Abstract
Background
In recent years, treatment strategies for ulcerative colitis have evolved with an early step-up approach, the availability of biologicals, and therapeutic drug monitoring.
We ...carried out this study to evaluate the effect of these changes on disease outcomes.
Methods
In this retrospective review, 2 time periods were defined: Group 1 (2005–2010) and Group 2 (2011–2016). Baseline demographic, endoscopic parameters, and medication use were compared. Overall colectomy rate, number of disease flares per year, and number of hospital admissions per year were compared between the 2 groups.
Results
Group 1 had 71 children, and in children in Group 2. The use of 5-ASA increased in Group 2 (Group 2, 99.2% vs. Group 1, 84.5%, P = 0.0007). In addition, infliximab and thiopurines were introduced earlier in the disease course.
The 2-year cumulative probability of colectomy decreased from 14% to 3% (P = 0.02) between the 2 periods. No change in median number of flares per year Group 1, 0.41 (IQR 0.6) vs. Group 2, 0.62 (IQR 0.91), P = 0.28 or median number of hospital admissions per year Group 1, 0.30 (IQR 0.77) vs. Group 2, 0.21 (IQR 0.75), P = 0.52 was seen.
Thereafter, we proceeded to identify the changes in treatment strategies that were responsible for the reduction in colectomy and we found that the use of infliximab OR 3.7 (95% CI 1.1–11.7), P = 0.02, was independently associated with it.
Conclusions
A reduction in 2-year colectomy rates has been observed in patients with pediatric ulcerative colitis since biologics have become available for its treatment. The numbers of disease-flares rates and hospital admissions remain unchanged.
We found that colectomy rates have significantly reduced in pediatric ulcerative colitis since 2012. The cause being multifactorial, with the introduction of biologics an important contributor. However, number of disease flares and hospital admission rates remain unchanged.
Summary
Background
Azathioprine and mercaptopurine are considered safe during pregnancy. However, the pharmacokinetic effects of pregnancy on thiopurine metabolism are undefined.
Aims
To characterise ...thiopurine metabolism in pregnancy and measure infant metabolite levels and outcomes.
Methods
Women with IBD who were taking a thiopurine and pregnant or trying to conceive were recruited. Maternal thiopurine metabolites were measured pre‐conception, in each trimester, at delivery and post‐partum. Infant metabolite levels, full blood examination and liver function testing were performed at birth, and repeated until levels undetectable and haematological and biochemical abnormalities resolved.
Results
Forty patients were included with measurements on at least two occasions, and two with only mother‐baby levels at delivery. The median maternal 6‐TGN level dropped in the second trimester compared with post‐partum (179.0 vs 323.5 pmol/8 × 108 RBCs, P < 0.001) and the median 6‐MMP level increased in the second trimester compared with post‐partum (1103.0 vs 329.5 pmol/8 × 108 RBCs, P < 0.01). At delivery, the median 6‐TGN level was lower in infants (n = 20) than mothers (78.5 vs 217 pmol/8 × 108 RBCs) (P < 0.001). Metabolites were not detected at 6 weeks in any infants. Anaemia was not seen, but thrombocytosis and abnormal liver biochemistry were detected in 80% of infants from 6 weeks, which gradually improved.
Conclusions
6‐TGN levels decrease and 6‐MMP levels increase in the second trimester of pregnancy. Infants are exposed to thiopurine metabolites at low levels with clearance by 6 weeks and no anaemia. The cause of infant thrombocytosis and abnormal liver biochemistry in the absence of metabolites is unclear.
Shunting of maternal thiopurine metabolites in pregnancy
Infants exposed to metabolites with no neonatal anemia
Hepatic and renal dysfunction have been observed in survivors of the Fontan procedure, however their incidence and associated factors remain poorly defined.
A total of 152 participants from a ...Registry of 1528 patients underwent abdominal ultrasound, transient elastography (FibroScan), serum fibrosis score (FibroTest), in vivo Tc-99m DTPA measurement of glomerular filtration rate (mGFR), and urine albumin-creatinine ratio (ACR).
Mean age and time since Fontan were 19.8 ± 9.3 and 14.1 ± 7.6 years, respectively. Features suggestive of hepatic fibrosis were observed on ultrasound in 87/143 (61%) and no patient was diagnosed with hepatocellular carcinoma. FibroScan median kPa was ≥10 in 117/133 (88%), ≥15 in 75/133 (56%), and ≥20 in 41/133 (31%). Fifty-four patients (54/118, 46%) had a FibroTest score ≥0.49 (equivalent to ≥F2 fibrosis). FibroTest score correlated with FibroScan value (r = 0.24, p = 0.015) and ACR (r = 0.29, p = 0.002), and patients with ultrasound features of hepatic fibrosis had a higher FibroScan median kPa (19.5 vs 15.4, p = 0.002). Renal impairment was mild (mGFR 60–89 ml/min/1.73 m2) in 46/131 (35%) and moderate (mGFR 30–59 ml/min/1.73 m2) in 3/131 (2%). Microalbuminuria was detected in 52/139 participants (37%). By multivariable analysis, time since Fontan was associated with increased FibroScan median kPa (β = 0.89, 95% CI 0.54–1.25, p = 0.002) and decreased mGFR (β = −0.77, 95% CI −1.29–0.24, p = 0.005).
