Hepatic Artery Delineation on Ultrasound Volumes Comparing B-Flow and Color Doppler for Postoperative Monitoring of Pediatric Liver Transplants.

(1) Background: Accurate hepatic artery (HA) depiction following pediatric liver transplantation (LT) is essential for graft surveillance but challenging on ultrasound (US). This study assesses if improved HA delineation can be achieved by recording two-dimensional US volumes in Color Doppler (CD) and B-flow technique. (2) Methods: Of 42 consecutive LT, 37 cases were included, and HA delineation was retrospectively rated using a four-point score (0 = HA not detectable, 3 = HA fully detectable, separable from portal vein) within 48 h post-LT (U1) and before discharge (U2). (3) Results: Adding B-flow compared with CD alone showed superior results at neohilar (U1: 2.2 ± 1.0 vs. 1.1 ± 0.8, p < 0.0001; U2: 2.5 ± 0.8 vs. 1.5 ± 0.9, p < 0.0001) and segmental levels (U1: 2.8 ± 0.6 vs. 0.6 ± 0.8, p < 0.0001; U2: 2.8 ± 0.6 vs. 0.7 ± 0.5, p < 0.0001). (4) Conclusions: Standardized US volume recordings combining B-flow and CD can effectively delineate the HA along its vascular course in pediatric LT. The technique should be further evaluated as a standard monitoring instrument to rule out vascular complications after LT.

European Society of Pediatric Radiology survey of perioperative imaging in pediatric liver transplantation: (2) intraoperative imaging.

BACKGROUND: Liver transplantation is the state-of-the-art curative treatment for end-stage liver disease. Imaging is a key element in the detection of intraoperative and postoperative complications. So far, only limited data regarding the best radiological approach to monitor children during liver transplantation is available. OBJECTIVE: To harmonize the imaging of pediatric liver transplantation, the European Society of Pediatric Radiology Abdominal Taskforce initiated a survey addressing the current status of imaging including the pre-, intra- and postoperative phase. This paper reports the responses related to intraoperative imaging. MATERIALS AND METHODS: An online survey, initiated in 2021, asked European centers performing pediatric liver transplantation 48 questions about their imaging approach. In total, 26 centers were contacted, and 22 institutions from 11 countries returned the survey. RESULTS: Intraoperative ultrasound (US) is used by all sites to assess the quality of the vascular anastomosis in order to ensure optimal perfusion of the liver transplant. Vessel depiction is commonly achieved using color Doppler (95.3%). Additional US-based techniques are employed by fewer centers (power angio mode, 28.6%; B-flow, 19%; contrast-enhanced US, 14.3%). Most centers prefer a collaborative approach, with surgeons responsible for probe handling, while radiologists operate the US machine (47.6%). Less commonly, the intraoperative US is performed by the surgeon alone (28.6%) or by the radiologist alone (23.8%). Timing of US, imaging frequency, and documentation practices vary among centers. CONCLUSION: Intraoperative US is consistently utilized across all sites during pediatric liver transplantation. However, considerable variations were observed in terms of the US setup, technique preferences, timing of controls, and documentation practices. These differences provide valuable insights for future optimization and harmonization studies.

European Society of Pediatric Radiology survey of perioperative imaging in pediatric liver transplantation: (3) postoperative imaging.

BACKGROUND: Liver transplantation is the state-of-the-art curative treatment for end-stage liver disease. Imaging is a key element in the detection of postoperative complications. So far, limited data is available regarding the best radiologic approach to monitor children after liver transplantation. OBJECTIVE: To harmonize the imaging of pediatric liver transplantation, the European Society of Pediatric Radiology Abdominal Taskforce initiated a survey addressing the current status of imaging including the pre-, intra-, and postoperative phases. This paper reports the responses related to postoperative imaging. MATERIALS AND METHODS: An online survey, initiated in 2021, asked European centers performing pediatric liver transplantation 48 questions about their imaging approach. In total, 26 centers were contacted, and 22 institutions from 11 countries returned the survey. RESULTS: All sites commence ultrasound (US) monitoring within 24 h after liver transplantation. Monitoring frequency varies across sites, ranging from every 8 h to 72 h in early, and from daily to sporadic use in late postoperative phases. Predefined US protocols are used by 73% of sites. This commonly includes gray scale, color Doppler, and quantitative flow assessment. Alternative flow imaging techniques, contrast-enhanced US, and elastography are applied at 31.8%, 18.2%, and 63.6% of sites, respectively. Computed tomography is performed at 86.4% of sites when clarification is needed. Magnetic resonance imaging is used for selected cases at 36.4% of sites, mainly for assessment of biliary abnormalities or when blood tests are abnormal. CONCLUSION: Diagnostic imaging is extensively used for postoperative surveillance of children after liver transplantation. While US is generally prioritized, substantial differences were noted in US protocol, timing, and monitoring frequency. The study highlights potential areas for future optimization and standardization of imaging, essential for conducting multicenter studies.

