Liver Injury In Children Research Articles

Analysis of the occurrence and liver function characteristics of arsenic-associated liver injury during the treatment of pediatric patients with acute promyelocytic leukemia.

Liver injury during arsenic treatment for acute promyelocytic leukemia was previously reported in adults, but not comprehensively in children until now. This study aims to investigate liver injury in pediatric patients with APL, changes in liver function during treatment, and compare the effects of Arsenic trioxide (ATO) and Realgar-Indigo naturalis formula (RIF) on liver function. One hundred and eighty-six patients with 3076 patient tests were analyzed, who were enrolled in the Chinese Children's Leukemia Group (CCLG)-APL2016 Protocol database between November 2016 and November 2018 in 38 hospitals across China(ChiCTR-OIN-17011227). Twenty of 164 patients (12.2%) suffered from liver injury after treatment with arsenic. In addition, sixteen (80%) cases of liver injury occurred during the induction period of treatment. What's not disheartening was that 18 (90%) cases of liver injury were transient, occurring at a median time of 17 days after exposure to arsenic. More importantly, the risk of liver injury associated with RIF was not higher than that associated with ATO (RR = 0.854, 95% CI: 0.292-2.495). Otherwise, the ALP of 18 cases of liver injury was not higher than the ULN of ALP. Thus, the incidence of liver injury associated with arsenic in pediatric patients with APL was similar to that in adult patients and the risk of liver injury associated with RIF was not higher than that associated with ATO. Since ALP was not higher in pediatric APL patients with liver injury, further research is needed to explore whether ALP is an index of liver injury in children.

A Single-center Clinical Analysis of Drug-Induced Liver Injury in Children with Acute Leukemia

A Single-center Clinical Analysis of Drug-Induced Liver Injury in Children with Acute Leukemia

Whole-exome sequencing for genetic diagnosis of idiopathic liver injury in children.

Genome-wide approaches, such as whole-exome sequencing (WES), are widely used to decipher the genetic mechanisms underlying inter-individual variability in disease susceptibility. We aimed to dissect inborn monogenic determinants of idiopathic liver injury in otherwise healthy children. We thus performed WES for 20 patients presented with paediatric-onset recurrent elevated transaminases (rELT) or acute liver failure (ALF) of unknown aetiology. A stringent variant screening was undertaken on a manually-curated panel of 380 genes predisposing to inherited human diseases with hepatobiliary involvement in the OMIM database. We identified rare nonsynonymous variants in nine genes in six patients (five rELT and one ALF). We next performed a case-level evaluation to assess the causal concordance between the gene mutated and clinical symptoms of the affected patient. A genetic diagnosis was confirmed in four rELT patients (40%), among whom two carried novel mutations in ACOX2 or PYGL, and two had previously-reported morbid variants in ABCB4 or PHKA2. We also detected rare variants with uncertain clinical significance in CDAN1, JAG1, PCK2, SLC27A5 or VPS33B in rELT or ALF patients. In conclusion, implementation of WES improves diagnostic yield and enables precision management in paediatric cases of liver injury with unknown aetiology, in particular recurrent hypertransaminasemia.

Glutamate Dehydrogenase Enzyme Can Early Predict Liver Injury in Children with COVID-19

Glutamate Dehydrogenase Enzyme Can Early Predict Liver Injury in Children with COVID-19

