Treatment strategies for hepatic artery complications after pediatric liver transplantation: A systematic review.

This study aimed to evaluate the effectiveness of different treatments for hepatic artery thrombosis (HAT) and hepatic artery stenosis (HAS) after pediatric liver transplantation. We systematically reviewed studies published since 2000 that investigated the management of HAT and/or HAS after pediatric liver transplantation. Studies with a minimum of 5 patients in one of the treatment methods were included. The primary outcomes were technical success rate and graft and patient survival. The secondary outcomes were hepatic artery patency, complications, and incidence of HAT and HAS. Of 3570 studies, we included 19 studies with 328 patients. The incidence was 6.2% for HAT and 4.1% for HAS. Patients with an early HAT treated with surgical revascularization had a median graft survival of 45.7% (interquartile range, 30.7%-60%) and a patient survival of 61.3% (interquartile range, 58.7%-66.9%) compared with the other treatments (conservative, endovascular revascularization, or retransplantation). As for HAS, endovascular and surgical revascularization groups had a patient survival of 85.7% and 100% (interquartile range, 85%-100%), respectively. Despite various treatment methods, HAT after pediatric liver transplantation remains a significant issue that has profound effects on the patient and graft survival. Current evidence is insufficient to determine the most effective treatment for preventing graft failure.

No need for fasting prior to doppler ultrasound of pediatric liver transplants: A self-controlled study.

BACKGROUND: Children frequently undergo routine Doppler-ultrasound (DUS) after liver transplantation (LT) for which they are fasted, but this may cause hunger and discomfort. OBJECTIVE: To determine if DUS measurements, with focus on the portal vein (PV), are affected by prandial changes, and if this affects distress and feasibility of the DUS. MATERIALS AND METHODS: Children were prospectively included to undergo a pre- and postprandial DUS on the same day at 6 months after LT. Pre- and anastomotic PV peak systolic velocity (PSV), and hepatic artery and hepatic vein DUS measurements were obtained. Pre- and postprandial measurements, and relative postprandial change of PV velocity ratio (VR) compared to PV anastomotic PSV, were compared using paired-sample t-tests and intraclass correlation coefficients (ICC). Obscuration by bowel gas, difficulty of DUS, and impact of fasting were assessed using 5-point rating scales. RESULTS: Twenty-eight children (median age 3.5 years, IQR 1.6-10.8) were included; four were subsequently excluded because they were not fasted (N = 2) or withdrew consent for the second DUS (N = 2). Measurements between pre- and postprandial DUS, and relative postprandial change of VR compared to PV anastomotic PSV, were not significantly different (p > .05). Test consistency was good (ICC = 0.69, 95% CI = 0.29-0.67) for PV anastomotic PSV, and excellent (95% CI = 0.61-0.93) for PV VR. Obscuration by bowel gas or ease of DUS did not change after eating (p > .05). The majority (16/28, 57.2%) found fasting difficult, and several (13/28, 46.4%) got upset when fasted. CONCLUSION: Children with an LT do not need to be fasted for routine DUS, which may decrease the burden of the examination.

Waitlist mortality of young patients with biliary atresia: Impact of allocation policy and living donor liver transplantation.

Patients with biliary atresia (BA) below 2 years of age in need of a transplantation largely rely on partial grafts from deceased donors (deceased donor liver transplantation [DDLT]) or living donors (living donor liver transplantation [LDLT]). Because of high waitlist mortality in especially young patients with BA, the Eurotransplant Liver Intestine Advisory Committee (ELIAC) has further prioritized patients with BA listed before their second birthday for allocation of a deceased donor liver since 2014. We evaluated whether this Eurotransplant (ET) allocation prioritization changed the waitlist mortality of young patients with BA. We used a pre-post cohort study design with the implementation of the new allocation rule between the two periods. Participants were patients with BA younger than 2 years who were listed for liver transplantation in the ET database between 2001 and 2018. Competing risk analyses were performed to assess waitlist mortality in the first 2 years after listing. We analyzed a total of 1055 patients with BA, of which 882 had been listed in the preimplementation phase (PRE) and 173 in the postimplementation phase (POST). Waitlist mortality decreased from 6.7% in PRE to 2.3% in POST ( p = 0.03). Interestingly, the proportion of young patients with BA undergoing DDLT decreased from 32% to 18% after ET allocation prioritization ( p = 0.001), whereas LDLT increased from 55% to 74% ( p = 0.001). The proportional increase in LDLT decreased the median waitlist duration of transplanted patients from 1.5 months in PRE to 0.85 months in POST ( p = 0.003). Since 2014, waitlist mortality in young patients with BA has strongly decreased in the ET region. Rather than associated with prioritized allocation of deceased donor organs, the decreased waitlist mortality was related to a higher proportion of patients undergoing LDLT.

