Identification of liver transplant biopsy phenotypes associated with distinct liver biological markers and allograft survival.

The intricate association between histologic lesions and circulating antihuman leucocyte antigen donor-specific antibodies (DSA) in liver transplantation (LT) requires further clarification. We conducted a probabilistic, unsupervised approach in a comprehensively well-annotated LT cohort to identify clinically relevant archetypes. We evaluated 490 pairs of LT biopsies with DSA testing from 325 recipients transplanted between 2010 and 2020 across 3 French centers and an external cohort of 202 biopsies from 128 recipients. Unsupervised archetypal analysis integrated all clinico-immuno-histologic parameters of each biopsy to identify biopsy archetypes. The median time after LT was 1.17 (interquartile range, 0.38-2.38) years. We identified 7 archetypes distinguished by clinico-immuno-histologic parameters: archetype #1: severe T cell-mediated rejection (15.9%); #2: chronic rejection with ductopenia (1.8%); #3: architectural and microvascular damages (3.5%); #4: (sub)normal (55.9%); #5: mild T cell-mediated rejection (4.9%); #6: acute antibody-mediated rejection (6.5%); and #7: chronic rejection with DSA (11.4%). Cell infiltrates vary in the archetype. These archetypes were associated with distinct liver biological markers and allograft outcomes. These findings remained consistent when stratified using the patient's age or indications for LT, with good performance in the external cohort (mean highest probability assignment = 0.58, standard deviation ± 0.17). In conclusion, we have identified clinically meaningful archetypes, providing valuable insights into the intricate DSA-histology association, which may help standardize liver allograft pathology classification.

Surgical Management of Wilms Tumors with Intravenous Extension: A Multicenter Analysis of Clinical Management with Technical Insights.

BACKGROUND: About 5% of Wilms tumors present with vascular extension, which sometimes extends to the right atrium. Vascular extension does not affect the prognosis, but impacts the surgical strategy, which is complex and not fully standardized. Our goal is to identify elements of successful surgical management of Wilms tumors with vascular extensions. PATIENTS AND METHODS: A retrospective study of pediatric Wilms tumors treated at three sites (January 1999-June 2019) was conducted. The inclusion criterion was the presence of a renal vein and vena cava thrombus at diagnosis. Tumor stage, pre and postoperative treatment, preoperative imaging, operative report, pathology, operative complications, and follow-up data were reviewed. RESULTS: Of the 696 pediatric patients with Wilms tumors, 69 (9.9%) met the inclusion criterion. In total, 24 patients (37.5%) had a right atrial extension and two presented with Budd-Chiari syndrome at diagnosis. Two died at diagnosis owing to pulmonary embolism. All patients received neoadjuvant chemotherapy and thrombus regressed in 35.6% of cases. Overall, 14 patients had persistent intra-atrial thrombus extension (58%) and underwent cardiopulmonary bypass. Most thrombi (72%) were removed intact with nephrectomy. Massive intraoperative bleeding occurred during three procedures. Postoperative renal insufficiency was identified as a risk factor for patient survival (p = 0.01). With a median follow-up of 9 years (range: 0.5-20 years), overall survival was 89% and event-free survival was 78%. CONCLUSIONS: Neoadjuvant chemotherapy with proper surgical strategy resulted in a survival rate comparable to that of children with Wilms tumors without intravascular extension. Clinicians should be aware that postoperative renal insufficiency is associated with worse survival outcomes.

European Liver Transplant Registry: Donor and transplant surgery aspects of 16,641 liver transplantations in children.