European Society of Pediatric Radiology survey of perioperative imaging in pediatric liver transplantation: (1) pre-transplant evaluation.

BACKGROUND: Liver transplantation is the state-of-the-art curative treatment in end-stage liver disease. Imaging is a key element for successful organ-transplantation to assist surgical planning. So far, only limited data regarding the best radiological approach to prepare children for liver transplantation is available. OBJECTIVES: In an attempt to harmonize imaging surrounding pediatric liver transplantation, the European Society of Pediatric Radiology (ESPR) Abdominal Taskforce initiated a survey addressing the current status of imaging including the pre-, intra-, and postoperative phase. This paper reports the responses on preoperative imaging. MATERIAL AND METHODS: An online survey, initiated in 2021, asked European centers performing pediatric liver transplantation 48 questions about their imaging approach. In total, 26 centers were contacted and 22 institutions from 11 countries returned the survey. From 2018 to 2020, the participating centers collectively conducted 1,524 transplantations, with a median of 20 transplantations per center per annum (range, 8-60). RESULTS: Most sites (64%) consider ultrasound their preferred modality to define anatomy and to plan surgery in children before liver transplantation, and additional cross-sectional imaging is only used to answer specific questions (computed tomography [CT], 90.9%; magnetic resonance imaging [MRI], 54.5%). One-third of centers (31.8%) rely primarily on CT for pre-transplant evaluation. Imaging protocols differed substantially regarding applied CT scan ranges, number of contrast phases (range 1-4 phases), and applied MRI techniques. CONCLUSION: Diagnostic imaging is generally used in the work-up of children before liver transplantation. Substantial differences were noted regarding choice of modalities and protocols. We have identified starting points for future optimization and harmonization of the imaging approach to multicenter studies.

Impact of probe-induced abdominal compression on two-dimensional shear wave elastography measurement of split liver transplants in children.

PURPOSE: To evaluate the effect of probe-induced abdominal compression of split liver transplants (SLT) in children on 2D-shear wave elastography (SWE) values. MATERIALS AND METHODS: Data from 11 children (4.7 ±â€Š4.8 years) who had undergone SLT and SWE were evaluated retrospectively. Elastograms were obtained with probes placed in an epigastric, midline position on the abdominal wall, with no and slight compression, using convex and linear transducers. For each identically positioned probe and condition, 12 serial elastograms were obtained and the SLT diameter was measured. Liver stiffness and degree of SLT compression were compared. RESULTS: Slight probe pressure resulted in SLT compression, with a shorter distance between the cutis and the posterior margin of the liver transplant than in the measurement with no pressure (curved array, 5.0 ±â€Š1.1 vs. 5.9 ±â€Š1.3 cm, mean compression 15 %±â€Š8 %; linear array, 4.7 ±â€Š0.9 vs. 5.3 ±â€Š1.0 cm, mean compression 12 %±â€Š8 %; both p < 0.0001). The median liver stiffness was significantly greater with slight pressure than with no pressure (curved transducer, 13.38 ±â€Š3.0 vs. 7.02 ±â€Š1.7 kPa, p < 0.0001; linear transducer, 18.53 ±â€Š7.1 vs. 9.03 ±â€Š1.5 kPa, p = 0.0003). CONCLUSION: Slight abdominal compression can significantly increase SWE values in children with left-lateral SLT. To obtain meaningful results and reduce operator dependency in free-hand examinations, probe pressure must be controlled carefully. KEY POINTS: · Probe-induced compression can increase elastography values in split liver transplants in children. · In free-hand examination, probe pressure must be controlled carefully. · Pressure loading can be determined indirectly by the anteroposterior transplant diameter. CITATION FORMAT: · Groth M, Fischer L, Herden U et al. Impact of probe-induced abdominal compression on two-dimensional shear wave elastography measurement of split liver transplants in children. Fortschr Röntgenstr 2023; 195: 905 - 912.

Long-term outcome after combined or sequential liver and kidney transplantation in children with infantile and juvenile primary hyperoxaluria type 1.

