A text messaging intervention and quality of life in adolescents with solid organ transplants.

BACKGROUND: Facilitating communication between adolescents and HCP outside of appointments may enhance patient experience and outcomes. The purpose of this study was to determine whether SMS enhances the healthcare experience, QoL, and medication adherence in adolescent SOT patients. METHODS: This was a prospective observational study of an SMS platform (WelTel Inc) for SOT patients aged 12-19 years. QoL was assessed before and after using the PedsQL™ Transplant Module. Medication adherence was assessed with the frequency of therapeutic tacrolimus levels and variation based on control chart analysis. Patient experience and engagement was evaluated with surveys, response rate to messages, and number of clinical conversations (>2 messages). RESULTS: Twenty-three patients were included (median age 15.7 years (IQR 13.6-17.1)). Median intervention duration was 13.5 months (range 4.0-16.7 months). There was a 68% response rate (742/1095) with 375 clinical conversations. The majority of patients reported the intervention provided a positive outlook on their health (17/23), was useful (18/23), and improved their connection to HCPs (17/23). Following the intervention, there was no significant difference in the median scaled QoL scores (pre-intervention: 81 (IQR 76.5-93.3), post-intervention: 78 (IQR 76-93); p = .37), mean percentage of therapeutic tacrolimus levels (pre-intervention: 52 ± 25%, post-intervention: 65 ± 17%; p = .07), or variation on control chart analysis of tacrolimus levels. CONCLUSIONS: The WelTel messaging platform provided supplemental clinical care for a group of adolescent SOT patients that enhanced their healthcare experience. Patient QoL and adherence were unchanged following the intervention and remained at a high level.

Immunologic benefits of maternal living donor allografts in pediatric liver transplantation: fewer rejection episodes and no evidence of de novo allosensitization.

BACKGROUND: Pediatric liver transplant (LT) recipients of maternal living liver donor (LLD) grafts have been reported to experience fewer rejection episodes. However, it is unclear whether this benefit translates to reduction in developing donor-specific antibody (DSA) among maternal-LLD recipients. The aim of this study was to compare immunologic outcomes among maternal-LLD, non-maternal-LLD, and deceased donor liver transplant (DDLT) recipients. METHODS: Children (≤18 years) who underwent LT between 1/1998 and 12/2019 at two high-volume LT centers in North America were evaluated. Patients were divided into three groups by type of graft received (maternal-LLD, non-maternal LLD, and DDLT). Clinical variables and outcomes were compared according to each graft type. RESULTS: A total of 450 pediatric primary LT were analyzed: 275 (61.1%) DDLT, 73 (16.2%) maternal-LLD, and 102 (22.6%) non-maternal-LLD. Children receiving LLD grafts were less likely to develop rejection when compared to the DDLT group (DDLT 46.9% vs. maternal-LLD 31.5% vs. non-maternal-LLD 28.4%, p = 0.001). There was no difference in rejection rates between maternal and non-maternal-LLD recipients. A higher percentage of maternal-LLD recipients were on immunosuppression monotherapy compared to non-maternal-LLD and DDLT recipients (6.7% vs. 1.2 vs. 2.4%, respectively). A subgroup of 68 patients were tested for DSA post-LT. Maternal-LLD recipients were less likely to develop de novo DSA (maternal-LLD 11.8% vs. non-maternal-LLD 19.3% vs. DDLT 43%, p = 0.018). None of the maternal-LLD recipients developed antibody-mediated rejection. CONCLUSIONS: These data support the concept of immunologic benefit of maternal-LLD in pediatric LT, with lower rates of rejection and allosensitization post-LT when compared to DDLT recipients.

Chronic recurrent multifocal osteomyelitis and primary sclerosing cholangitis with type 1 autoimmune hepatitis in a child with ulcerative colitis: a case report.

BACKGROUND: Chronic Recurrent Multifocal Osteomyelitis (CRMO) is a condition characterized by sterile bone inflammation, usually occurring in childhood. Although the etiology remains unclear, this condition has been associated with inflammatory bowel disease (IBD). Primary sclerosing cholangitis (PSC) and Autoimmune Hepatitis (AIH) are also uncommon pediatric conditions with a known association with IBD. CASE PRESENTATION: We present a unique case of a pediatric patient with an initial diagnosis of CRMO, with subsequent diagnosis of autoimmune hepatitis and PSC overlap, and eventually IBD. CONCLUSIONS: Patients with CRMO may also develop PSC in addition to IBD, further highlighting the importance of IBD pathophysiology in both conditions. Clinical screening of associated gastrointestinal findings may be of value in patients with CRMO.