Drug-induced liver injury in children: A nationwide cohort study from China

Background & AimsCurrently, there is limited knowledge on the clinical profile of drug induced liver injury (DILI) in Chinese children. We aimed to assess the clinical characteristics, suspected drugs, and outcomes associated with pediatric DILI in China. MethodsThis nationwide, multi-center, retrospective study, conducted between 2012 and 2014, analyzed 25,927 cases of suspected DILI at 308 medical centers using the inpatient medical register system. Utilizing the Roussel Uclaf Causality Assessment Method (RUCAM) score, only patients with scores>6 or diagnosed with DILI by at least two experts after scoring <6 were included in the analysis. Among them, 460 cases met the European Association for the Study of Liver (EASL) biochemical criteria. The study categorized children into three age groups: toddlers (≥30 days to <6 years old), school-age children (6 to <12 years old), and adolescents (12 to <18 years old). ResultsHepatocellular injury was the predominant clinical classification, accounting for 63% of cases, with 34% of these cases meeting Hy's law criteria. Adolescents comprised the majority of children with moderate/severe DILI (65%). Similarly, adolescents faced a significantly higher risk of severe liver injury compared to younger children (adjusted odd ratio [aOR]=4.75, p =.002). The top three most frequently prescribed drug classes across all age groups were antineoplastic agents (25.9%), antimicrobials (21.5%), and traditional Chinese medicine (TCM, 13.7%). For adolescents, the most commonly suspected drugs were antituberculosis drugs (22%) and TCM (23%). ConclusionAdolescents are at a greater risk of severe and potentially fatal liver injury compared to younger children. Recognizing the risk of pediatric DILI is crucial for ensuring safe medical practices.

Liver injury in children: signal analysis of suspected drugs based on the food and drug administration adverse event reporting system

BackgroundEvidence of drug-induced liver injury is abundant in adults but is lacking in children. Our aim was to identify suspected drug signals associated with pediatric liver injury.MethodsHepatic adverse events (HAEs) among children reported in the Food and Drug Administration Adverse Event Reporting System were analyzed. A descriptive analysis was performed to summarize pediatric HAEs, and a disproportionality analysis was conducted by evaluating reporting odds ratios (RORs) and proportional reporting ratios to detect suspected drugs.ResultsHere, 14,143 pediatric cases were reported, specifically 49.6% in males, 45.1% in females, and 5.2% unknown. Most patients (68.8%) were 6–18 years old. Hospitalization ranked first among definite outcomes (7,207 cases, 37.2%). In total, 264 disproportionate drug signals were identified. The top 10 drugs by the number of reports were paracetamol (1,365; ROR, 3.6; 95% confidence interval (CI), 3.4–3.8), methotrexate (878; ROR, 2.5; 95% CI, 2.3–2.7), vincristine (649; ROR, 3.0; 95% CI, 2.8–3.3), valproic acid (511; ROR, 3.2; 95% CI, 2.9–3.6), cyclophosphamide (490; ROR, 2.4; 95% CI, 2.2–2.6), tacrolimus (427; ROR, 2.4; 95% CI, 2.2–2.7), prednisone (416; ROR, 2.1; 95% CI, 1.9–2.3), prednisolone (401; ROR, 2.3; 95% CI, 2.1–2.5), etoposide (378; ROR, 2.3; 95% CI, 2.1–2.6), and cytarabine (344; ROR, 2.8; 95% CI, 2.5–3.2). After excluding validated hepatotoxic drugs, six were newly detected, specifically acetylcysteine, thiopental, temazepam, nefopam, primaquine, and pyrimethamine.ConclusionsThe hepatotoxic risk associated with 264 signals needs to be noted in practice. The causality of hepatotoxicity and mechanism among new signals should be verified with preclinical and clinical studies.

Clinicopathologic Features of Severe Acute Hepatitis Associated With Adenovirus Infection in Children.

A recent increase in reports of severe acute hepatitis of unknown etiology in children is under investigation. Although adenovirus has been frequently detected, its role remains unclear, and systematic histopathologic analysis is lacking. We conducted a retrospective study of 11 children hospitalized between October 2021 and May 2022 with unexplained acute hepatitis and concurrent adenovirus infection. Liver biopsies collected shortly after admission demonstrated moderately to severely active hepatitis in 8/11 (73%) cases, characterized by marked portal mixed inflammation, moderate-to-severe interface activity, and milder lobular inflammation. Clusters of plasma cells were present in 6/11 (55%) cases, mimicking autoimmune hepatitis. Semiquantitative scoring of 17 discrete histologic features found that greater degrees of portal inflammation, interface activity, bile duct injury, bile ductular reaction, lobular inflammation, Kupffer cell activation, and hepatocyte focal necrosis were significantly more common in these cases in comparison to the control group of unexplained acute severe hepatitis without adenovirus infection. Liver biopsy immunohistochemistry was negative for adenovirus in all cases. Polymerase chain reaction testing of liver tissue was positive for the enteric adenovirus serotypes 41 (species F) in 10/11 (91%) cases. An immunoprofile study of hepatic infiltrating lymphocytes in 1 patient revealed the presence of large numbers of CD3 + and CD4 + lymphocytes. Nine patients received supportive treatment without steroids and recovered without the need for liver transplantation. In summary, liver injury in children with severe acute hepatitis and adenovirus infection is characterized by a hepatitic pattern that resembles severe autoimmune hepatitis and may represent an immune-mediated process associated with viral infection.