Doppler-ultrasound reference values after pediatric liver transplantation: a consecutive cohort study.

OBJECTIVES: Doppler ultrasound (DUS) is the main imaging modality to evaluate vascular complications of pediatric liver transplants (LT). The current study aimed to determine reference values and their change over time. METHODS: A consecutive cohort of pediatric patients undergoing an LT were retrospectively included between 2015 and 2020. Timepoints for standardized DUS were intra-operative and postoperative (day 0), days 1-7, months 1 and 3, and years 1 and 2. DUS measurements of the hepatic artery (HA), portal vein (PV), and hepatic vein(s) (HV) were included if there were no complications during 2 years follow-up. Measurements consisted of: peak systolic velocity (PSV) and resistive index (RI) for the HA, PSV for the PV, and venous pulsatility index (VPI) for the HV. Generalized estimating equations were used to analyze change over time. RESULTS: One hundred twelve pediatric patients with 123 LTs were included (median age 3.3 years, interquartile range 0.7-10.1). Ninety-five HAs, 100 PVs, and 115 HVs without complications were included. Reference values for HA PSV and RI, PV PSV, and HV VPI were obtained for all timepoints (4043 included data points in total) and presented using 5th-95th percentiles and threshold values. All reference values changed significantly over time (p = 0.032 to p < 0.001). CONCLUSIONS: DUS reference values of hepatic vessels in children after LT are presented, reference values change over time with specific vessel-dependent patterns. Timepoint-specific reference values improve the interpretation of DUS values and may help to better weigh their clinical significance. KEY POINTS: • Doppler ultrasound reference values of pediatric liver transplantations are not static but change over time. Applying the correct reference values for the specific timepoint may further improve the interpretation of the measurements. • The pattern of change over time of Doppler ultrasound measurements differs between the hepatic vessel and measurement; knowledge of these patterns may help radiologists to better understand normal postoperative hemodynamic changes.

The potential and limitations of intrahepatic cholangiocyte organoids to study inborn errors of metabolism.

Inborn errors of metabolism (IEMs) comprise a diverse group of individually rare monogenic disorders that affect metabolic pathways. Mutations lead to enzymatic deficiency or dysfunction, which results in intermediate metabolite accumulation or deficit leading to disease phenotypes. Currently, treatment options for many IEMs are insufficient. Rarity of individual IEMs hampers therapy development and phenotypic and genetic heterogeneity suggest beneficial effects of personalized approaches. Recently, cultures of patient-own liver-derived intrahepatic cholangiocyte organoids (ICOs) have been established. Since most metabolic genes are expressed in the liver, patient-derived ICOs represent exciting possibilities for in vitro modeling and personalized drug testing for IEMs. However, the exact application range of ICOs remains unclear. To address this, we examined which metabolic pathways can be studied with ICOs and what the potential and limitations of patient-derived ICOs are to model metabolic functions. We present functional assays in patient ICOs with defects in branched-chain amino acid metabolism (methylmalonic acidemia), copper metabolism (Wilson disease), and transporter defects (cystic fibrosis). We discuss the broad range of functional assays that can be applied to ICOs, but also address the limitations of these patient-specific cell models. In doing so, we aim to guide the selection of the appropriate cell model for studies of a specific disease or metabolic process.

Utility of Preoperative Computed Tomography-Based Body Metrics in Relation to Postoperative Complications in Pediatric Liver Transplantation Recipients.