BACKGROUND AND AIMS: The European Liver Transplant Registry (ELTR) has collected data on liver transplant procedures performed in Europe since 1968. APPROACH AND RESULTS: Over a 50-year period (1968-2017), clinical and laboratory data were collected from 133 transplant centers and analyzed retrospectively (16,641 liver transplants in 14,515 children). Data were analyzed according to three successive periods (A, before 2000; B, 2000-2009; and C, since 2010), studying donor and graft characteristics and graft outcome. The use of living donors steadily increased from A to C (A, n = 296 [7%]; B, n = 1131 [23%]; and C, n = 1985 [39%]; p = 0.0001). Overall, the 5-year graft survival rate has improved from 65% in group A to 75% in group B (p < 0.0001) and to 79% in group C (B versus C, p < 0.0001). Graft half-life was 31 years, overall; it was 41 years for children who survived the first year after transplant. The late annual graft loss rate in teenagers is higher than that in children aged <12 years and similar to that of young adults. No evidence for accelerated graft loss after age 18 years was found. CONCLUSIONS: Pediatric liver transplantation has reached a high efficacy as a cure or treatment for severe liver disease in infants and children. Grafts that survived the first year had a half-life similar to standard human half-life. Transplantation before or after puberty may be the pivot-point for lower long-term outcome in children. Further studies are necessary to revisit some old concepts regarding transplant benefit (survival time) for small children, the role of recipient pathophysiology versus graft aging, and risk at transition to adult age.

Predicting Factors of Protracted Intestinal Failure in Children with Gastroschisis.

OBJECTIVE: To identify prenatal and neonatal predictors of short bowel syndrome-related intestinal failure (SBS-IF) in gastroschisis. STUDY DESIGN: This retrospective study included all patients with gastroschisis born between 2000 and 2017 who were enrolled in our home parenteral nutrition program, and all patients with gastroschisis born in our institution who survived 2 weeks, during the same time period. Prenatal ultrasound features, neonatal status, anatomic features, oral feeding, and parenteral nutrition dependency were analyzed. RESULTS: Among 180 patients, 35 required long-term parenteral nutrition (SBS-IF group) and 145 acquired full oral feeding within 6 months (oral feeding group). The mean follow-up was 7.9 years (IQR, 1.6-17.5 years) and 5.0 years (IQR, 0.1-18.2 years), respectively. Both bowel matting (OR, 14.23; 1.07-16.7; P = .039) and secondarily diagnosed atresia or stenosis (OR, 17.78; 3.13-100.98; P = .001) were independent postnatal predictors of SBS-IF. Eighteen children (51% of the SBS-IF group) were still dependent on artificial nutrition at the last follow-up. patients with SBS-IF who achieved full oral feeding had a median residual small-bowel length of 74 cm (IQR, 51-160 cm) vs 44 cm (IQR, 10-105 cm) for those still dependent on artificial nutrition (P = .02). An initial residual small bowel length of more than 50 cm was the best predictive cut-off for nutritional autonomy, with a sensitivity of 67% and a specificity of 100%. CONCLUSIONS: Bowel matting, complex gastroschisis, and secondary intestinal obstruction were associated with SBS-IF in gastroschisis. For patients with SBS-IF, a small bowel length of more than 50 cm was predictive of secondary nutritional autonomy.

Preservation of native sigmoid colon for secondary continent cystostomy after multivisceral transplantation for chronic intestinal pseudo-obstruction.

Chronic intestinal pseudo-obstruction (CIPO) is characterized by severe digestive +/- urinary dysmotility. If the conservative management fails, multivisceral transplantation (MVT) may be needed. However, urinary dysmotility remains after MVT and requires to continue urinary catheterizations and/or drainage. We report on a boy with severe CIPO complicated by (1) chronic intestinal obstruction requiring total parenteral nutrition, decompression gastrostomy, and ileostomy; (2) recurrent line infections; (3) hepatic fibrosis; and (4) distension of the bladder and upper urinary tract, and recurrent urinary infections, leading to non-continent cystostomy for urinary drainage. He underwent MVT at the age of 5 years. The transplant included the liver, stomach, duodenum and pancreas, small bowel, and right colon. The distal native sigmoid colon was preserved. Fifteen months later, he underwent a pull through of the transplanted right colon (Duhamel's procedure), together with a tube continent cystostomy (Monti's procedure) using the native sigmoid. Postoperative course was uneventful, and the remaining ileostomy was closed 3 months later. Five years post-transplant, he is alive and well. He is fed by mouth with complementary gastrostomy feeding at night. He has 3-6 stools per day, with occasional soiling. The cystostomy is used for intermittent urinary catheterization 4 times/day and continuous drainage at night. He is dry, with rare afebrile urinary infections, normal renal function, and un-dilated upper urinary tract. Conclusion: in severe CIPO with urinary involvement, preservation of the distal native sigmoid colon during MVT allows secondary creation of a continent tube cystostomy, which is useful to manage persistent urinary disease.