Spectrum of COVID-19-induced liver injury in children

Deranged liver functions, which mainly raised alanine aminotransferase (ALT) and aspartate aminotransferase (AST), have been reported in 14%–53% of coronavirus disease 2019 (COVID-19) patients without known liver disease. Patients with the severe disease showed higher frequency and degree of liver dysfunction, while in milder cases the liver injury was transient. The mechanisms of hepatic injury include immune-mediated inflammation and hypoxic injury due to severe pneumonia and drug usage. It is also postulated that expression of the ACE2 receptor on cholangiocytes may predispose to cholestatic injury. In this study, it was aimed to review the spectrum of COVID-19-induced liver injury in children.

COVID-19 and liver dysfunction in children: Current views and new hypotheses.

Coronavirus disease 2019 (COVID-19) poses an extremely serious global impact on public healthcare for individuals of all ages, including children. Increasing evidence has shown that liver abnormalities are commonly found in children with COVID-19, and age-related features in innate and adaptive response have been demonstrated. However, there are few reports and studies on COVID-19 related liver injury in children, and the data are scattered. So that many contradictions have arose. This situation is not only due to the serious ethical issues in studying pediatric patients with COVID-19, but also because of the short duration and wide coverage of the COVID-19 epidemic, the severity and complexity of clinical cases varied, as did the inclusion criteria for case reporting and patient outcomes. Therefore, we totaled the incidences, characteristics and pathomechanism of liver injury in children since the COVID-19 outbreak. The etiology of COVID-19-related liver injury is divided into three categories: (1) The direct mechanism involves severe acute respiratory syndrome coronavirus 2 binding to angiotensin-converting enzyme 2 in the liver or bile duct to exert direct toxicity; (2) the indirect mechanisms include an inflammatory immune response and hypoxia; and (3) COVID-19-related treatments, such as mechanical ventilation and antiviral drugs, may cause liver injury. In summary, this minireview provides fundamental insights into COVID-19 and liver dysfunction in children.

Liver Injury in Children with COVID-19: A Systematic Review

Background: The rapid global spread of coronavirus disease 2019 (COVID-19) infection has become a major health issue with high morbidity and mortality rates. COVID-19 in children showed different unique presentations. Besides respiratory symptoms, a growing body of evidence indicates multi-organ manifestation, including liver involvement. In this regard, several data supported an association between COVID-19 infection and liver injury in adults, while on the other hand, there is compelling but currently limited evidence in children. In this systematic review, we summarize data of updated literature regarding the evidence of acute liver injury in children with COVID-19. Methods: Online scientific articles were explored on PubMed and Google Scholar databases using keywords. The systematic review was performed under the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines Results: The literature search yielded 238 articles, of which 16 were identified as relevant to the topic and met the inclusion criteria. A total of 564 pediatric patients were confirmed positive for COVID-19 by PCR examination, involving 298 (52.9%) boys and 266 (47.1%) girls with an age range of 1 day - 17 years. Liver injuries have been reported in pediatric COVID-19 patients, with prevalence ranging from 1.5 to 52%. Conclusion: SARS-CoV-2 virus infection in children shows a unique presentation. Several reports suggest that liver injury correlates with the severity of COVID-19 disease. Therefore, monitoring liver function in COVID-19 patients is important to assess the prognosis.

Gastrointestinal manifestations in children with COVID-19 infection: Retrospective tertiary center experience.

