatation course. Conclusions: Twenty-three percent of patients with EA had CES. Although balloon dilatation for EA-associated CES required multiple treatments and carried a risk of perforation, balloon dilatation showed an 89% success rate and all perforations could be managed conservatively

Serum Mac-2-binding protein (M2BPGi) as a marker of chronological liver fibrosis in biliary atresia patients with cirrhosis

This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s00383-019-04535-9Purpose: Biliary atresia (BA) is characterized by progressive liver fibrosis, but it is difficult to assess the progression after the patient develops cirrhosis. Mac-2-binding protein glycosylation isomer (M2BPGi) is a new marker for hepatic fibrosis. We examined the chronological changes in M2BPGi levels in BA patients with cirrhosis. Methods: Patients with cirrhosis were selected from among pediatric BA patients who had their native livers. Serum M2BPGi levels and Child–Pugh classification were evaluated. A total of 11 pediatric BA patients with cirrhosis were recruited. Results: Initial M2BPGi level after diagnosis of liver cirrhosis based on liver biopsy was on average 3.4, and the most recent M2BPGi level under observation was on average 4.3. The follow-up period from the initial M2BPGi measurement averaged 22.6 months. The ratio of the initial and most recent values (M2BPGi ratio) was on average 1.3 (0.5–2.4). Three cases with improved fibrosis (M2BPGi ratio < 1.0) remained in Child A, as did six cases (1.0 ≤ M2BPGi ratio < 2.0), but two cases with marked fibrosis progression (2.0 ≤ M2BPGi ratio) advanced to decompensated cirrhosis Child B. Conclusion: M2BPGi is useful as a prognostic factor for BA patients with liver cirrhosis. In addition, fibrosis improved even after the development of cirrhosis

Effect of microscopy-assisted portoenterostomy (MAPE) for biliary atresia

This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s00383-020-04794-x.Purpose: Portoenterostomy (PE) is the standard treatment for biliary atresia (BA). However, micro-bile ducts are difficult to identify with surgical loupes and dissect systematically. We report the effects of our attempts to dissect hilar tissue using a surgical microscope. Methods: Microscopy-assisted portoenterostomy (MAPE) was initiated in 2014. Patients born between 2000 and 2013 who underwent PE until day 70 without a surgical microscope for BA were gathered as historical control. MAPE in re-do PE cases (Re-MAPE) was evaluated in the same manner. Results: Ten patients underwent MAPE for BA during the study period. 17 patients in the conventional PE group were gathered. In the MAPE group, the jaundice clearance rate was 80%, compared with 53% in the conventional PE group. Re-MAPE was performed in four patients, who had a jaundice clearance rate of 75%, essentially identical to the rate with initial MAPE. At age 4 years, the native liver survival rate was 58% in the MAPE group and 38% in the conventional PE group. The native liver survival rate in the Re-MAPE group was 75%. Conclusion: MAPE is useful for sharing the surgical field during open PE in patients with BA. It may improve the rate of jaundice clearance

One Year of Preemptive Valganciclovir Administration in Children After Liver Transplantation

Ueno T., Kodama T., Noguchi Y., et al. One Year of Preemptive Valganciclovir Administration in Children After Liver Transplantation. Transplantation Proceedings 52, 1852 (2020); https://doi.org/10.1016/j.transproceed.2020.01.163.Objectives: Valganciclovir (VGCV) is used as prophylaxis against cytomegalovirus (CMV) infection after pediatric living donor liver transplantation (LDLT). The purpose of this study was to examine the efficacy of 1 year of preemptive VGCV administration compared with a shorter administration after pediatric LDLT. Methods: VGCV was administered to 56 children who underwent LDLT. CMV and Epstein-Barr virus (EBV) antibody status, pp65 antigenemia, and other laboratory data were assessed at 1 year after LDLT. Patients were divided into the 1-year group (n = 32) (patients who had 1 year of VGCV administration) and the <1-year group (n = 24) (patients who had less than 1 year of VGCV administration). Results: Study participants consisted of 34 females and 22 males, with a mean age of 4.2 years at transplant. Regarding pretransplant donor (D)/recipient (R) CMV antibody status, 13 were D positive (+)/R negative (-), 27 were D+/R+, 8 were D-/R+, and 8 were D-/R-. For EBV, 22 were D+/R+, 32 were D+/R-, and 2 were D-/R-. In the 1-year group, only 2 patients (6.5%) developed CMV infection, whereas 8 patients (33.3%) developed CMV infection in the <1-year group. The CMV pp65 antigenemia assay was positive in 2 patients. CMV IgM was positive in 7 patients. One year of preemptive VGCV administration was associated with a lower incidence of CMV infection (P = .008), but not EBV infection. No adverse effects were observed. Conclusions: One year of preemptive VGCV administration after LDLT is safe and suppresses CMV infection. It was useful after pediatric LDLT