Single Topic Conference on Autoimmune Liver Disease from the Canadian Association for the Study of the Liver.

Autoimmune liver disease (AILD) spans a spectrum of chronic disorders affecting the liver parenchyma and biliary system. Three main categories of AILD are autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC). This review condenses the presentation and discussions of the Single Topic Conference (STC) on AILD that was held in Ottawa, Ontario, in November 2019. We cover generalities regarding disease presentation and clinical diagnosis; mechanistic themes; treatment paradigms; clinical trials, including approaches and challenges to new therapies; and looking beyond traditional disease boundaries. Although these diseases are considered autoimmune, the etiology and role of environmental triggers are poorly understood. AILDs are progressive and chronic conditions that affect survival and quality of life. Advances have been made in PBC treatment because second-line treatments are now available (obeticholic acid, bezafibrate); however, a significant proportion still present suboptimal response. AIH treatment has remained unchanged for several decades, and data suggest that fewer than 50% of patients achieve a complete response and as many as 80% develop treatment-related side effects. B-cell depletion therapy to treat AIH is in an early stage of development and has shown promising results. An effective treatment for PSC is urgently needed. Liver transplant remains the best option for patients who develop decompensated cirrhosis or hepatocellular carcinoma within specific criteria, but recurrent AILD might occur. Continued efforts are warranted to develop networks for AILD aimed at assessing geo-epidemiological, clinical, and biochemical differences to capture the new treatment era in Canada.

Role of transient elastography and APRI in the assessment of pediatric cystic fibrosis liver disease.

Background: Diagnosis and monitoring of cystic fibrosis liver disease (CFLD) is challenging. Transient elastography (TE) is a rapid, non-invasive method for assessing liver fibrosis. Its role in detecting fibrosis in CFLD has only begun to be explored. The aspartate aminotransferase to platelet ratio index (APRI) has been validated as a predictor of hepatic fibrosis in other chronic liver diseases. The purpose of this study was to assess the utility of APRI and TE in identifying liver fibrosis in pediatric CF patients. Methods: Patients aged 2-18 years were recruited from the British Columbia Children's Hospital CF clinic. Patients were determined to have CFLD using standard criteria. Charts were reviewed, and each patient underwent TE. Results: Of the 55 patients included in the study (50.9% male, mean age 11.6 y), 22 (40%) had CFLD. All mean liver enzymes were higher in the CFLD group, notably alanine transaminase (p = 0.031). Mean liver stiffness (LS) and APRI were also higher in the CFLD group (LS: 5.9 versus 4.5 kPa, p = 0.015; APRI: 0.40 versus 0.32, p = 0.119). Linear regression showed a mild positive association between the two (r 2 = 0.386). Conclusions: TE values were higher among CFLD patients and correlated with APRI values, suggesting that these tools may have clinical applications for identifying and following this population. Further research is needed on a larger scale to determine the relative value and clinical utility of TE and APRI among patients with CFLD.

Fontan-Associated Liver Disease: Spectrum of Disease in Children and Adolescents.