Introduction: Combined or sequential liver and kidney transplantation (CLKT/SLKT) restores kidney function and corrects the underlying metabolic defect in children with end-stage kidney disease in primary hyperoxaluria type 1 (PH1). However, data on long-term outcome, especially in children with infantile PH1, are rare. Methods: All pediatric PH1-patients who underwent CLKT/SLKT at our center were analyzed retrospectively. Results: Eighteen patients (infantile PH1 n = 10, juvenile PH1 n = 8) underwent transplantation (CLKT n = 17, SLKT n = 1) at a median age of 5.4 years (1.5-11.8). Patient survival was 94% after a median follow-up of 9.2 years (6.4-11.0). Liver and kidney survival-rates after 1, 10, and 15 years were 90%, 85%, 85%, and 90%, 75%, 75%, respectively. Age at transplantation was significantly lower in infantile than juvenile PH1 (1.6 years (1.4-2.4) vs. 12.8 years (8.4-14.1), P = 0.003). Median follow-up was 11.0 years (6.8-11.6) in patients with infantile PH1 vs. 6.9 years (5.7-9.9) in juvenile PH1 (P = 0.15). At latest follow-up kidney and/or liver graft loss and/or death showed a tendency to a higher rate in patients with infantile vs. juvenile PH1 (3/10 vs. 1/8, P = 0.59). Discussion: In conclusion, the overall patient survival and long-term transplant outcome of patients after CLKT/SLKT for PH1 is encouraging. However, results in infantile PH1 tended to be less optimal than in patients with juvenile PH1.

Experience with the mTOR Inhibitor Everolimus in Pediatric Liver Graft Recipients.

INTRODUCTION: Immunosuppression after pediatric liver transplantation remains a major challenge. MTOR inhibitors provide a promising therapeutic approach in combination with reduced CNI after transplantation. However, there are still few data regarding their use in children. PATIENTS: We analyzed 37 patients with a median age of 10 years, who received Everolimus for one or more of the following indications: I = chronic graft dysfunction (n = 22); II = progressive renal impairment (n = 5); III = non-tolerable side effects with previous immunosuppressive medication (n = 6); and IV = malignancies (n = 10). The median follow-up time was 36 months. RESULTS: Patient survival was 97%, and graft survival 84%, respectively. Stabilization of graft function was observed in 59% in subgroup 1, with 18.2% ultimately requiring retransplantation. No patient in subgroup IV developed recurrence of his primary tumor or PTLD by the endpoint of the study. Side effects were observed in 67.5% of the study patients, with infections being the most frequent (n = 20; 54.1%). There were no relevant effects on growth and development. CONCLUSION: Everolimus seems to be a treatment option in selected pediatric liver graft recipients for whom other regimens are not suitable. Overall, the efficacy was good and the side effect profile appeared to be acceptable.

Short- and long-term results of liver transplantation according to age at transplant: a single-center experience of 351 children.

Pediatric liver transplantation (PLT) has very good results at experienced transplant centers. However, there is still an ongoing discussion about inferior outcomes, especially in young infants. The aim of this retrospective study was to evaluate outcomes of infants compared to older recipients in a single center over 20 years. We conducted a retrospective study of children who received liver transplants at our center between 1991 and 2011. Only patients without other limiting organ involvement were included and compared according to age. The inclusion criteria were fulfilled by 351 patients (173 vs. 178). The most common indication in both groups was biliary atresia (82.1% vs. 49.4%). The 1-, 5-, and 10-year patient survivals were 93.8%/91.8%/91.1% and 93%/90.8%/90.1%, and the graft survivals were 90.4%/83.5%/79.6% and 89.4%/81.8%/77.5%, respectively. Complications such as postoperative bleeding, biliary complications, or perfusion impairment occurred more often in infants. Leading indications for retransplantation (vascular complications/primary nonfunction) and leading causes of death (sepsis/multiorgan failure) were the same in both groups. Significant predictors for patient loss were decade of transplantation, retransplantation, postoperative bleeding, and infections for infants. Predictors for graft loss were bowel perforation, arterial thrombosis, and age >12 months. Children can have excellent results, independent of age at PLT.

Recurrent acute liver failure in alanyl-tRNA synthetase-1 (AARS1) deficiency.