The majority of pediatric severe acute respiratory syndrome coronavirus 2 (COVID-19) cases demonstrate asymptomatic, mild or moderate disease. The main symptoms in children with COVID-19 are respiratory symptoms but some patients develop gastrointestinal symptoms and liver injury. We aim to review gastrointestinal symptoms and liver injury in children with confirmed COVID-19 infection. This is a retrospective case note review of children with positive COVID-19 nasal Polymerase Chain Reaction aged 0-18 years admitted to a tertiary pediatric hospital from March 1st till June 1st 2020. 180 children were identified. Mean age was 5 years (Range: 0.01-17), the majority of patients were school aged (30%). Patients were mainly from East Asia 81 (45%) and Arabs 67 (37%). Gastrointestinal symptoms were encountered in 48 (27%) patients and 8 (4%) patients had only Gastrointestinal symptoms with no associated fever or respiratory symptoms. Liver injury was seen in 57 (32%) patients. Patients with fever and cough were more likely to have gastrointestinal symptoms (P = <0.001 and 0.004 respectively). Fever was more likely to be associated with liver injury (P = 0.021). Children with abdominal pain were more likely to have elevated C-Reactive Protein (P = 0.037). Patients with diarrhea and vomiting were more likely to have elevated procalcitonin (P = 0.034 and 0.002 respectively). Children with Gastrointestinal symptoms were not more likely to be admitted to Pediatric Intensive Care Unit (P = 0.57). COVID-19 infection in children can display gastrointestinal symptoms at initial presentation. Additionally, gastrointestinal symptoms can be the only symptoms patients display. We demonstrated that children with gastrointestinal symptoms and liver injury can develop more severe COVID-19 disease and are more likely to have fever, cough, and raised inflammatory markers. Identifying children with gastrointestinal manifestations needs to be part of the initial screening assessment of children.What is known?• Pediatric COVID-19 cases mostly demonstrate asymptomatic, mild or moderate disease.• The symptoms in children are mainly respiratory but some display gastrointestinal symptoms.• Children with COVID-19 display increased gastrointestinal symptoms when compared to adults.What is new?• Children with COVID-19 displaying gastrointestinal symptoms are more likely to have fever, cough and elevated inflammatory markers.• Children with liver injury are more likely to develop fever.• Children with gastrointestinal involvement in COVID-19 are more likely to demonstrate more severe disease but are not more likely to be admitted to PICU.

Severe liver injury affects the outcomes and length of hospital stay in children with community-acquired pneumonia.

The present study was undertaken to evaluate the association between liver injury and clinical parameters, outcomes and length of stay (LOS) in hospital in children with community-acquired pneumonia (CAP). Clinical data and laboratory indicators of 2,573 children with CAP were analyzed. The association between liver injury and clinical parameters, outcomes and LOS was then analyzed. Higher liver injury class was associated with higher incidence of severe CAP, comorbidities, hypoxia, requirement for mechanical ventilation, 30-day mortality and intensive care unit admission, and higher indicators of inflammation (C-reactive protein, procalcitonin and white blood cell count), longer LOS, faster respiratory rate and pulse rate, and lower age, serum albumin levels, monocyte and lymphocyte counts. Severe liver injury was identified as an independent factor for 30-day mortality and prolonged LOS in children with CAP. Higher liver injury class was associated with a lower cumulative survival rate (p=0.0004), and log-rank test for trend was used to demonstrate the association of each injury class with 30-day mortality (p=0.0002). Several parameters were associated with liver injury in children with CAP. Severe liver injury was found to be an independent factor for 30-day mortality and LOS in children with CAP.

Association of Prenatal Exposure to Endocrine-Disrupting Chemicals With Liver Injury in Children