Outcome of Total Colonic Aganglionosis Involving the Small Bowel Depends on Bowel Length, Liver Disease, and Enterocolitis.

OBJECTIVES: Total colonic aganglionosis involving the small bowel is a rare form of Hirschsprung disease. We aim to analyse the long-term outcomes, digestive autonomy, and complications, to suggest recommendations for prevention and treatment. METHODS: All patients born between 2000 and 2015 followed in our centre were retrospectively included. We analysed the length of aganglionosis, surgical procedures, growth, duration of parenteral nutrition (PN), enterocolitis, liver disease, intestinal transplantation. RESULTS: Twenty-five patients were followed for a median of 10.9 years. Fifteen patients had less than 80 cm of ganglionic small bowel (SB) with a median of 20 cm. Ten patients had more than 80 cm of ganglionic sB with a median of 115 cm. The median PN duration was significantly shorter for patients with more than 80 cm: 0.9 versus 7.5 years in those with less than 80 cm (P  < 0.001). No patient with less than 80 cm was weaned off PN, except 1 who underwent intestinal transplantation. Ten patients with less than 80 cm develop enterocolitis on the excluded segment, leading to emergency entero-colectomy in 5. Liver disease was more frequent in patients with less than 80 cm (11 vs 0). Three patients required combined liver-intestine transplantation; 2 underwent an isolated intestinal transplantation. CONCLUSIONS: Digestive autonomy was possible in most patients with more than 80 cm of ganglionic SB. The more severe complication was enterocolitis. Liver disease compromised long-term survival without transplantation. Both complications should be prevented by early diversion and enterectomy of the whole aganglionic segment. Follow-up in or together with a multidisciplinary intestinal rehabilitation centre is suggested.

Phenotypic switch of smooth muscle cells in paediatric chronic intestinal pseudo-obstruction syndrome.

Smooth Muscle Cells (SMC) are unique amongst all muscle cells in their capacity to modulate their phenotype. Indeed, SMCs do not terminally differentiate but instead harbour a remarkable capacity to dedifferentiate, switching between a quiescent contractile state and a highly proliferative and migratory phenotype, a quality often associated to SMC dysfunction. However, phenotypic plasticity remains poorly examined in the field of gastroenterology in particular in pathologies in which gut motor activity is impaired. Here, we assessed SMC status in biopsies of infants with chronic intestinal pseudo-obstruction (CIPO) syndrome, a life-threatening intestinal motility disorder. We showed that CIPO-SMCs harbour a decreased level of contractile markers. This phenotype is accompanied by an increase in Platelet-Derived Growth Factor Receptor-alpha (PDGFRA) expression. We showed that this modulation occurs without origin-related differences in CIPO circular and longitudinal-derived SMCs. As we characterized PDGFRA as a marker of digestive mesenchymal progenitors during embryogenesis, our results suggest a phenotypic switch of the CIPO-SMC towards an undifferentiated stage. The development of CIPO-SMC culture and the characterization of SMC phenotypic switch should enable us to design therapeutic approaches to promote SMC differentiation in CIPO.

Arterial abnormalities identified in kidneys transplanted into children during the COVID-19 pandemic.

Graft artery stenosis can have a significant short- and long-term negative impact on renal graft function. From the beginning of the COVID-19 pandemic, we noticed an unusual number of graft arterial anomalies following kidney transplant (KTx) in children. Nine children received a KTx at our center between February and July 2020, eight boys and one girl, of median age of 10 years. Seven presented Doppler features suggesting arterial stenosis, with an unusual extensive pattern. For comparison, over the previous 5-year period, persistent spectral Doppler arterial anomalies (focal anastomotic stenoses) following KTx were seen in 5% of children at our center. We retrospectively evidenced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in five of seven children with arterial stenosis. The remaining two patients had received a graft from a deceased adolescent donor with a positive serology at D0. These data led us to suspect immune postviral graft vasculitis, triggered by SARS-CoV-2. Because the diagnosis of COVID-19 is challenging in children, we recommend pretransplant monitoring of graft recipients and their parents by monthly RT-PCR and serology. We suggest balancing the risk of postviral graft vasculitis against the risk of prolonged dialysis when considering transplantation in a child during the pandemic.