AARS1 deficiency belongs to the group of disorders affecting aminoacyl-tRNA synthetases. To date, AARS1 deficiency has only been linked to neurologic disorders. We report a 6-year-old girl with microcephaly and developmental delay who presented with repeated episodes of acute liver failure. Whole-exome sequencing revealed compound heterozygosity for two missense variants within the AARS1 gene, p.[Leu298Gln];[Arg751Gly]), whose functional relevance was demonstrated by decreased enzymatic activity in fibroblasts. This is the first report that shows that AARS1 variants may be associated with recurrent acute liver failure.

[Kidney Cysts and Cystic Nephropathies in Children - A Consensus Guideline by 10 German Medical Societies]. / Nierenzysten und zystische Nierenerkrankungen bei Kindern (AWMF S2k-Leitlinie).

This consensus-based guideline was developed by all relevant German pediatric medical societies. Ultrasound is the standard imaging modality for pre- and postnatal kidney cysts and should also exclude extrarenal manifestations in the abdomen and internal genital organs. MRI has selected indications. Suspicion of a cystic kidney disease should prompt consultation of a pediatric nephrologist. Prenatal management must be tailored to very different degrees of disease severity. After renal oligohydramnios, we recommend delivery in a perinatal center. Neonates should not be denied renal replacement therapy solely because of their age. Children with unilateral multicystic dysplastic kidney do not require routine further imaging or nephrectomy, but long-term nephrology follow-up (as do children with uni- or bilateral kidney hypo-/dysplasia with cysts). ARPKD (autosomal recessive polycystic kidney disease), nephronophthisis, Bardet-Biedl syndrome and HNF1B mutations cause relevant extrarenal disease and genetic testing is advisable. Children with tuberous sclerosis complex, tumor predisposition (e. g. von Hippel Lindau syndrome) or high risk of acquired kidney cysts should have regular ultrasounds. Even asymptomatic children of parents with ADPKD (autosomal dominant PKD) should be monitored for hypertension and proteinuria. Presymptomatic diagnostic ultrasound or genetic examination for ADPKD in minors should only be done after thorough counselling. Simple cysts are very rare in children and ADPKD in a parent should be excluded. Complex renal cysts require further investigation.

Infantile Hepatic Hemangioma: Avoiding Unnecessary Invasive Procedures.

Infantile hepatic hemangioma, the most common vascular tumor of the liver in infancy, can occur with acute postnatal liver and congestive heart failure. Nevertheless, its course is often benign, and many children can be diagnosed and treated without surgical intervention. The distinction from malignant diseases is not always easy and it not clear whether invasive procedures for diagnosis and therapy should be performed. Here we report our experiences in our Center for Pediatric Liver Disease and postulate that large studies are needed to avoid unnecessary invasive procedures for these patients in the future.

Impact on the hepatic flow velocity after pediatric combined liver-kidney transplantation compared to isolated pediatric liver transplantation-A matched-pair analysis.

BACKGROUND: Combined liver-kidney transplantation (CLKT) in children is still a rarely performed procedure. Our aim was to analyze the effect of the simultaneous transplantation of the kidney in pediatric CLKT on the liver graft flow velocity, and vascular complications compared to singular liver transplantation (LTX) in children. METHODS: All pediatric CLKT performed at our institution from 1998 to 2016 were matched with singular LTX and retrospectively analyzed. RESULTS: Overall 30 CLKT were performed in 28 children (median age 8 years, range 1-16) and matched with 30 children undergoing singular LTX (median age 7.9 years, range 1-16). No significant differences were found concerning the systolic peak flow velocity of the hepatic artery (HA) or the resistance index (RI). Vascular complications of the hepatic vessels occurred in 16.7% (CLKT) and 6.7% (LTX). The 1-/5- and 10-year patient survival was 93.3%/93.3% and 93.3% (CLKT) and 100%/100% and 92.9% (LTX). 1-/5-and 10-year liver graft survival was 76.7%/73.2% and 73.2% (CLKT) and 84.4%/75.9% and 69.6% (LTX). CONCLUSION: The simultaneous transplantation of the kidney in CLKT had no negative impact on hepatic flow velocity or vascular complications. Frequent Doppler ultrasound examinations, accurate volume management, and avoidance of abdominal pressure might be an explanation for the results and an excellent graft- and patient survival.

Tissue inhibitor of metalloproteinase 1 and AST-to-Platelet Ratio Index as noninvasive biomarkers predict allograft fibrosis after pediatric liver transplantation.