Computed tomography (CT)-derived body metrics such as skeletal muscle index (SMI), psoas muscle index (PMI), and subcutaneous fat area index (ScFI) are measurable components of sarcopenia, frailty, and nutrition. While these body metrics are advocated in adults for predicting postoperative outcomes after liver transplantation (LT), little is known about their value in pediatric populations. This study assessed the relation between preoperative CT-based body metrics and postoperative short-term outcomes in pediatric LT recipients. Patients aged 0-18 years who underwent a primary LT were retrospectively included (n = 101; median age 0.5 years; range 0.2-17.1). SMI, PMI, and ScFI were derived from preoperative axial CT slices. Postoperative outcomes and complications within 90 days were correlated with the CT-based body metrics. To classify postoperative infections, the Clavien-Dindo (CD) classification was used. Subgroup analyses were performed for age groups (<1, 1-10, and >10 years old). An optimal threshold for test performance was defined using Youden's J-statistic and receiver operating characteristic curve as appropriate. ScFI was significantly (P = 0.001) correlated with moderate to severe postoperative infections (CD grade 3-5) in children aged <1 year, with the optimal ScFI threshold being ≤27.1 cm2 /m2 (sensitivity 80.4% and specificity 77.8%). A weak negative correlation between SMI and the total duration of hospital stay (R = -0.3; P = 0.01) and intensive care unit (ICU) stay (R = -0.3; P = 0.01) was observed in children aged <1 year. No other associations between CT-based body metrics and postoperative outcomes were shown. In children aged <1 year with cirrhotic liver disease undergoing LT, preoperative CT-based body metrics were correlated with moderate to severe postoperative infections (ScFI) and with longer duration of hospital and ICU stay (SMI), and thus can be considered important tools for pre-LT risk assessment.

The potential of dietary treatment in patients with glycogen storage disease type IV.

There is paucity of literature on dietary treatment in glycogen storage disease (GSD) type IV and formal guidelines are not available. Traditionally, liver transplantation was considered the only treatment option for GSD IV. In light of the success of dietary treatment for the other hepatic forms of GSD, we have initiated this observational study to assess the outcomes of medical diets, which limit the accumulation of glycogen. Clinical, dietary, laboratory, and imaging data for 15 GSD IV patients from three centres are presented. Medical diets may have the potential to delay or prevent liver transplantation, improve growth and normalize serum aminotransferases. Individual care plans aim to avoid both hyperglycaemia, hypoglycaemia and/or hyperketosis, to minimize glycogen accumulation and catabolism, respectively. Multidisciplinary monitoring includes balancing between traditional markers of metabolic control (ie, growth, liver size, serum aminotransferases, glucose homeostasis, lactate, and ketones), liver function (ie, synthesis, bile flow and detoxification of protein), and symptoms and signs of portal hypertension.

Assessment of hepatic artery anatomy in pediatric liver transplant recipients: MR angiography versus CT angiography.

During LT screening, children undergo CTA to determine hepatic artery anatomy. However, CTA imparts radiation, unlike MRA. The aim was to compare MRA to CTA in assessing hepatic artery anatomy in pediatric LT recipients. Twenty-one children (median age 8.9 years) who underwent both CTA and fl3D-ce MRA before LT were retrospectively included. Interreader variability between 2 radiologists, image quality, movement artifacts, and confidence scores, were used to compare MRA to CTA. Subgroup analyses for ages <6 years and ≥6 years were performed. Interreader variability for MRA and CTA in children <6 years was comparable (k = 0.839 and k = 0.757, respectively), while in children ≥6 years CTA was superior to MRA (k 1.000 and k 0.000, respectively). Overall image quality and confidence scores of CTA were significantly higher compared to MRA at all ages (2.8/3 vs. 2.3/3, p = .001; and 2.9/3 vs. 2.5/3, p = .003, respectively). Movement artifacts were significantly lower in CTA compared to MRA in children ≥6 years (1.0/3 vs. 1.7/3, p = .010, respectively). CTA is preferred over fl3D-ce MRA for the preoperative assessment of hepatic artery anatomy in children receiving LT, both at ages <6 years and ≥6 years.

Paraneoplastic pemphigus associated with post-transplant lymphoproliferative disorder after small bowel transplantation.

BACKGROUND: PNP is a malignancy-associated autoimmune mucocutaneous syndrome due to autoantibodies against plakins, desmogleins, and other components of the epidermis and basement membrane of epithelial tissues. PNP-causing malignancies comprise mainly lymphoproliferative and hematologic neoplasms. PNP is extremely rare, especially in children. METHODS: Here, we present the first case of a child who developed PNP on a PTLD after small bowel transplantation because of a severe genetic protein-losing enteropathy. RESULTS: The patient in this case report had a severe stomatitis, striate palmoplantar keratoderma, and lichenoid skin lesions. In addition, she had marked esophageal involvement. She had lung pathology due to recurrent pulmonary infections and ventilator injury. Although we found no evidence of BO, she died from severe pneumonia and respiratory failure at the age of 12 years. CONCLUSION: It is exceptional that, despite effective treatment of the PTLD, the girl survived 5 years after her diagnosis of PNP. We hypothesize that the girl survived relatively long after the PNP diagnosis due to strong T-cell suppressive treatments for her small bowel transplantation.