Prenatal exposures to endocrine-disrupting chemicals (EDCs) may increase the risk for liver injury in children; however, human evidence is scarce, and previous studies have not considered potential EDC-mixture effects. Furthermore, the association between prenatal EDC exposure and hepatocellular apoptosis in children has not been studied previously. To investigate associations of prenatal exposure to EDC mixtures with liver injury risk and hepatocellular apoptosis in childhood. This prospective cohort study used data collected from April 1, 2003, to February 26, 2016, from mother-child pairs from the Human Early-Life Exposome project, a collaborative network of 6 ongoing, population-based prospective birth cohort studies from 6 European countries (France, Greece, Lithuania, Norway, Spain, and the UK). Data were analyzed from April 1, 2021, to January 31, 2022. Three organochlorine pesticides, 5 polychlorinated biphenyls, 2 polybrominated diphenyl ethers (PBDEs), 3 phenols, 4 parabens, 10 phthalates, 4 organophosphate pesticides, 5 perfluoroalkyl substances, and 9 metals. Child serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), and CK-18 were measured at 6 to 11 years of age. Risk for liver injury was defined as having ALT, AST, and/or GGT levels above the 90th percentile. Associations of liver injury or cytokeratin 18 (CK-18) levels with each chemical group among the 45 EDCs measured in maternal blood or urine samples collected in pregnancy were estimated using 2 complimentary exposure-mixture methods: bayesian weighted quantile sum (BWQS) and bayesian kernel machine regression. The study included 1108 mothers (mean [SD] age at birth, 31.0 [4.7] years) and their singleton children (mean [SD] age at liver assessment, 8.2 [1.6] years; 598 [54.0%] boys). Results of the BWQS method indicated increased odds of liver injury per exposure-mixture quartile increase for organochlorine pesticides (odds ratio [OR], 1.44 [95% credible interval (CrI), 1.21-1.71]), PBDEs (OR, 1.57 [95% CrI, 1.34-1.84]), perfluoroalkyl substances (OR, 1.73 [95% CrI, 1.45-2.09]), and metals (OR, 2.21 [95% CrI, 1.65-3.02]). Decreased odds of liver injury were associated with high-molecular-weight phthalates (OR, 0.74 [95% CrI, 0.60-0.91]) and phenols (OR, 0.66 [95% CrI, 0.54-0.78]). Higher CK-18 levels were associated with a 1-quartile increase in polychlorinated biphenyls (β, 5.84 [95% CrI, 1.69-10.08] IU/L) and PBDEs (β, 6.46 [95% CrI, 3.09-9.92] IU/L). Bayesian kernel machine regression showed associations in a similar direction as BWQS for all EDCs and a nonlinear association between phenols and CK-18 levels. With a combination of 2 state-of-the-art exposure-mixture approaches, consistent evidence suggests that prenatal exposures to EDCs are associated with higher risk for liver injury and CK-18 levels and constitute a potential risk factor for pediatric nonalcoholic fatty liver disease.

Incidence, predictors and outcome of sepsis-associated liver injury in children: a prospective observational study.

Sepsis-associated liver injury (SALI) occurs as a result of the systemic and microcirculatory changes that happen because of sepsis. Its prognostic significance in the paediatric population is unclear. We enrolled all children < 19 years, admitted between July, 2020 and July, 2021 to the paediatric unit (ward or intensive care unit) with a diagnosis of sepsis for this study. Clinical and biochemical parameters of children with sepsis who developed SALI were compared with those without SALI to determine the risk factors of SALI and its impact on in-hospital mortality. A total of 127 children, median age 72 (1–204) months, 74 males were included. SALI developed in 45 (31.3%) at a median 1 (1–13) days after the diagnosis of sepsis. The SALI pattern was cholestatic in 18 (40%), hepatocellular in 17 (37.7%) and hypoxic hepatitis in 10 (22.3%). Paediatric sequential organ failure assessment (pSOFA) was an independent predictor of SALI — OR 1.17 (95% CI 1.067–1.302), p = 0.001. A pSOFA score of > 9.5 predicted the development of SALI with 66.7% sensitivity and 77.1% specificity. SALI was an independent predictor of mortality in children with sepsis — OR 1.9 (95% CI 1.3–3.4), p = 0.01. Conclusions: SALI develops in 45 (31.3%) with sepsis. A higher pSOFA score is associated with SALI. Children who develop SALI have a ~ twofold higher risk of mortality than those without SALI.What is Known:• During the process of sepsis, the liver plays a role by scavenging bacteria and producing inflammatory mediators. However, at times the liver itself becomes a target of the dysregulated inflammatory response. This is known as sepsis-associated liver injury (SALI).• The incidence of sepsis-associated liver injury and its prognostic significance in children is not known..What is New:• SALI develops in one-third children with sepsis and is associated with a higher pSOFA score.• Children who develop SALI have a higher risk of mortality. Supplementary informationThe online version contains supplementary material available at 10.1007/s00431-022-04374-2.