Biliary and duodenal complications after « en bloc¼ liver-small bowel transplantation in children. A single center cohort study.

BACKGROUND: The technique of « en bloc¼ liver and small bowel transplantation (L-BT) spares a biliary anastomosis, but does not protect against biliary complications. We analyze biliary and duodenal complications (BDC) in our pediatric series. METHODS: Between 1994 and 2020, 54 L-BT were performed in 53 children. The procurement technique included in situ vascular dissection and pancreatic reduction to the head until 2009 (group A). Thereafter, the whole pancreas was recovered (group B). RESULTS: Nine BDCs occurred in 8/53 (15%) patients (7 in group A and 1 in group B): leak of the donor's duodenal stump (2), stenosis of the extra-pancreatic bile duct (5), and intra-pancreatic bile duct stenosis (2). Median delay for diagnosis of stricture was 8 months (4-168). Interventional radiology was successful in one child only, the others required reoperations. Two patients died, of biliary cirrhosis or cholangitis, 15-month and 12-year post-L-BT. One was listed and liver re-transplanted 13 years post-L-BT. At last follow-up, two patients only had normal liver tests and ultrasound. CONCLUSION: BDC after L-BT can cause severe morbidities. Pancreatic reduction might increase this risk. Early surgical complications or chronic pancreatic rejection might be co-factors. Early diagnosis and treatment are key to the long-term prognosis.

Peritoneovenous Shunt for Intractable Ascites in Children: A Series of 4 Cases.

ABSTRACT: Intractable ascites is a rare condition in children mainly caused by cirrhosis or lymphatic disorders. Internal drainage may be considered as rescue therapy. In our department, 4 patients ages from 2 months to 15 years old underwent a peritoneovenous shunt (PVS) placement between 2010 and 2020. The surgically inserted device was a pumping device that enabled to drain ascites from the peritoneum into the venous system via the internal jugular vein (Denver shunt, BD Company, NJ). Immediate efficient drainage was achieved in all cases and lasted up to 9 years. Two major complications occurred: a postoperative fat embolism requiring urgent temporary ligation of the shunt and endocarditis shortly after inguinal hernia repair performed 16 months after placement of the shunt. Implementation of a PVS may be a useful procedure in patients with refractory ascites. Chylous ascites should be drained and washed totally before activating the device to avoid fat embolism. Antibiotic prophylaxis is required when abdominal surgery is planned while the device is in place.

Quality of life in long term survivors of pediatric intestinal transplantation compared with liver transplantation and home parenteral nutrition: A prospective single-center pilot study.

Health-related quality of life (HRQOL) after intestinal transplantation (IT) is important, as many psychological troubles have been reported in these patients on the long term. Our aim was to assess and compare HRQOL of patients after IT to patients after liver transplantation (LT) or on home parenteral nutrition (HPN) for intestinal failure. A cross-sectional study included patients and their parents between 10 and 18 years of age, on HPN for more than 2 years, or who underwent IT or LT, with a graft survival longer than 2 years. Quality of life was explored by Child Health Questionnaire. Thirteen children-parents dyads after IT, 10 after LT, and eight children on HPN completed the survey. Patients were a median age of 14 years old, a median of 10 years post-transplantation or on HPN. Patients after IT scored lower than patients after LT or on HPN in "social limitations due to behavioral difficulties" and in "behavior." They scored higher than those on HPN in "global health." Parents of children after IT scored lower than those after LT in many domains. No relevant correlation with clinical data was found. Our study showed the multi-level impact of IT on quality of life of patients and their parents. It highlights the importance of a regular psychological follow-up for patients, but also of a psychological support for families. Helping the patients to overcome the difficulties at adolescence may improve their mental health in adulthood.

Long-term kidney and liver outcome in 50 children with autosomal recessive polycystic kidney disease.

BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) is a rare ciliopathy characterized by congenital hepatic fibrosis and cystic kidney disease. Lack of data about long-term follow-up makes it difficult to discuss timing and type of organ transplantation. Our objectives were to evaluate long-term evolution and indications for transplantation, from birth to adulthood. METHODS: Neonatal survivors and patients diagnosed in postnatal period with ARPKD between 1985 January and 2017 December from 3 French pediatric centers were retrospectively enrolled in the study. RESULTS: Fifty patients with mean follow-up 12.5 ± 1 years were enrolled. ARPKD was diagnosed before birth in 24%, and at mean age 1.8 years in others. Thirty-three patients were < 1 year of age at first symptoms, which were mostly kidney-related. These most often presented high blood pressure during follow-up. Portal hypertension was diagnosed in 29 patients (58%), 4 of them with bleeding from esophageal varices. Eight patients presented cholangitis (> 3 episodes in three children). Liver function was normal in all patients. Nine children received a kidney transplant without liver complications. A 20-year-old patient received a combined liver-kidney transplant (CLKT) for recurrent cholangitis, and a 15-year-old boy an isolated liver transplant for uncontrollable variceal bleeding despite portosystemic shunt. CONCLUSIONS: Long-term outcome in patients with ARPKD is heterogeneous, and in this cohort did not depend on age at diagnosis except for blood pressure. Few patients required liver transplantation. Indications for liver or combined liver-kidney transplantation were limited to recurrent cholangitis or uncontrollable portal hypertension. Liver complications after kidney transplantation were not significant.

Therapeutic plasma exchange for life-threatening pediatric disorders.

INTRODUCTION: Therapeutic plasma exchange (TPE) is acknowledged to be an effective treatment in life-threatening pediatric disorders. Apheresis for pediatric diseases has been poorly investigated, and most studies to date featured small numbers of patients and lacked control groups. The objective of the present study was to evaluate the tolerance of TPE in pediatric patients. MATERIALS AND METHODS: A retrospective cohort study via a web-based electronic case report form including pediatric patients referred for TPE between January 2005 and December 2014. RESULTS: A total of 78 patients (median [range] age: 9.8 [0.53-17.93]) and 731 TPE procedures were analyzed. The indications were antibody-mediated rejection (n = 33; 42%) and desensitization therapy (n = 5; 6%) after solid organ or hematopoietic stem cell transplantation, thrombotic microangiopathy (n = 17; 22%), pediatric inflammatory diseases (n = 16; 21%), kidney diseases (n = 6; 8%), and hyperviscosity syndrome (n = 1; 1%). On average, each patient underwent six procedures during the first session [range: 1-19]. In the 2 weeks following the start of a session, 72 patients (92%) presented a total of 311 adverse events (AEs) potentially related to TPE. The risk of AEs was not related to the indication for TPE, the intensity of care, venous access, plasma substitute use, or body weight. None of the deaths was related to the TPE. CONCLUSION: We studied one of the largest retrospective pediatric cohorts described to date. Our experience of TPE children's TPE feasibility concerned specific, life-threatening conditions and otherwise treatment-refractory diseases.

Beyond 10 years, with or without an intestinal graft: Present and future?

Long-term outcomes in children undergoing intestinal transplantation remain unclear. Seventy-one children underwent intestinal transplantation in our center from 1989 to 2007. We report on 10-year posttransplant outcomes with (group 1, n = 26) and without (group 2, n = 9) a functional graft. Ten-year patient and graft survival rates were 53% and 36%, respectively. Most patients were studying or working, one third having psychiatric disorders. All patients in group 1 were weaned off parenteral nutrition with mostly normal physical growth and subnormal energy absorption. Graft histology from 15 late biopsies showed minimal abnormality. However, micronutrient deficiencies and fat malabsorption were frequent; biliary complications occurred in 4 patients among the 17 who underwent liver transplantation; median renal clearance was 87 mL/min/1.73 m2 . Four patients in group 1 experienced late acute rejection. Among the 9 patients in group 2, 4 died after 10 years and 2 developed significant liver fibrosis. Liver transplantation and the use of a 3-drug regimen including sirolimus or mycophenolate mofetil were associated with improved graft survival. Therefore, intestinal transplantation may enable a satisfactory digestive function in the long term. The prognosis of graft removal without retransplantation is better than expected. Regular monitoring of micronutrients, early psychological assessment, and use of sirolimus are recommended.