Reversal of secondary protein-losing enteropathy after surgical revision of a jejunal Roux-en-Y loop in a patient after liver transplantation.

Secondary protein-losing enteropathy (PLE) is a rare complication following pediatric liver transplantation (LT), mostly related to venous outflow obstruction of the liver. Here, we discuss a thus far unknown cause of secondary PLE following pediatric LT. A 7-month-old boy underwent LT with biliary anastomosis using a Roux-en-Y jejunal loop. Eleven months later he developed PLE. Routine diagnostic workup was negative. No hepatic outflow obstruction was detected during catheterization. Although the hepatic venous pressure gradient was slightly increased (10 mm Hg), there were no clinical signs of portal hypertension. Albumin scintigraphy with specific early recordings suggested focal albumin intestinal entry in the jejunal Roux-en-Y loop. Local bacterial overgrowth or local lymphangiectasia, possibly due to (venous) congestion, was considered. Treatment with metronidazole did not improve albumin loss. Next, surgical revision of the jejunal Roux-en-Y loop was performed. The explanted loop contained a small abnormal area with a thin hyperemic mucosa, near the former anastomosis. Histopathological analysis showed changes both in the blood vessels and the lymphatic vessels with focal deeper chronic active inflammation resulting in congestion of vessels, hampering lymphatic outflow leading to lymphangiectasia and patchy distortion of lymphatic vessels. Following surgical revision, secondary PLE disappeared, up to now, 1.5 year post revision.

Intestinal Failure and Aberrant Lipid Metabolism in Patients With DGAT1 Deficiency.

BACKGROUND & AIMS: Congenital diarrheal disorders are rare inherited intestinal disorders characterized by intractable, sometimes life-threatening, diarrhea and nutrient malabsorption; some have been associated with mutations in diacylglycerol-acyltransferase 1 (DGAT1), which catalyzes formation of triacylglycerol from diacylglycerol and acyl-CoA. We investigated the mechanisms by which DGAT1 deficiency contributes to intestinal failure using patient-derived organoids. METHODS: We collected blood samples from 10 patients, from 6 unrelated pedigrees, who presented with early-onset severe diarrhea and/or vomiting, hypoalbuminemia, and/or (fatal) protein-losing enteropathy with intestinal failure; we performed next-generation sequencing analysis of DNA from 8 patients. Organoids were generated from duodenal biopsies from 3 patients and 3 healthy individuals (controls). Caco-2 cells and patient-derived dermal fibroblasts were transfected or transduced with vectors that express full-length or mutant forms of DGAT1 or full-length DGAT2. We performed CRISPR/Cas9-guided disruption of DGAT1 in control intestinal organoids. Cells and organoids were analyzed by immunoblot, immunofluorescence, flow cytometry, chromatography, quantitative real-time polymerase chain reaction, and for the activity of caspases 3 and 7. RESULTS: In the 10 patients, we identified 5 bi-allelic loss-of-function mutations in DGAT1. In patient-derived fibroblasts and organoids, the mutations reduced expression of DGAT1 protein and altered triacylglycerol metabolism, resulting in decreased lipid droplet formation after oleic acid addition. Expression of full-length DGAT2 in patient-derived fibroblasts restored formation of lipid droplets. Organoids derived from patients with DGAT1 mutations were more susceptible to lipid-induced cell death than control organoids. CONCLUSIONS: We identified a large cohort of patients with congenital diarrheal disorders with mutations in DGAT1 that reduced expression of its product; dermal fibroblasts and intestinal organoids derived from these patients had altered lipid metabolism and were susceptible to lipid-induced cell death. Expression of full-length wildtype DGAT1 or DGAT2 restored normal lipid metabolism in these cells. These findings indicate the importance of DGAT1 in fat metabolism and lipotoxicity in the intestinal epithelium. A fat-free diet might serve as the first line of therapy for patients with reduced DGAT1 expression. It is important to identify genetic variants associated with congenital diarrheal disorders for proper diagnosis and selection of treatment strategies.