In the second decade after Fontan hepatic and renal structure and function are abnormal in a significant number of patients: close to 60% have ultrasonographic evidence of structural hepatic abnormalities, 46% have elevated serum hepatic fibrosis scores, and 57% have either reduced glomerular filtration rate or microalbuminuria. Hepatic and renal function should be monitored for potential impacts on outcomes after Fontan completion.
•In the second decade after the Fontan procedure, abnormalities in hepatic and renal structure and function are common.•Close to two-thirds of patients have ultrasonographic evidence of hepatic fibrosis.•Almost 50% of patients have an elevated serum-based hepatic fibrosis (FibroTest) score.•More than 50% of patients have either a reduced glomerular filtration rate or microalbuminuria.•Hepatic and renal structure and function should be monitored for potential impacts on outcomes after Fontan completion.
Viral hepatitis Hardikar, Winita
Journal of paediatrics and child health,
September 2019, 2019-Sep, 2019-09-00, 20190901, Letnik:
55, Številka:
9
Journal Article
Recenzirano
Hepatitis viruses A to E can cause abnormal liver function tests in children. Although, overall, they are relatively uncommon in children in Australia, epidemiology diagnosis and treatment modalities ...for these viruses have evolved over the last decade. This review provides an update on the diagnosis and treatment of viral hepatitis in children.
The Sialyl Lewis A antigen, or CA 19-9, is the prototype serum biomarker for adenocarcinoma of the pancreas. Despite extensive clinical study of CA 19-9 in gastrointestinal malignancies, surprisingly ...little is known concerning the specific cell types that express this marker during development, tissue regeneration and neoplasia. SOX9 is a transcription factor that plays a key role in these processes in foregut tissues. We report the biochemistry and tissue expression of the GCTM-5 antigen, a pancreatic cancer marker related to, but distinct from, CA19-9. This antigen, defined by two monoclonal antibodies recognising separate epitopes on a large glycoconjugate protein complex, is co-expressed with SOX9 by foregut ductal progenitors in the developing human liver and pancreas, and in pancreatic adenocarcinoma. These progenitors are distinct from cell populations identified by DCLK1, LGR5, or canonical markers of liver and pancreatic progenitor cells. Co-expression of this antigen complex and SOX9 also characterises the ductal metaplasia of submucosal glands that occurs during the development of Barrett's oesophagus. The GCTM-5 antigen complex can be detected in the sera of patients with pancreatic adenocarcinoma. The GCTM-5 epitope shows a much more restricted pattern of expression in the normal adult pancreas relative to CA19-9. Our findings will aid in the identification, characterisation, and monitoring of ductal progenitor cells during development and progression of pancreatic adenocarcinoma in man.
Background and Aim
People with inflammatory bowel disease (IBD) have an increased risk of cardiovascular disease, including in younger adulthood. This may arise in part from chronic, systemic ...low‐grade inflammation. The process of atherosclerosis may begin in childhood. We sought to determine whether pediatric IBD is associated with adverse changes in arterial structure and function as a marker of early increased cardiovascular risk.
Methods
We performed a case–control study comparing children with IBD for a median disease duration of 2.49 (interquartile range 1.23, 4.38) years with healthy children. In a single visit, we collected baseline clinical and anthropometric data, and measured blood pressure, pulse wave velocity, carotid artery distensibility, and aortic and carotid intima‐media thickness. High‐sensitivity C‐reactive protein and fasting lipids were measured.
Results
We enrolled 81 children with IBD (40 with Crohn's disease, 40 with ulcerative colitis, and 1 with unspecified IBD) and 82 control participants. After adjusting for age, sex, body mass index z‐score, blood pressure, and low‐density lipoprotein cholesterol, there was no difference in measures of arterial structure and function in children with IBD compared with controls, nor between those with Crohn's disease or ulcerative colitis.
Conclusion
We did not show any differences in arterial structure and function in children with a history of IBD for less than 5 years compared with healthy controls. IBD diagnosed in childhood may provide a window of opportunity to actively reduce standard cardiovascular risk factors and improve future cardiovascular outcomes.
As adults with inflammatory bowel disease (IBD) have an increased risk of cardiovascular disease, we sought to determine whether children with IBD might have early adverse changes in arterial structure function as a measure of increased cardiovascular risk. This case–control study found that after a mean disease duration of 2.49 years, children with IBD did not have a statistically significant increased risk of having abnormal measures of arterial structure and function.