Long-term outcome of methylmalonic aciduria after kidney, liver, or combined liver-kidney transplantation: The French experience.

Organ transplantation is discussed in methylmalonic aciduria (MMA) for renal failure, and poor quality of life and neurological outcome. We retrospectively evaluated 23 French MMA patients after kidney (KT), liver-kidney (LKT), and liver transplantation (LT). Two patients died, one after LKT, one of hepatoblastoma after KT. One graft was lost early after KT. Of 18 evaluable patients, 12 previously on dialysis, 8 underwent KT (mean 12.5 years), 8 LKT (mean 7 years), and 2 LT (7 and 2.5 years). At a median follow-up of 7.3 (KT), 2.3 (LKT), and 1.0 years (LT), no metabolic decompensation occurred except in 1 KT. Plasma and urine MMA levels dramatically decreased, more after LKT. Protein intake was increased more significantly after LKT than KT. Enteral nutrition was stopped in 7/8 LKT, 1/8 KT. Early complications were frequent after LKT. Neurological disorders occurred in four LKT, reversible in one. Five years after KT, four patients had renal failure. The metabolic outcomes were much better after LKT than KT. LKT in MMA is difficult but improves the quality of life. KT will be rarely indicated. We need more long-term data to indicate early LT, in the hope to delay renal failure and prevent neurodevelopmental complications.

Tumor rupture in hepatoblastoma: A high risk factor?

BACKGROUND: Hepatoblastoma tumor rupture is a high-risk criterion in the SIOPEL 3/4 protocol. Little is known about the outcome of these children. METHODS: Radiological signs of possible tumor rupture, defined as peritoneal effusion, peritoneal nodules, or hepatic subcapsular hematoma, were reported in 24 of 150 patients treated for hepatoblastoma in France from January 2000 to December 2014 after central radiological expert review. RESULTS: Twenty-two patients with available clinical data were included (nine PRETEXT-I/II, six PRETEXT-III, seven PRETEXT-IV, and five had lung metastases). Five patients had a subcapsular hematoma only, and 17 patients had intraperitoneal rupture (subcapsular hematoma and peritoneal effusion). A hepatic biopsy was performed in 19 patients. Intraperitoneal rupture occurred before biopsy in 12 and after biopsy in three (including one with prebiopsy subcapsular hematoma) (missing data: two). All patients were treated with chemotherapy, with high-risk regimens including cisplatin or carboplatin and doxorubicin in 19 and cisplatin or carboplatin alone in three. Liver surgery was performed in 20 patients (including three liver transplants). Fifteen patients (68%) achieved complete remission. With a median follow-up of 5.5 years, 11 events occurred (six progressions and three relapses, including three peritoneal progressions/relapses, one surgical complication, and one second cancer) and eight patients died. One of eight patients with no other high-risk criterion had a relapse. The three-year event-free survival and overall survival rates were 49.6% (95% CI = 30-69) and 68.2% (40-84), respectively. CONCLUSIONS: Tumor rupture is predictive of poor prognosis with risk of peritoneal progression/relapse. However, it should not be a contraindication for liver transplantation.

Management of Biliary Atresia in France 1986 to 2015: Long-term Results.