Time-to-reach Target Calprotectin Level in Newly Diagnosed Patients With Inflammatory Bowel Disease.

OBJECTIVES: Treatment targets in inflammatory bowel disease (IBD) move away from controlling symptoms towards complete recovery of the intestinal mucosa. Currently, the most frequently used noninvasive surrogate marker of mucosal healing is a faecal calprotectin concentration in the target range. This study tested if there was a relation between time-to-reach target calprotectin and first flare. METHODS: We prospectively included new-onset IBD patients ages 17 and younger in a cloud-based registry (FastForwardCare) and followed them for at least 52 weeks. They were treated according to Dutch national guidelines that advocate a step-up approach. Time-to-reach target was defined as the first calprotectin measurement below 250 µg/g after the start of induction therapy. Time-to-first flare was the time from the first calprotectin measurement below 250 µg/g until reappearance of symptoms with calprotectin values above 250 µg/g. RESULTS: We included 76 patients (luminal Crohn disease [CD] 43); ulcerative colitis [UC] 33). Median age at diagnosis was, respectively 14.5 and 14.1 years. Median time-to-reach target calprotectin was 37 weeks in CD and 11 weeks in UC patients (Log-rank test, P = 0.001). Once the calprotectin target was reached, time-to-first flare was significantly longer in CD than in UC patients (Log-rank test, P = 0.001). CD patients with time-to-reach target calprotectin ≤12 weeks after conventional induction therapy (ie, exclusive enteral nutrition or steroids) had a more favorable disease course in the first year than those with time-to-reach target calprotectin >12 weeks (Log-rank test, P = 0.057). In UC patients, time-to-reach target calprotectin ≤12 weeks is not associated with a favorable disease course in the first year. CONCLUSIONS: The findings of this prospective registry suggest that a quick response to conventional therapy predicts a favorable disease course in new-onset paediatric CD, but not in UC. The concept "time-to-reach target calprotectin level" rationalizes the indefinite term "response to treatment" and is well suited for studying treatment effectiveness in real-world practices.

Wait-list mortality of young patients with Biliary atresia: Competing risk analysis of a eurotransplant registry-based cohort.

Liver transplantation (LT) is the standard treatment for biliary atresia (BA) patients with end-stage liver disease. The prognosis after LT has steadily improved, but overall prognosis of BA patients is also determined by mortality before LT. We aimed to quantify mortality in young BA patients on the Eurotransplant waiting list and to determine the effect of disease severity and age at time of listing on pretransplant mortality. We used a cohort study design, which incorporated data from the Eurotransplant registry. Participants were 711 BA patients who were below 5 years of age from 5 countries and listed for LT between 2001 and 2014. We applied a competing risk analysis to evaluate simultaneously the outcomes death, LT, and still waiting for a suitable organ. We used Cox proportional hazards regression to assess 2-year mortality. In a subcohort of 416 children, we performed multivariate analyses between 2-year mortality and disease severity or age, each at listing. Disease severity at listing was quantified by the Model for End-Stage Liver Disease (MELD) score, which assesses bilirubin, creatinine, albumin, and international normalized ratio as continuous variables. Two-year wait-list mortality was 7.9%. Age below 6 months and MELD score above 20 points, each at listing, were strongly and independently associated with 2-year mortality (each P < 0.001). A total of 21% of infants who fulfilled both criteria did not survive the first 6 months on the waiting list. In conclusion, our findings quantify mortality among young BA patients on the waiting list and the relative importance of risk factors (age and severity of disease at listing). Our results provide both an evidence base to rationally address high mortality in subgroups and a methodology to assess effects of implemented changes, for example, in allocation rules. Liver Transplantation 24 810-819 2018 AASLD.

Serious complications after button battery ingestion in children.