Homozygous protein C deficiency is an extremely rare condition presenting in the neonatal period with purpura fulminans, with very high rates of morbidity and mortality. Optimal treatment for this ...condition is highly complex, poorly understood, and often limited by cost and product supply. We report a child who presented 2 days after birth with purpura fulminans and severe prenatal eye damage, but no cerebral lesions. He was treated with novel multimodal therapy culminating in liver transplant at 3 years of age. The patient is now 12 years of age, well, with blindness as his only long-term deficit.
Abstract
Contiguous
ABCD1
/
DXS1357E
deletion syndrome (CADDS) is a rare deletion syndrome involving two contiguous genes on Xq28,
ABCD1
and
BCAP31
(formerly known as
DXS1357E
). Only nine ...individuals with this diagnosis have been reported in the medical literature to date. Intragenic loss‐of‐function variants in
BCAP31
cause the deafness, dystonia, and cerebral hypomyelination syndrome (DDCH). Isolated pathogenic intragenic variants in
ABCD1
are associated with the most common peroxisomal disorder, X‐linked adrenoleukodystrophy (X‐ALD), a single transporter deficiency, which in its more severe cerebral form is characterised by childhood‐onset neurodegeneration and high levels of very‐long‐chain fatty acids (VLCFA). While increased VLCFA levels also feature in CADDS, the few patients described to date all presented as neonates with a severe phenotype. Here we report a tenth individual with CADDS, a male infant with dysmorphic facial features who was diagnosed through ultra‐rapid whole genome sequencing (WGS) in the setting of persistent cholestatic liver disease, sensorineural hearing loss, hypotonia and growth failure and developmental delay. Biochemical studies showed elevated VLCFA and mildly reduced plasmalogens. He died at 7 months having developed pancreatic exocrine deficiency and interstitial lung disease, two features we propose to be possible extensions to the CADDS phenotype. We also review the genetic, phenotypic, and biochemical features in previously reported individuals with CADDS.
HCV-specific DAAs have transformed treatment of chronic HCV, but few studies have evaluated these therapies in children.
Patients aged 12–17 years old with chronic GT1 HCV were enrolled into an ...open-label study to receive 12 weeks of LDV/SOF 90 mg/400 mg once daily, and those with HCV GT2 or GT3 to receive SOF (400 mg once daily) + RBV (15 mg/kg/day) for 12 (GT2) or 24 weeks (GT3), respectively. Primary efficacy endpoint was SVR12. Safety was assessed by adverse events and clinical/laboratory data. Pharmacokinetic (PK) sampling was conducted to confirm the appropriateness of the doses.
150 adolescents (100 GT1, 13 GT2 and 37 GT3) were enrolled and treated. The majority were female (56%), white (90%), treatment naive (81%), and vertically infected (80%). The mean age was 15 years (range 12–17). LDV, SOF and GS-331007 (primary metabolite) exposures were within the range of adult exposures observed in the SOF and LDV/SOF phase 2/3 studies. The SVR12 rate was 98% in GT1, 100% in GT2 and 97% in GT3; all 3 patients who were considered not to have achieved SVR12 were lost to follow-up. No adverse event (AE) leading to study drug discontinuation or serious AEs have been reported.
In adolescents, LDV/SOF for 12 weeks and SOF + RBV for 12 or 24 weeks, resulted in a SVR12 rate of 97–100% with no virologic failures. These regimens were well tolerated, demonstrating their potential as an important treatment option for children with HCV infection.
Lathosterolosis is a rare autosomal recessive disorder of cholesterol biosynthesis. It is caused by defects in the SC5D (sterol C5‐desaturase) gene which encodes for the ...3‐beta‐hydroxysteroid‐delta‐5‐desaturase (also called sterol‐C5‐desaturase or lathosterol dehydrogenase). Only six cases have been described in the literature, but it is possible that a number of patients with milder forms of the condition might have been missed. Lathosterolosis manifests as microcephaly, bilateral cataracts, dysmorphism, limb anomalies, and developmental delay/intellectual disability. Liver involvement is variable and can range from normal liver function tests to portal fibrosis and cirrhosis. Diagnosis is made by demonstration of specific mutations in the SC5D gene and by plasma sterol analysis to confirm elevated lathosterol levels. In this report, we describe a girl with transaminitis in association with developmental delay/intellectual disability, facial dysmorphism, limb anomalies, and bilateral cataracts. Fibroscan showed severe liver fibrosis. Plasma sterol analysis and exome sequencing confirmed the diagnosis of lathosterolosis. Simvastatin treatment resulted in lowering of plasma lathosterol levels, improvement in transaminitis, and liver fibrosis grade, suggesting that children with this condition should be actively treated in order to prevent progression of liver disease.
PDF