Treatment and follow-up of late onset intra hepatic bile duct stones in congenital biliary dilatation

This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s00383-022-05321-w.Purpose: The postoperative course after surgery for congenital biliary dilatation (CBD) has some complications. Intrahepatic bile duct (IHBD) stones were known as a late complication. We report on the treatment and long-term follow-up of postoperative IHBD stones in our department. Methods: Patients who underwent CBD surgery at age 15 years or younger in our department were identified. Those followed up for 5 years or more were enrolled. Annual blood chemistry tests and abdominal ultrasonography were performed. Each patient’s surgical procedure, IHBD stone diagnosis, treatments, and outcomes were retrospectively assessed. Results: Fifty-one patients were analyzed. The median age at the last visit was 24 years (range 7–45 years), and the median age at CBD surgery was 3 years. Eight patients (16%) developed late-onset IHBD stones. The median age at onset was 25 years, and the median duration after surgery was 20 years. The initial treatment was double-balloon enteroscopy (DBE) in 4 cases, which resulted in stone removal in 3 of the 4 patients (75%). Conclusion: Since CBD may cause late-onset IHBD stones, continuous follow-up is required even in adulthood. In this study, DBE was effective and minimally invasive, and it is recommended as the initial treatment

Early Use of Everolimus as a Third Immunosuppressive Agent for Intestinal Transplantation: A Report of 2 Cases

Ueno T., Toyama C., Deguchi K., et al. Early Use of Everolimus as a Third Immunosuppressive Agent for Intestinal Transplantation: A Report of 2 Cases. Transplantation Proceedings 54, 472 (2022); https://doi.org/10.1016/j.transproceed.2022.01.010.Background: In patients with intestinal transplantation (ITx), renal function is easily impaired because of long-term parenteral nutrition and side effects of tacrolimus. Everolimus was used in patients with renal insufficiency in our study. Methods: We administered everolimus as a third immunosuppressive agent in addition to tacrolimus and steroids for renal sparing in patients who received ITx. We assessed everolimus levels, complications, and renal function. Results: Two patients received everolimus after ITx. Patient 1 was a 13-year-old boy who underwent ITx for an allied disorder of Hirschsprung's disease. After induction therapy with rabbit antithymocyte globulin, maintenance therapy consisted of tacrolimus and steroids. Everolimus was introduced 3 months after ITx for renal sparing. Seven months later, the patient required partial intestinal graft resection owing to bowel obstruction. Everolimus was suspended for only 2 weeks. Four years after ITx, the trough level of tacrolimus was maintained at 3 to 5 ng/mL. The trough level of everolimus was maintained at 3 to 5 ng/mL. Patient 2 was a 32-year-old man who underwent deceased ITx for short gut syndrome. Induction and maintenance immunosuppression was the same as for patient 1. Everolimus was introduced 1 month after surgery. Two years after ITx, trough levels of tacrolimus and everolimus were the same as in patient 1. No rejection was observed in either patient, and renal function was well maintained. We observed no side effects caused by everolimus. Conclusions: Everolimus could be used safely and effectively after ITx. Early use of everolimus after ITx did not affect wound healing

Impact of Monosegment Graft Use for Infants in Pediatric Living Donor Liver Transplantation

Ueno T., Toyama C., Deguchi K., et al. Impact of Monosegment Graft Use for Infants in Pediatric Living Donor Liver Transplantation. Transplantation Proceedings 54, 391 (2022); https://doi.org/10.1016/j.transproceed.2021.12.034.Background: Left lateral segment grafts are generally used for very young pediatric patients undergoing living donor liver transplantation (LDLT). Recently, graft reduction techniques were developed for LDLT. Monosegment grafting has been used in newborns. The aim of this study was to determine the usefulness of monosegment grafting for infants. Methods: Recipients <2 years of age who underwent LDLT with a monosegment graft between 2010 and 2020 were gathered. Parents comprised all LDLT donors. A segment 2 monosegment graft was resected as a graft from the donor. Standard liver volume (SLV) was estimated using Urata's equation. Graft type, graft weight (GW), and native liver weight were assessed. Results: Eight patients were included in the study. Original diseases consisted of biliary atresia (n = 6) and fulminant hepatitis (n = 2). Final graft type included monosegment (n = 5) and reduced monosegment (n = 3). Median final GW/body weight after reduction was 3% (range, 2%-3.4%). Median native liver weight/SLV was 134% except in patients with fulminant hepatitis. Median pre-reduction graft volume (GV)/estimated GV was 113% (range, 60%-208%). Median pre-reduction GV/SLV of monosegment grafts that required reduction (n = 3) was 109% (range, 106%-121%). Median final reduced graft GV/SLV was 80% (range, 74%-91%). Complications due to large-for-size grafts were not observed. One case of bile leakage due to graft reduction occurred as a complication. Grafts were functioning well with the exception of one graft loss due to antibody-mediated rejection. Conclusion: Estimated GV in infants varies widely. Monosegment grafting can be useful for infants as well as newborns