Serious and fatal complications after button battery ingestion are increasing worldwide. The aim of this study is to describe serious complications after battery ingestion in children in the Netherlands.All pediatric gastroenterologists in the Netherlands performing upper endoscopies were asked to report all serious complications after battery ingestion in children (0-18 years) between 2008 and 2016 retrospectively.Sixteen serious complications were reported: death after massive bleeding through esophageal-aortal fistula (n = 1), esophageal-tracheal fistula (n = 5), stenosis after (suspected) perforation and mediastinitis (n = 5), (suspected) perforation and mediastinitis (n = 3), vocal cord paralysis (n = 1), and required reintubation for dyspnea and stridor (n = 1). The median time interval between ingestion and presentation was 5 (IQR 2-258) h. All children were ≤ 5 (median 1.4; IQR 0.9-2.1) years. Vomiting (31.3%), swallowing/feeding problems (31.3%), and fever (31.3%) were the most common presenting symptoms; however, 18.8% of the patients were asymptomatic (n = 1 missing). All batteries were button batteries (75% ≥ 20 mm; 18.8% < 20 mm; n = 1 missing). The batteries were removed by esophagogastroduodenoscopy (50%) and rigid endoscopy (37.5%) or surgically (12.5%). CONCLUSION: Sixteen serious complications occurred after small and large button batteries ingestion between 2008 and 2016 in both symptomatic and asymptomatic children in the Netherlands. Therefore, immediate intervention after (suspected) button battery ingestion is required. What is Known: • Button battery ingestion may result in serious and fatal complications. • Serious and fatal complications after button battery ingestion are increasing worldwide. What is New: • Sixteen serious complications after button battery ingestion occurred during 2008-2016 in children in the Netherlands. • Serious complications were also caused by small batteries (< 20 mm) in the Netherlands and also occurred in asymptomatic Dutch children.

Increase of Serum γ-Glutamyltransferase Associated With Development of Cirrhotic Cystic Fibrosis Liver Disease.

BACKGROUND: Identification of patients at risk for developing cirrhotic cystic fibrosis liver disease (CCFLD) is essential for targeting potentially preventive treatment. We studied the evolution of serum liver enzymes and thrombocyte counts as predictors of CCFLD development. METHODS: For this study, we defined the diagnosis of CCFLD as the combination of splenomegaly (on either physical examination or ultrasound scan) and macronodularity of the liver on ultrasound scan. We reviewed the medical records of 277 pediatric patients with CF for the diagnosis of CCFLD. In each patient with CCFLD, we reviewed serum liver enzymes and thrombocyte counts in the 2-year period preceding the diagnosis of CCFLD. We compared these results with a non-CCFLD control group (patients with CF older than 15 years with no reported signs or symptoms of CCFLD). RESULTS: In the 2 years preceding the diagnosis, the γ-glutamyltranspeptidase (GGT) levels of patients with CCFLD were significantly higher compared to non-CCFLD controls (42 ±â€Š5 vs 17 ±â€Š2 U/L, respectively; P < 0.001). Corresponding aspartate aminotransferase and alanine aminotransferase levels did not significantly differ between patients with CCFLD and controls. The thrombocyte counts in patients with CCFLD were significantly lower than those in controls (252 ±â€Š108 vs 320 ±â€Š94 × 10 /L, respectively; P < 0.05). The predictive value for CCFLD of a single GGT measurement was low; however, for patients with CF with a mean GGT > 35 U/L, based on repeated measurements, the odds ratio for developing CCFLD was 39 (95% confidence interval 9-175, specificity was 95%, sensitivity was 64%, positive predictive value was 50%). For the thrombocytes, however, no reliable cutoff value could be identified. CONCLUSIONS: In pediatric patients with CF, a persistently high-normal GGT is strongly associated with the diagnosis of CCFLD within 2 years. The prognostic value of a single GGT measurement is limited, but repeated GGT measurements may allow the identification of groups of patients at increased risk for CCFLD.

Incidence, management and outcomes in hepatic artery complications after paediatric liver transplantation: protocol of the retrospective, international, multicentre HEPATIC Registry.

INTRODUCTION: Hepatic artery complications (HACs), such as a thrombosis or stenosis, are serious causes of morbidity and mortality after paediatric liver transplantation (LT). This study will investigate the incidence, current management practices and outcomes in paediatric patients with HAC after LT, including early and late complications. METHODS AND ANALYSIS: The HEPatic Artery stenosis and Thrombosis after liver transplantation In Children (HEPATIC) Registry is an international, retrospective, multicentre, observational study. Any paediatric patient diagnosed with HAC and treated for HAC (at age <18 years) after paediatric LT within a 20-year time period will be included. The primary outcomes are graft and patient survivals. The secondary outcomes are technical success of the intervention, primary and secondary patency after HAC intervention, intraprocedural and postprocedural complications, description of current management practices, and incidence of HAC. ETHICS AND DISSEMINATION: All participating sites will obtain local ethical approval and (waiver of) informed consent following the regulations on the conduct of observational clinical studies. The results will be disseminated through scientific presentations at conferences and through publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: The HEPATIC registry is registered at the ClinicalTrials.gov website; Registry Identifier: NCT05818644.

