To describe the prevalence and the relationship between asthma, eczema, food allergy, and rhinitis in children after liver transplantation.
Children who were liver transplant recipients were ...investigated to assess whether the high prevalence of food allergies was accompanied by eczema, rhinitis, and asthma. Furthermore, we included 56 children with chronic liver disease to explore the risk of allergy, eczema, and asthma in this group.
After liver transplantation, children had higher prevalence of allergic reactions to food as compared with children with chronic liver disease (P < .001). Current asthma (P = .04) and eczema (P < .02) were observed more frequently in transplanted children as compared with children with chronic liver disease. For transplanted children who had ever received tacrolimus the relative risk (RR) of asthma was 1.7 (95% CI, 1.2-2.4; P = .02) as compared with children with chronic liver disease. Transplanted children with asthma had higher rates of sensitization to food allergens than those without asthma (RR, 3.6; 95% CI, 1.3-10.3; P = .01). The most frequent food allergens associated with asthma in transplanted children were milk (RR for asthma, 3.9; 95% CI, 1.6-9.4; P < .01), eggs (RR, 2.9; 95% CI, 1.2-7.0; P = .03), and peanuts (RR, 3.7; 95% CI, 1.6-8.3; P < .01). Food allergies occurred earlier than asthma, at 1.5 years after transplantation (IQR, 0.5-3.0 years) vs 2.5 years after transplantation (IQR, 1.0-4.5 years; P < .05). Food allergies were also associated with eczema, but not with sensitization to aero-allergens or rhinitis.
The high risk of food allergies in children who were liver transplant recipients was associated with eczema and asthma, but not rhinitis. The most frequent food allergens associated with asthma were milk, eggs, and peanuts.
Background
LTX in children is associated with increased risk of food allergy, and the mechanisms underlying this are unknown. We wanted to study whether plasma cytokine profile differed in liver ...transplanted children, with and without food allergy, and whether it differed from untransplanted children with CLD.
Methods
Plasma cytokines, total and specific IgE in nine patients with food allergy were compared with 13 patients without food allergy following LTX, and also with seven untransplanted patients with CLD.
Results
No difference was found in the cytokine profile between liver transplanted patients with and without food allergy. Transplanted patients with food allergy having received a prescription of epinephrine had a significantly higher total IgE (2033 234‐2831 vs 10 5‐41 IU/L, P = .002) and MIP‐1b (52 37‐96 vs 36 32‐39, P = .035) compared with transplanted patients without food allergy. Two patients with severe food allergy responded favorably to conversion from tacrolimus‐based immunosuppression to MMF and corticosteroids with reduction in clinical symptoms, total IgE, specific IgE, IL‐1ra, IL‐4, RANTES, PDGF, MIP‐1a, and TNFα. The transplantation group had higher levels of IL‐1b, IL‐5, IL‐7, IL‐13, GCSF, IFNγ, and MIP‐1a compared with the CLD group.
Conclusions
No overall difference was found in plasma cytokine profile between patients with and without food allergy. Patients with severe food allergy had significant elevation of MIP‐1b. Discontinuation of tacrolimus reduced total and specific IgE and changed plasma cytokine profile. The plasma cytokine profile in liver transplanted children was different compared with children with CLD.
Objectives
Parenteral nutrition (PN) is used for patients of varying ages with intestinal failure to supplement calories. Premature newborns with low birth weight are at a high risk for developing PN ...associated liver disease (PNALD) including steatosis, cholestasis, and gallbladder sludge/stones. To optimize nutrition regimens, models are required to predict PNALD.
Methods
We have exploited induced pluripotent stem cell derived liver organoids to provide a testing platform for PNALD. Liver organoids mimic the developing liver and contain the different hepatic cell types. The organoids have an early postnatal maturity making them a suitable model for premature newborns. To mimic PN treatment we used medium supplemented with either clinoleic (80% olive oil/20% soybean oil) or intralipid (100% soybean oil) for 7 days.
Results
Homogenous HNF4a staining was found in all organoids and PN treatments caused accumulation of lipids in hepatocytes. Organoids exhibited a dose dependent decrease in CYP3A4 activity and expression of hepatocyte functional genes. The lipid emulsions did not affect overall organoid viability and glucose levels had no contributory effect to the observed results.
Conclusions
Liver organoids could be utilized as a potential screening platform for the development of new, less hepatotoxic PN solutions. Both lipid treatments caused hepatic lipid accumulation, a significant decrease in CYP3A4 activity and a decrease in the RNA levels of both CYP3A4 and CYP1A2 in a dose dependent manner. The presence of high glucose had no additive effect, while Clinoleic at high dose, caused significant upregulation of interleukin 6 and TLR4 expression.
What is Known
Infants receiving parenteral nutrition (PN) are at risk of developing PN associated liver disease (PNALD) which include steatosis, cholestasis, and gallbladder sludge/stones.
Composition of lipid emulsions affect risk of PNALD.
What is New
Induced pluripotent stem cell (iPSC) derived liver organoids can provide a testing platform for PN.
High concentrations of both intralipid and clinoleic decreased Cytochrome P450 3A4 (CYP3A4) activity.
High concentrations of intralipid and clinoleic reduced the expression of CYP1A2 and CYP3A4 RNA.
High concentrations of clinoleic caused significant upregulation of interleukin 6 expression.
To assess longitudinal neurocognitive development after liver transplantation and evaluate factors associated with neurocognitive performance.
Data from neurocognitive testing of 65 children (aged ...<18 years) who underwent liver transplantation at Oslo University Hospital between 1995 and 2018 were collected from the testing program after transplantation. The parent-reported version of the Behavior Rating Inventory of Executive Function was used to assess executive function.
A total of 104 neurocognitive tests were conducted on 65 patients. At the first test, conducted at a median of 4.1 years (IQR, 1.5-5.3 years) after transplantation and at a median age of 6.7 years (IQR, 5.4-10.5 years), the mean full-scale IQ (FSIQ) was 91.7 ± 14, and the mean verbal comprehension index was 92.0 ± 14.5. In the 30 patients tested more than once, there was no significant difference in FSIQ between the first test at a median age of 5.8 years (IQR, 5.2-8.5 years) and the last test at a median age of 10.8 years (IQR, 9.8-12.9 years) (87.4 ± 12.9 vs 88.5 ± 13.2; P = .58). Compared with the patients who underwent transplantation a age >1 year (n = 35), those who did so at age <1 year (n = 30) had a lower FSIQ (87.1 ± 12.6 vs 96.6 ± 13.8; P = .005) and lower verbal comprehension index (87.3 ± 13.8 vs 95.4 ± 13.0; P = .020). Age at transplantation (P = .005; adjusted for cholestasis: P = .038) and transfusion of >80 mL/kg (P = .004; adjusted for age at transplantation: P = .046) were associated with FSIQ.
Young age at transplantation and large blood transfusions during transplantation are risk factors for poor neurocognitive performance later in life. Children who undergo transplantation before 1 year of age have significantly lower neurocognitive performance compared with those who do so later in childhood. Cognitive performance did not improve over time after transplantation.
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