BACKGROUND: Assessing liver fibrosis in patients after liver transplantation is still largely dependent on liver biopsy. Especially in children, noninvasive methods are of utmost importance. We evaluated tissue inhibitor of metalloproteinase 1 (TIMP1) and AST-to-Platelet Ratio Index (APRI) and their potential as serum biomarkers to predict liver allograft fibrosis (LAF) in a pediatric cohort. METHODS: In this retrospective, observational study, we analyzed 91 protocol liver biopsy specimens from 73 children after pediatric liver transplantation (PLT) and compared histological stage of liver fibrosis using LAF Score (LAFSc) and Ishak Score (IshakSc) to TIMP1-serum concentration and APRI using ROC analysis. RESULTS: In our cohort, TIMP1 and APRI reliably predict LAF. Depending on the histological scoring system, cutoff values for TIMP1 were 328 ng/mL (IshakSc ≥ IV) and 351 ng/mL (LAFSc ≥ 5) with AUC of 0.86 and 0.98. The cutoff for APRI was 0.8 with AUC of 0.87 (IshakSc ≥ IV) and 0.94 (LAFSc ≥ 5). Using LAFSc, TIMP1 and APRI showed excellent diagnostic accuracy to detect severe LAF (LAFSc ≥ 5) with PPV of ≥ 90% and NPV of 100%. CONCLUSION: TIMP1 and APRI are accurate biomarkers to predict severe LAF in children. The use of TIMP1 and APRI will not replace but complement liver biopsies after PLT to further improve our understanding of each individual patient.

Oxalate retinopathy is irreversible despite early combined liver-kidney transplantation in primary hyperoxaluria type 1.

In primary hyperoxaluria type 1 (PH1), systemic oxalate deposition (oxalosis) in end-stage renal disease (ESRD) is associated with high morbidity and mortality, particularly in children with infantile oxalosis (IO). Combined liver and kidney transplantation (CLKT) is the only curative treatment option in these patients. After CLKT, systemic oxalosis decreases continuously, although only insufficient data are available regarding oxalate retinopathy (ROx), leading to severe visual impairment. We analyzed long-term follow-up data of ROx in 13 patients undergoing CLKT for PH1 at our center between 1998 and 2018. Age at transplantation was 1.3-14.2 years, including nine patients with IO. We performed visual acuity testing, slit lamp investigation, funduscopy, fundus photography, and spectral-domain optical coherence tomography (SD-OCT) imaging. Severe (grade 2-4) ROx was present in all nine children with IO but not in the four patients developing ESRD in adolescence. A significant negative correlation was found between age at onset of ESRD and grade of ROx (r = -0.66; P < .001). Notably, follow-up assessment after CLKT demonstrated no regression of ROx after a median of 5.3 years (range 0.6-14). The data show that despite early CLKT in IO, ROx is irreversible and the concomitant visual deterioration occurs prior to transplantation.

The Ocular Phenotype in Primary Hyperoxaluria Type 1.

PURPOSE: To investigate ophthalmic features in a large group of patients with primary hyperoxaluria type 1 (PH1) and to determine the relation between ocular involvement and systemic disease severity. DESIGN: Retrospective, cross-sectional, multicenter study of the OxalEurope Registry Network. METHODS: Sixty-eight patients with PH1 were included. Infantile PH1 was diagnosed in 12 patients, and non-infantile PH1 was diagnosed in 56 patients (17 with end-stage renal disease). Ophthalmic examination included best corrected visual acuity (BCVA) testing and multimodal retinal imaging, including fundus photography and optical coherence tomography (OCT). In selected cases, fundus autofluorescence imaging was performed. RESULTS: All eyes (n = 24) of infantile PH1 patients revealed severe retinal alterations and oxalate deposits, including macular crystals and hyperpigmentations (n = 9, 38%), and subretinal fibrosis (n = 15, 63%) with (n = 7, 47%) or without (n = 8; 53%) associated chronic retinal edema. In 9 eyes (38%, all with subretinal fibrosis), BCVA was significantly reduced (<20/50 Snellen equivalent). In contrast, all eyes (n = 112) of patients with non-infantile PH1 had a BCVA in the normal range (median, 20/20). Only 6 patients with non-infantile disease (11%, all with end-stage renal disease) showed mild, likely PH1-related retinal features. These deposits appeared as focal hyperreflective subretinal lesions on OCT imaging and were hyperautofluorescent on autofluorescence images. CONCLUSIONS: Severe ocular alterations occur in infantile cases, whereas mild or no ocular alterations are typical in non-infantile PH1 patients. The natural history of (sub)retinal oxalate deposits, the pathogenesis of subretinal fibrosis, and exact factors influencing the overall severity of ocular disease manifestation remain to be determined.