Background Information is evolving on liver disease in pediatric patients with Fontan physiology. The purpose of this investigation is to evaluate the spectrum of liver disease in a pediatric population of patients with Fontan physiology and evaluate transient elastography (TE) as a noninvasive marker of liver disease. Methods and Results We prospectively enrolled all children with Fontan physiology. All patients underwent comprehensive liver evaluation including liver enzymes (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase), aspartate transaminase to platelet ratio index, albumin, bilirubin, international normalized ratio, complete blood cell count, abdominal ultrasound, and TE. Transjugular liver biopsies and hemodynamic measurements were performed in a subset of patients. A total of 76 children (median, 11.7; interquartile range, 8.4-14.8 [56% male]) were evaluated, with 17 having a transjugular liver biopsy (median 14.8 years; interquartile range, 14.3-17.4). All biopsies showed pathological changes. The severity of liver pathology did not correlate with TE. There was a positive correlation between TE and time since Fontan (R=0.42, P<0.01), aspartate transaminase to platelet ratio index (R=0.29, P=0.02), aspartate transaminase (R=-0.42, P<0.01), and platelets (R=-0.42, P<0.01). Splenomegaly on abdominal ultrasound was correlated with TE (z=-2.2, P=0.03), low platelet count (z=1.9, P=0.05), low aspartate transaminase (z=1.9, P=0.02), and low alkaline phosphatase (z=2.4, P=0.02). Conclusions Liver disease was ubiquitous in our cohort of pediatric patients with Fontan Physiology. Given the correlation between TE and time from Fontan, TE shows potential as a prospective marker of liver pathology. However, individual measurements with TE do not correlate with the severity of pathology. Given the prevalence of liver disease in this population, protective measures of liver health as well as routine liver health surveillance should be implemented with consideration for hepatology consultation and biopsy in the event of abnormal liver biochemical markers or imaging.

Clinical Characteristics and Complications of Pediatric Liver Biopsy: A Single Centre Experience.

INTRODUCTION: Percutaneous liver biopsy (LB) is the gold standard method for evaluation and management of patients with liver disease. The purpose of this study was to characterize pediatric patients undergoing LB at British Columbia Children's Hospital, and to determine the rate and timing of complications following the procedure. MATERIAL AND METHODS: The medical records of all pediatric patients who underwent LB during a six-year retrospective study were reviewed to collect demographic and procedure-related data. RESULTS: 223 LBs were performed, and 179 of these biopsies were percutaneous or transjugular. Elevated liver enzymes and cholestasis together accounted for almost 70% of the indications for LB, and the histological analysis of liver tissue yielded a specific diagnosis in 89 % of the cases. There were no deaths and no major complications related to LB. The most frequent minor complication was pain (59% of LBs) and the other complications were bleeding-related and classified as minor. The vast majority of complications (88%) were recognized within 8 h of the LB. CONCLUSIONS: LB is a valuable and safe procedure in pediatric patients with a low rate of complications. Pediatric patients can be discharged home safely should no complications occur within the first 8-12 h after the procedure.

Assessment of Liver Stiffness in Pediatric Fontan Patients Using Transient Elastography.

Background. Hepatic fibrosis is a potential complication following Fontan surgery and heralds long-term risk for cirrhosis. Transient elastography (TE) is a rapid, noninvasive method to assess liver fibrosis by measuring liver stiffness. Objectives. To compare liver stiffness and liver biochemistries in pediatric Fontan patients with age- and sex-matched controls and to determine patients' acceptance of TE. Methods. Patients were recruited from British Columbia Children's Hospital. Twenty-two Fontan patients (15 males) were identified. Demographic information and cardiac data were collected. TE was measured using size-appropriate probes. Results. The median age of the Fontan cohort was 13.7 (5.9-16.8) years. Time from Fontan surgery to TE was 9.6 (1.0-12.9) years. The median Fontan circuit pressure was 13 (11-14) mmHg. TE values were higher in Fontan patients versus controls (18.6 versus 4.7 kPa, p < 0.001). There was no association between TE values and patient age (r = 0.41, p = 0.058), time since Fontan surgery (r = 0.40, p = 0.062), or median Fontan circuit pressure (CVP) (r = 0.35, p = 0.111). Patients found TE to be nonpainful, convenient, and safe. Conclusions. TE is feasible to assess liver stiffness in children following Fontan surgery. Pediatric Fontan patients have markedly elevated liver stiffness values. TE may have important utility in liver care follow-up of pediatric Fontan patients.

Incidence and Characteristics of Autoimmune Hepatitis.