Abnormal glucose homeostasis and fasting intolerance in patients with congenital porto-systemic shunts.

In physiological glucose homeostasis, the liver plays a crucial role in the extraction of glucose from the portal circulation and storage as glycogen to enable release through glycogenolysis upon fasting. In addition, insulin secreted by the pancreas is partly eliminated from the systemic circulation by hepatic first-pass. Therefore, patients with a congenital porto-systemic shunt present a unique combination of (a) postabsorptive hyperinsulinemic hypoglycaemia (HH) because of decreased insulin elimination and (b) fasting (ketotic) hypoglycaemia because of decreased glycogenolysis. Patients with porto-systemic shunts therefore provide important insight into the role of the portal circulation and hepatic function in different phases of glucose homeostasis.

Effectiveness and safety of catheter-directed thrombolysis in conjunction with percutaneous mechanical thrombectomy for acute iliofemoral deep vein thrombosis: A meta-analysis.

BACKGROUND: Patients with severe acute low iliofemoral deep vein thrombosis (DVT), such as phlegmasia cerulea dolens, benefit from catheter-directed thrombolysis (CDT). This meta-analysis investigated the effectiveness and safety of adjuvant percutaneous mechanical thrombectomy (PMT) during CDT compared with CDT alone in the treatment of acute iliofemoral DVT. METHODS: A meta-analysis was performed in accordance with the PRISMA guidelines. Medline, Embase, the Cochrane Library, China National Knowledge Internet, and Wanfang data were searched for studies on the management of acute iliofemoral DVT by means of CDT or CDT with adjuvant PMT. Randomized, controlled trials and nonrandomized studies were included. The primary outcomes were venous patency rate, major bleeding complications, and post-thrombotic syndrome occurrence within 2 years of the procedure. The secondary outcomes were thrombolytic time and volume, as well as the rates of thigh detumescence and iliac vein stenting. RESULTS: The meta-analysis included 20 eligible studies with a total of 1686 patients. The rates of venous patency (mean difference, 10.11; 95% confidence interval [CI], 5.59-14.62) and thigh detumescence (mean difference, 3.64; 95% CI, 1.10-6.18) of the adjuvant PMT group were higher than those of the CDT alone group. Compared with CDT alone, the adjuvant PMT group experienced fewer incidences of major bleeding complications (odds ratio, 0.45; 95% CI, 0.26-0.77) and occurrences of post-thrombotic syndrome within 2 years of the procedure (odds ratio, 0.55; 95% CI, 0.33-0.92). Furthermore, the duration of thrombolytic therapy was shorter, and the total dose of administered thrombolytics was lower with adjuvant PMT. CONCLUSIONS: Adjuvant PMT during CDT is associated with improved clinical outcomes and a lower incidence of major bleeding complications. The studies investigated were, however, single-center cohort studies, and future randomized controlled trials are needed to substantiate these findings.

Prevalence, management and efficacy of treatment in portal vein obstruction after paediatric liver transplantation: protocol of the retrospective international multicentre PORTAL registry.

INTRODUCTION: Portal vein obstruction (PVO) consists of anastomotic stenosis and thrombosis, which occurs due to a progression of the former. The aim of this large-scale international study is to assess the prevalence, current management practices and efficacy of treatment in patients with PVO. METHODS AND ANALYSIS: The Portal vein Obstruction Revascularisation Therapy After Liver transplantation registry will facilitate an international, retrospective, multicentre, observational study, with 25 centres around the world already actively involved. Paediatric patients (aged <18 years) with a diagnosed PVO between 1 January 2001 and 1 January 2021 after liver transplantation will be eligible for inclusion. The primary endpoints are the prevalence of PVO, primary and secondary patency after PVO intervention and current management practices. Secondary endpoints are patient and graft survival, severe complications of PVO and technical success of revascularisation techniques. ETHICS AND DISSEMINATION: Medical Ethics Review Board of the University Medical Center Groningen has approved the study (METc 2021/072). The results of this study will be disseminated via peer-reviewed publications and scientific presentations at national and international conferences. TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NL9261).