Therapeutic Effect of Bicyclol Coupled with Aspirin Nanopreparation on Liver Function Damage Caused by Epstein‐Barr Virus Infection in Children

The aim of study effective treatment is to reach the appropriate part of the body and then maintain the required drug concentration at sufficient intervals in order to achieve the clinical therapeutic effect. Problem of the Study. Biological barrier hinders the flow of most drugs from the blood to the focus. Methods of the Study. A novel nanopreparation for inhibition of Epstein‐Barr virus (EBV) was developed based on poly (lactic‐co‐glycolic acid) (PLGA) nanodrug carriers loaded with bicyclic alcohol (BA) and aspirin (Asp) (PLGA‐BA/Asp). Among them, the addition of PLGA can effectively improve the low solubility of BA and poor oral availability. Results have revealed that PLGA‐BA/Asp is a multifunctional therapeutic drug that integrates antivirus, treatment of liver damage, and regulation of the immune system. This discovery provides a new treatment method for the treatment of liver injury in children with EBV infection.

Erratum to ibuprofen induced Stevens-Johnson syndrome and liver injury in children: a case report

[This corrects the article DOI: 10.21037/tp-21-8.].

A Risk Scoring Model for High-Dose Methotrexate-Induced Liver Injury in Children With Acute Lymphoblastic Leukemia Based on Gene Polymorphism Study.

A study on 70 acute lymphoblastic leukemia (ALL) children (age ≤16 years) treated with high-dose methotrexate (HD-MTX) in Sichuan Provincial People’s Hospital was conducted. The aim of the study was to establish a risk-scoring model to predict HD-MTX-induced liver injury, considering gene polymorphisms’ effects. Data screening was performed through t-test, chi-square test, and ridge regression, and six predictors were identified: age, MTRR_AA, MTRR_AG, SLCO1B1_11045879_CC, albumin_1 day before MTX administration, and IBIL_1 day before MTX administration (p < 0.1). Then, the risk-scoring model was established by ridge regression and evaluated the prediction performance. In a training cohort (n = 49), the area under the curve (AUC) was 0.76, and metrics including accuracy, precision, sensitivity, specificity, positive predictive value, and negative predictive value were promising (0.86, 0.81, 0.76, 0.91, 0.81, 0.88, respectively). In a test cohort (n = 21), the AUC was 0.62 and negative predictive value was 0.80; other evaluation metrics were not satisfactory, possibly due to the limited sample size. Ultimately, the risk scores were stratified into three groups based on their distributions: low- (≤48), medium- (49–89), and high-risk (>89) groups. This study could provide knowledge for the prediction of HD-MTX-induced liver injury and reference for the clinical medication.

Retrospective assessment of developing liver injuries in children brought to the emergency room due to the blunt abdominal trauma over the past 10 years; a single -center experience.

OBJECTIVE: In this study it was aimed to evaluate the types of trauma, accompanying solid organ injuries, treatments, and treatment outcomes in children admitted to our clinic in the last 10 years due to blunt liver trauma.&#x0D; MATERIAL AND METHOD: The data of 47 patients who were involved in liver injuries owing to blunt abdominal trauma between July 2010-May 2020 assessed retrospectively.&#x0D; RESULTS: There were 30 (63.8%) male, 17 (36.2%) female patients who had carried out with blunt liver injuries between 1-17 (7.8±5.8) years were involved in this study. The induces of these injuries included traffic accidents 29 ( 61.7%), falls from height 12 25.5 %), bicycle accidents 4 (8.5%), objects falling on the body 1(2.1%), and 1(%2.1) after the assault. Twenty-seven (57.4%) of the patients had isolated liver injuries and 20 (42.6%) of other organ injuries.. Liver injuries were 8 patients (17.3%) stage I, 12 patients (26%) stage II, 18 patients (38.2%) stage III, 8 patients (17%) stage IV, 1 patient (2%) stage V. While all patients of stage I and II were treated conservatively, 4 patients (22.2%) who underwent surgery were stage III, 3 patients (37.5%) were stage IV and 1 patient (100%) were stage V. There was an additional ileum perforation in 2 patients in stage III and 1 patient in stage IV who underwent surgery. Thirty-nine patients (83%) were carrıed out by conservatively in these series of liver injury, whereas eight patients (17%) who had unstable vital signs underwent surgery. The mortality rate, duration of stay in intensive care and hospital, and the number of blood transfusions were higher in surgically managed patients, while hemoglobin level and blood pressure were particularly lower in surgically conducted patients.&#x0D; CONCLUSION: Conservative treatment method should be chosen in patients with a liver injury who have stable hemodynamics after blunt trauma. The shorter duration of hospital stay, less blood transfusion requirement, and lower morbidity and mortality rates are important reasons for this method to be preferred.