OBJECTIVES: This study analyses the prognosis of biliary atresia (BA) in France since 1986, when both Kasai operation (KOp) and liver transplantation (LT) became widely available. METHODS: The charts of all patients diagnosed with BA born between 1986 and 2015 and living in France were reviewed. RESULTS: A total of 1428 patients were included; 1340 (94%) underwent KOp. Total clearance of jaundice (total bilirubin ≤20 µmol/L) was documented in 516 patients (39%). Age at KOp (median 59 days, range 6-199) was stable over time. Survival with native liver after KOp was 41%, 35%, 26%, and 22% at 5, 10, 20, and 30 years, stable in the 4 cohorts. 25-year survival with native liver was 38%, 27%, 22%, and 19% in patients operated in the first, second, third month of life or later, respectively (P = 0.0001). Center caseloads had a significant impact on results in the 1986 to 1996 cohort only. 16%, 7%, 7%, and 8% of patients died without LT in the 4 cohorts (P = 0.0001). A total of 753 patients (55%) underwent LT. Patient survival after LT was 79% at 28 years. Five-year patient survival after LT was 76%, 91%, 88%, and 92% in cohorts 1 to 4, respectively (P < 0.0001). Actual BA patient survival (from diagnosis) was 81%. Five-year BA patient survival was 72%, 88%, 87%, and 87% in cohorts 1986 to 1996, 1997 to 2002, 2003 to 2009, and 2010 to 2015, respectively (P < 0.0001). CONCLUSIONS: In France, 87% of patients with BA survive nowadays and 22% reach the age of 30 years without transplantation. Improvement of BA prognosis is mainly due to reduced mortality before LT and better outcomes after LT.

Antibody-mediated rejection in pediatric small bowel transplantation: Capillaritis is a major determinant of C4d positivity in intestinal transplant biopsies.

The diagnostic criteria for antibody-mediated rejection (ABMR) after small bowel transplantation (SBT) are not clearly defined, although the presence of donor-specific antibodies (DSAs) has been reported to be deleterious for graft survival. We aimed to determine the incidence and prognostic value of DSAs and C4d in pediatric SBT and to identify the histopathologic features associated with C4d positivity. We studied all intestinal biopsies (IBx) obtained in the first year posttransplantation (N = 345) in a prospective cohort of 23 children. DSAs and their capacity to fix C1q were identified by using Luminex technology. Eighteen patients (78%) had DSAs, and 9 had the capacity to fix C1q. Seventy-eight IBx (22.6%) were C4d positive. The independent determinants of C4d positivity were capillaritis grades 2 and 3 (odds ratio [OR] 4.02, P = .047 and OR 5.17, P = .003, respectively), mucosal erosion/ulceration (OR 2.8, P = .019), lamina propria inflammation grades 1 and 2/3 (OR 1.95, P = .043 and OR 3.1, P = .016, respectively), and chorion edema (OR 2.16, P = .028). Complement-fixing DSAs and repeated C4d-positive IBx were associated with poor outcome (P = .021 and P = .001, respectively). Our results support that capillaritis should be considered as a feature of ABMR in SBT and identify C1q-fixing DSAs and repeated C4d positivity as potential markers of poor outcome.

Survival of children after liver transplantation for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) in childhood differs from adult HCC because it is often associated with inherited liver disease. It is, however, unclear whether liver transplantation (LT) for HCC in childhood with or without associated inherited disease has a comparable outcome to adult HCC. On the basis of data from the European Liver Transplant Registry (ELTR), we aimed to investigate if there are differences in patient and graft survival after LT for HCC between children and adults and between patients with underlying inherited versus noninherited liver disease, respectively. We included all 175 children who underwent LT for HCC and were enrolled in ELTR between 1985 and 2012. Of these, 38 had an associated inherited liver disease. Adult HCC patients with (n = 79) and without (n = 316, matched by age, sex, and LT date) inherited liver disease served as an adult comparison population. We used multivariable piecewise Cox regression models with shared frailty terms (for LT center) to compare patient and graft survival between the different HCC groups. Survival analyses demonstrated a superior longterm survival of children with inherited liver disease when compared with children with HCC without inherited liver disease (hazard ratio [HR], 0.29; 95% CI, 0.10-0.90; P = 0.03) and adults with HCC with inherited liver disease (HR, 0.27; 95% CI, 0.06-1.25; P = 0.09). There was no survival difference between adults with and without inherited disease (HR, 1.05; 95% CI, 0.66-1.66; P = 0.84). In conclusion, the potential survival advantage of children with an HCC based on inherited disease should be acknowledged when considering transplantation and prioritization for these patients. Further prospective studies accounting for tumor size and extension at LT are necessary to fully interpret our findings. Liver Transplantation 24 246-255 2018 AASLD.