BACKGROUND AND OBJECTIVES: Autoimmune hepatitis (AIH) is a progressive inflammatory liver disease of unknown etiology, with limited population-based estimates of pediatric incidence. We reported the incidence of pediatric AIH in Canada and described its clinical characteristics. METHODS: We conducted a retrospective cohort study of patients aged <18 years diagnosed with AIH between 2000-2009 at all pediatric centers in Canada. RESULTS: A total of 159 children with AIH (60.3% female, 13.2% type 2 AIH) were identified. Annual incidence was 0.23 per 100000 children. Median age at presentation for type 1 was 12 years (interquartile range: 11-14) versus 10 years for type 2 (interquartile range: 4.5-13) (P = .03). Fatigue (58%), jaundice (54%), and abdominal pain (49%) were the most common presenting symptoms. Serum albumin (33 vs 38 g/L; P = .03) and platelet count (187 000 vs 249 000; P <.001) were significantly lower and the international normalized ratio (1.4 vs 1.2; P <.001) was higher in cirrhotic versus noncirrhotic patients. Initial treatment included corticosteroids (80%), azathioprine (32%), and/or cyclosporine (13%). Response to treatment at 1 year was complete in 90%, and partial in 3%. 3% of patients had no response, and 3% responded and later relapsed. Nine patients underwent liver transplantation, and 4 patients died at a mean follow-up of 4 years. CONCLUSIONS: AIH is uncommon in children and adolescents in Canada. Type 1 AIH was diagnosed 5.5 times more frequently than type 2 AIH. Most patients respond well to conventional therapy, diminishing the need for liver transplantation.

Drug reaction with eosinophilia and systemic symptoms syndrome associated with antituberculosis medications.

Drug reaction with eosinophilia and systemic symptoms is a potentially life-threatening syndrome of medication hypersensitivity associated with a wide variety of triggers. Diagnosis can be challenging, as clinical features suggest other conditions. We describe a 12-year-old boy with typical drug reaction with eosinophilia and systemic symptoms syndrome after antituberculosis therapy.

Biliary atresia and survival into adulthood without transplantation: a collaborative multicentre clinic review.

BACKGROUND: Biliary atresia is a progressive biliary injury which occurs only in infants. AIMS: To review the experience of patients surviving into adulthood without the need for liver transplantation in childhood. METHODS: A multicentre review of patients with biliary atresia treated surgically who survived into adulthood without the need for transplantation. RESULTS: Twenty-two patients were identified across four centres. Median age at the last follow-up was 25 years (range: 18-46), and 21 patients had clinical features of portal hypertension. At last follow-up values of liver enzymes varied from normal to 15 × the upper limit of normal (ULN) for ALT (median 2.11 × ULN) and 9 × the ULN for ALP (median 2.02 × ULN). Six patients had a serum bilirubin > 50 µmol/l. Pruritus and jaundice were noted in 8 of 20 patients (40%) and 11 of 22 patients (50%) respectively. Thirteen patients (59.1%) were shown to have imaging features of sclerosing cholangitis, with strictures of intrahepatic bile duct(s) (IHBD), dilatation of IHBD (n = 8), or stone(s) within the IHBD (n = 5). A history of presumed bacterial cholangitis was present in 11 patients (50%). Successful pregnancies were recorded in three of fourteen female patients. Four patients underwent transplant between the ages of 20-27 years. Twenty-one patients (95.5%) were alive, including 18 (81.8%) with their native liver at the time of last follow-up. CONCLUSIONS: Some patients treated for biliary atresia will survive into adulthood with their native liver, but commonly with secondary biliary disease including cholangitis and portal hypertension.

Celiac disease and cardiomyopathy in an adolescent with occult cirrhosis.

Patients with celiac disease commonly present with gastrointestinal symptoms including abdominal pain, bloating, constipation or diarrhea. Extraintestinal manifestations of this small bowel disease are increasingly recognized, and greater numbers of patients are being diagnosed after presenting solely with nongastrointestinal symptoms. The present report describes a case involving a 16-year-old girl with oligomenorrhea who was found to have celiac disease and liver cirrhosis of unknown etiology. Subsequent evaluation revealed cardiac dysfunction consistent with cirrhotic cardiomyopathy, a rare finding in the paediatric population. This patient's unusual presentation permits an exploration of several conditions uncommonly reported in conjunction with celiac disease.