Prenatal exposure to lipophilic endocrine-disrupting chemicals and liver injury in children using chemical mixture approaches

BACKGROUND AND AIM: Exposure to Endocrine Disrupting Chemicals (EDC) may increase liver injury, but few studies have examined these associations in children and most focused on a single chemical group. We evaluated the associations between a wide range of prenatal EDC exposures and child liver injury. METHODS: We studied 1108 healthy children from the Human Early-Life Exposome (HELIX) project, a collaborative network of six established longitudinal population-based birth cohort studies in Europe. Thirty lipophilic EDCs (including 3 organochlorine pesticides, 5 polychlorinated-biphenyl, 2 polybrominated-diphenyl-ethers [PBDEs], 5 high molecular weight phthalates (HMWP), 5 low molecular weight phthalates, 6 phenols and 4 organophosphate pesticides) were measured in maternal pregnancy blood or urine. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT) and cytokeratin 18 (CK18) were measured in child serum at follow-up between age 6-11 years. Liver injury was defined as having any liver enzyme (ALT, AST or GGT) above the 90th percentile. We used Bayesian generalized linear mixed regressions (Bglmr) to estimate associations of individual chemicals, Bayesian Weighted Quantile Sum (BWQS) and Bayesian Kernel Machine Regression (BKMR) to assess the overall association of each chemical group with liver injury and CK18, adjusting for confounders. RESULTS:BWQS results indicated that organochlorine pesticides and PBDEs were associated with increased odds of liver injury (OR[95%CI] by chemical mixture quartile increase=1.44[1.23, 1.72] and 1.59[1.37, 1.90], respectively); whereas HMWP were associated with decreased odds of liver injury (OR[95%CI]=0.71[0.59, 0.85]). A quartile increase of PBDEs was positively associated with CK18 (Estimate[95%CI]=5.33 Units/Liter [2.52,8.16]). Bglmr and BKMR showed associations in same direction as the BWQS results. There was evidence of effect heterogeneity by sex for organochlorine pesticides and HMWPs with liver injury status. CONCLUSIONS:Using multiple chemical mixture approaches we found that prenatal exposures to persistent pollutants, especially to organochlorine compounds, and PBDEs, may be associated with increased risk for liver injury in childhood. KEYWORDS: Chemical exposures, Endocrine disrupting chemicals, Mixtures analysis, Modeling, Environmental epidemiology

Ibuprofen induced Stevens-Johnson syndrome and liver injury in children: a case report

Stevens-Johnson syndrome (SJS) is a disorder that causes severe damage to the skin and mucous membranes with bullous and erosive properties. Drug-induced liver injury (DILI) is closely related to non-steroidal anti-inflammatory drugs (such as ibuprofen). Liver injury caused by ibuprofen is often related to overdose, and liver injury caused by normal dose is rare, and there are individual differences in different situations. In this case, a child developed SJS and acute liver injury after treatment with ibuprofen suspension. We described the characteristics of related adverse reactions induced by ibuprofen, and analyzed the relationship between SJS caused by the drug and related drug genes. Glucocorticoids and antihistamines were used to treat dermatitis, reduced glutathione (GSH) to protect the liver and plasma exchange detoxification. Finally, the patient’s dermatitis healed and the liver injury was significantly improved. Many studies have suggested that DILI may be related to human leukocyte antigen (HLA) genotyping. The detection of drug-related genes revealed that the SJS and liver damage caused by ibuprofen might have been related to the positive HLA-B*5801. This article suggests that attention should be paid to checking liver function indicators after taking ibuprofen, and genetic screening can be used to reduce the risk of gene-related adverse reactions when necessary.