Long-Term Outcome of Portal Vein Stenting After Pediatric Living Donor Liver Transplantation

Ueno T., Toyama C., Deguchi K., et al. Long-Term Outcome of Portal Vein Stenting After Pediatric Living Donor Liver Transplantation. Transplantation Proceedings 54, 454 (2022); https://doi.org/10.1016/j.transproceed.2022.01.008.Background: Portal vein (PV) stenosis is sometimes seen in pediatric living donor liver transplantation (LDLT). PV stents have been attempted in adults with persistent stenosis. However, long-term usefulness of PV stenting is unknown because stents do not expand with growth. We investigated the effect and long-term outcome of PV stenting for stenosis after pediatric LDLT. Methods: We included patients aged <18 years who underwent LDLT from 1998 to 2020 and who underwent PV stenting for stenosis. We assessed age at procedure, stent complications, and long-term outcomes. Results: Five patients underwent PV stent placement. The median age at LDLT was 10 years (range, 0.8-18.1 years). The median interval between LDLT and stent placement was 25 months. The median age at stent placement was 16 years (range, 3-20 years). The median body weight was 38 kg (range, 13-63 kg). The median stent diameter was 8 mm. The median observation period after stent placement was 8 years. On average, body weight increased 1.6 times. One complication associated with stent placement was PV thrombosis, which resulted in stent failure, but we observed no portal hypertension. In the other 4 patients, the stent has remained functioning, and there was no clinical evidence of portal hypertension. Conclusions: PV stents are effective for intractable PV stenosis in children. PV stents were successfully placed in children as young as 3 years old and weighing 13 kg. Our data suggests that a stent placed in young children does not cause portal hypertension as patients grow

Serum Trough Concentration and Effects of Mycophenolate Mofetil Based on Pathologic Findings in Infants After Liver Transplantation

Ueno T., Kodama T., Noguchi Y., et al. Serum Trough Concentration and Effects of Mycophenolate Mofetil Based on Pathologic Findings in Infants After Liver Transplantation. Transplantation Proceedings 52, 1855 (2020); https://doi.org/10.1016/j.transproceed.2020.01.160.Objectives: Mycophenolate mofetil (MMF) is mainly used in conjunction with calcineurin inhibitors as an additional immunosuppressive for renal sparing after liver transplantation. However, few reports about MMF use in infants after living donor liver transplantation (LDLT) are available. The purpose of this study was to examine the efficacy and safety of MMF in infants. Methods: This study enrolled infants younger than 1 year of age who received LDLT at our institution. Patients received oral MMF twice daily. The initial dose was 40 to 50 mg/kg/d, which was increased to a target mycophenolic acid (MPA) trough level of 2 mg/L. Body weight, height, MMF dose, MPA trough level, acute cellular rejection (ACR) episodes, pathologic findings, and adverse effects were analyzed. Allograft fibrosis was graded using the Meta-analysis of Histological Data in Viral Hepatitis score. Results: Patients received MMF for refractory ACR (n = 2), fulminant hepatitis (n = 2), and pre-existing antibodies (n = 1). Original diseases were biliary atresia (n = 3) and fulminant hepatitis (n = 2). Mean age at transplant was 8 months (range 3-10 months). The last available mean trough level was 2.7 mg/L. The mean dose was 66 mg/kg/d or 1429 mg/m2/d at the time of the last available through level. The regression line for MMF dose and MPA trough level was y = 1.8 × 10-3x. The correlation coefficient was 0.65. All allografts showed F1 to F2 fibrosis. Two patients discontinued MMF because of infection and bone marrow suppression, respectively. Two patients converted to everolimus. One patient continued on MMF. Conclusions: After LDLT, infants require a higher MMF dose than older patients based on trough levels, but allograft fibrosis can progress