Les patients ayant une maladie cœliaque ont souvent des symptômes gastro-intestinaux, y compris des maux de ventre, des ballonnements, de la constipation ou de la diarrhée. On relève de plus en plus les manifestations extra-intestinales de cette maladie de l'intestin grêle, et plus de patients sont diagnostiqués après avoir présenté seulement des symptômes non gastro-intestinaux. Dans le présent rapport, les auteurs décrivent le cas d'une adolescente de 16 ans ayant une oligoménorrhée chez qui on a découvert une maladie cœliaque et une cirrhose hépatique d'étiologie inconnue. L'évaluation subséquente a révélé une dysfonction cardiaque évocatrice d'une myocardiopathie cirrhotique, une observation rare au sein de la population pédiatrique. La présentation inhabituelle de cette patiente ouvre la voie à l'exploration de plusieurs pathologies dont on rend rarement compte en présence d'une maladie cœliaque.

Biliary atresia with associated structural malformations in Canadian infants.

BACKGROUND: Biliary atresia (BA) is associated with extrahepatic congenital malformations in a minority of affected infants. The term commonly applied to this subgroup is 'BASM' for biliary atresia splenic malformation syndrome, as spleen abnormalities are prominent. AIMS AND METHODS: To examine clinical outcome in Canadian BA patients with extrahepatic congenital malformations in the Canada-wide BA database of patients born between 1985 and 2002, and additionally, to recharacterized the syndrome. Patients had ≥1 of the following: a/polysplenia, abnormal abdominal situs, intestinal malrotation, abdominal vascular anomaly or congenital heart disease. RESULTS: Among 328 BA patients, 44 (13%) had associated congenital abnormalities. Intra-abdominal anomalies included polysplenia (n=25), abnormal abdominal situs (n=9), intestinal malrotation (n=19), portal vein anomaly (n=12), hepatic artery anomaly (n=3) and inferior vena cava interruption (n=20). Twenty-six patients had cardiac malformations including pulmonary stenosis (n=11), ventricular septal defect (n=10), atrial septal defect (n=7), total anomalous pulmonary venous return (n=3), double outlet right ventricle (n=3), tetralogy of Fallot (n=2), atrioventricular canal (n=2), dextrocardia (n=2), bicuspid aortic valve (n=2), hypoplastic left heart (n=1) and partial anomalous pulmonary venous return (n=1). Age at Kasai operation, performance of liver transplant, overall survival, post-Kasai native liver survival and transplant survival were comparable to isolated BA. Presence of polysplenia or complex cardiac disease did not reduce post-Kasai native liver survival. Three patients had ≥2 typical abnormalities without polysplenia: thus, splenic malformations are not essential to this BA subgroup. Hierarchical cluster analysis demonstrated characteristic abnormalities grouped in a multiplicity of combinations, consistent with a spectrum of defective lateralization. CONCLUSION: We suggest that the acronym 'BASM' be redefined as 'biliary atresia structural malformation'.

Drug-induced esophageal injury with an occult vascular ring.

Drug-induced esophageal injury is an under-recognized clinical problem, and is associated with antibiotic use in more than 50% of cases. The current report describes a teenage girl who presented with symptoms of pill-induced esophagitis following doxycycline use. Subsequent investigations identified a previously undiagnosed vascular ring. Although most patients who experience drug-induced esophageal injury have no underlying anatomical or functional disorder of the esophagus, the condition is more common in areas of esophageal narrowing. The present case illustrates the possibility of an occult esophageal obstruction representing a risk factor for pill esophagitis. The etiologies, mechanisms and management of drug-induced esophageal injury are reviewed, and aspects of vascular rings that are relevant to paediatricians are discussed.

Credentials as cultural capital: the pursuit of higher degrees among academic medical trainees.

BACKGROUND: Growing numbers of postgraduate medical trainees pursue master's or PhD degrees together with professional education. This study explored students' motivation for undertaking these degrees and considered theoretical explanations for the forces shaping this phenomenon. METHOD: Using constructivist grounded theory methods, interviews were conducted with 14 fellows pursuing higher degrees during subspecialty pediatric training. Emergent themes were identified from transcripts using constant comparative analysis. RESULTS: Participants pursued higher degrees to be more competitive for academic jobs and to increase their credibility within their field. Academic medicine was felt to demand ever-increasing credentials to position trainees as a good investment. Clinical practice alone was not believed to earn respect and status in academia. CONCLUSIONS: Through mostly tacit means, students absorb values from their academic training environment, learning to regard credentials, research publications, and grants as forms of capital, and also learning that success and status within academia depend on accumulating such capital.