Alloimmunity and Cholestasis After Liver Transplantation in Children With Progressive Familial Intrahepatic Cholestasis.

OBJECTIVES: Bile salt export pump (BSEP) deficiency is an important reason for chronic cholestasis leading to liver transplantation (LT) in early childhood. The underlying pathology is a dysfunction of BSEP due to various mutations in the ABCB11 gene. Cases of clinical recurrence after LT due to alloantibodies directed against BSEP (antibody-induced BSEP deficiency [AIBD]) have been reported. Most of these patients could be controlled by intensified immunosuppression. METHODS: We here report on 3 children with BSEP-deficiency and end-stage liver disease, which developed AIBD after LT refractory to extensive immunosuppressive and immunomodulatory treatments; retransplantation was necessary in all 3 patients. In 1 patient, a stem cell transplantation was performed successfully. RESULTS: AIBD seems to be induced by triggering factors such as initial impaired graft function or infections after LT. CONCLUSIONS: The underlying mutation may play a role in this process. Intensifying immunosuppression may be able to control AIBD, but some cases seem to be refractory to treatment and require retransplantation. Stem cell transplantation may provide a new therapeutic option for cases refractory to conservative treatment.

Allogeneic haematopoietic stem cell transplantation eliminates alloreactive inhibitory antibodies after liver transplantation for bile salt export pump deficiency.

Progressive familial intrahepatic cholestasis 2 is an autosomal-recessive disorder caused by mutations in the ABCB11 gene, which encodes the bile salt export pump (BSEP). Recurrence of BSEP deficiency after liver transplantation is caused by the development of anti-BSEP antibodies. Antibody-induced BSEP deficiency is typically treated by increasing immunosuppressive therapy. We report, in a child, the first case of allogeneic haematopoietic stem cell transplantation for antibody-induced BSEP deficiency that was refractory to intensive pharmacological immunosuppression and immunoadsorption. After haematopoietic stem cell transplantation, anti-BSEP antibodies were cleared from the patient's serum and later from the canalicular space of the liver graft.

Acute hepatitis as a prequel to very severe aplastic anemia.

Severe aplastic anemia is a rare and potentially life-threatening disease of the bone marrow often requiring allogeneic hematopoietic stem cell transplantation. Pathogenesis of the disease can vary and often remains enigmatic. Occasionally, severe aplastic anemia is associated with prior severe acute hepatitis. Differential diagnosis of acute non-viral hepatitis challenges the physician as pathogenesis remains unclear.We here present a case of a young patient presenting with acute hepatitis followed by severe aplastic anemia successfully treated with allogeneic hematopoietic stem cell transplantation. Due to immunosuppressive treatment with azathioprine for acute hepatitis of putative autoimmune pathogenesis and coincident infection with parvovirus B19, diagnosis of the sequential disease of acute hepatitis followed by severe aplastic anemia was complicated. We discuss the caveats and present a review of the literature.

Targeted Gene Panel Sequencing for Early-onset Inflammatory Bowel Disease and Chronic Diarrhea.

BACKGROUND: In contrast to adult-onset inflammatory bowel disease (IBD), where many genetic loci have been shown to be involved in complex disease etiology, early-onset IBD (eoIBD) and associated syndromes can sometimes present as monogenic conditions. As a result, the clinical phenotype and ideal disease management in these patients often differ from those in adult-onset IBD. However, due to high costs and the complexity of data analysis, high-throughput screening for genetic causes has not yet become a standard part of the diagnostic work-up of eoIBD patients. METHODS: We selected 28 genes of interest associated with monogenic IBD and performed targeted panel sequencing in 71 patients diagnosed with eoIBD or early-onset chronic diarrhea to detect causative variants. We compared these results to whole-exome sequencing (WES) data available for 25 of these patients. RESULTS: Target coverage was significantly higher in the targeted gene panel approach compared with WES, whereas the cost of the panel was considerably lower (approximately 25% of WES). Disease-causing variants affecting protein function were identified in 5 patients (7%), located in genes of the IL10 signaling pathway (3), WAS (1), and DKC1 (1). The functional effects of 8 candidate variants in 5 additional patients (7%) are under further investigation. WES did not identify additional causative mutations in 25 patients. CONCLUSIONS: Targeted gene panel sequencing is a fast and effective screening method for monogenic causes of eoIBD that should be routinely established in national referral centers.