Newborn Screening for Biliary Atresia Schreiber, Richard A
JAMA : the journal of the American Medical Association,
03/2020, Letnik:
323, Številka:
12
Journal Article
Germline JAK1 gain-of-function mutations cause autosomal dominant immune dysregulation and hypereosinophilia with eosinophilic infiltration of the gastrointestinal tract, massive hepatosplenomegaly ...and severe atopic dermatitis that can be successfully treated with ruxolitinib, an oral JAK1/2 inhibitor.
Summary Biliary Atresia and other cholestatic childhood diseases are rare conditions affecting the function and/or anatomy along the canalicular-bile duct continuum, characterised by onset of ...persistent cholestatic jaundice during the neonatal period. Biliary atresia (BA) is the most common among these, but still has an incidence of only 1 in 10–19,000 in Europe and North America. Other diseases such as the genetic conditions, Alagille syndrome (ALGS) and Progressive Familial Intrahepatic Cholestasis (PFIC), are less common. Choledochal malformations are amenable to surgical correction and require a high index of suspicion. The low incidence of such diseases hinder patient-based studies that include large cohorts, while the limited numbers of animal models of disease that recapitulate the spectrum of disease phenotypes hinders both basic research and the development of new treatments. Despite their individual rarity, collectively BA and other cholestatic childhood diseases are the commonest indications for liver transplantation during childhood. Here, we review the recent advances in basic research and clinical progress in these diseases, as well as the research needs. For the various diseases, we formulate current key questions and controversies and identify top priorities to guide future research.
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 (
=0.42,
<0.01), aspartate transaminase to platelet ratio index (
=0.29,
=0.02), aspartate transaminase (
=-0.42,
<0.01), and platelets (
=-0.42,
<0.01). Splenomegaly on abdominal ultrasound was correlated with TE (
=-2.2,
=0.03), low platelet count (
=1.9,
=0.05), low aspartate transaminase (
=1.9,
=0.02), and low alkaline phosphatase (
=2.4,
=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.
Biliary atresia (BA) is a rare newborn liver disease with significant morbidity and mortality, especially if not recognized and treated early in life. It is the most common cause of liver-related ...death in children and the leading indication for liver transplantation in the pediatric population. Timely intervention with a Kasai portoenterostomy (KPE) can significantly improve prognosis. Delayed disease recognition, late patient referral, and untimely surgery remains a worldwide problem. This article will focus on biliary atresia from a global public health perspective, including disease epidemiology, current national screening programs, and their impact on outcome, as well as new and novel BA screening initiatives. Policy challenges for the implementation of BA screening programs will also be discussed, highlighting examples from the North American, European, and Asian experience.
Biliary atresia (BA), a rare newborn liver disease, is the leading cause of liver-related death in children. Early disease recognition and timely surgical Kasai hepatoportoenterostomy (KP) offers ...long-term survival without liver transplant. Universal BA screening in Taiwan using infant stool color cards (ISCCs) has proven effectiveness. We report our experience with infant stool color card (ISCC) BA screening in a province-wide program in British Columbia (BC). The objective of this study is to assess program performance and cost from launch April 1, 2014 to March 31, 2016.
ISCCs distributed to families upon maternity ward discharge. Parents were instructed to monitor their infant's stool color for 1 month and contacted the screening center with concerns. The number of live births, ISCC distribution, BA cases, and costs were recorded. Cases with Program screen success had both acholic stool recognition (ISCC screen success) and timely referral for BA.
All 126 maternity units received ISCCs. Of 87,583 live births there were 6 BA cases. Of the 5 cases with ISCC Screen Success 3 had Program Screen Success. The median KP age in the program screen success and failure groups was 49 (42-52) and 116 (49-184) days, respectively. Program sensitivity was 50%, specificity 99%, positive predictive value 4%, and negative predictive value 99%. A random sample of 1054 charts at BC Children's Hospital found an ISCC distribution rate of 94%. After a phase-in period, the annual program cost was $30,033.82, and the ISCC cost per birth was $0.68.
The screening program has high specificity and distribution with low cost. Successful program case identification had earlier age at KP. Program modifications aim to improve sensitivity. Longer-term studies will determine program impact on health outcomes.
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.
We conducted a retrospective cohort study of patients aged <18 years diagnosed with AIH between 2000-2009 at all pediatric centers in Canada.
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.
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.
Objective
Biliary atresia, a rare newborn liver disease, is the most common cause of liver-related death in children and the main indication for paediatric liver transplantation. Early detection and ...surgical intervention with a Kasai portoenterostomy offers the best chance for long-term patient survival. We conducted a cost-effectiveness analysis to compare no universal screening with screening using either a home-based infant stool colour card with passive card distribution strategy, or conjugated bilirubin testing.
Methods
A Markov model was developed, with structure, costs, and probabilities informed by the literature and clinical expert opinion, to simulate a newborn cohort over a 10-year time horizon. Health benefits were expressed as life-years gained. This analysis was conducted from the perspective of the Canadian publicly funded health care system (all costs in Canadian dollars). Both deterministic and probabilistic analyses were conducted.
Results
Screening using a home-based colour card with passive card distribution was a cost-effective option. For a population of 392,902 annual births in Canada, this strategy cost approximately $192,000 more than no universal screening but led to eight life-years gained (incremental cost-effectiveness ratio (ICER) = $24,065 per life-year gained). Screening using conjugated bilirubin testing versus the colour card cost $2,369,199 more and led to five more life-years gained (ICER= $473,840 per life year gained), and so was not cost-effective.
Conclusions
A home-based screening program using infant stool colour cards with a passive distribution strategy could be highly cost-effective when administered at a low unit cost and with a reasonable screening performance.
Living with end‐stage organ failure is associated with an accumulation of traumatic medical events, and despite recovery after solid‐organ transplantation (SOT), many children continue to exhibit ...lower quality of life (QOL). Few studies have examined the relationship between post‐traumatic stress disorder (PTSD) and QOL among pediatric SOT recipients. We conducted a retrospective, cross‐sectional review of 61 pediatric SOT recipients (12 heart, 30 kidney, and 19 liver) to evaluate the association of PTSD with self‐reported QOL. PTSD was measured by the Child Trauma Screening Questionnaire (CTSQ), and QOL was measured using the PedsQL and PedsQL Transplant Module (PedsQL‐TM) surveys. Demographics, baseline, and contemporaneous factors were tested for independent association. SOT recipients were 15.2 (12.1–17.6) years old at survey completion. Median CTSQ score was 2 (1–3), highest in kidney recipients, and 13% were identified as high risk for PTSD. Median PedsQL score was 83 (70–91) and significantly associated with the CTSQ score (r = −.68, p < .001). Median PedsQL Transplant Module score was 89 (83–95) and similarly associated with the CTSQ score (r = −.64, p < .001). Age at time of surveys and presence of any disability were also independently associated with PedsQL and PedsQL‐TM, respectively. When adjusted for Emotional Functioning, CTSQ remained associated with PedsQL subscores (r = −.65, p < .001). Trauma symptoms are a major modifiable risk factor for lower self‐perceived QOL and represent a potentially important target for post‐transplant rehabilitation. Additional research is needed to understand the root contributors to PTSD and potential treatments in this population.
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