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Background: Cystic fibrosis-related liver disease (CFRLD) is a health problem that can affect as many as 30-40% of cystic fibrosis patients by the age of 12 years. We studied the epidemiology of CFRLD thanks to the first exclusively pediatric CFRLD patient registry to date., Methods: Descriptive cross-sectional study. Information from medical records from January 2018 to December 2020 is collected. CFRLD was classified according to the European Society of Paediatric Gastroenterology, Hepatology and Nutrition 2017 criteria., Results: Data were collected from 168 pediatric patients diagnosed with CFRLD (90.5% liver involvement without cirrhosis and 8.5% multinodular cirrhosis)., Conclusion: In this national registry, including exclusively pediatric population, liver disease is diagnosed around 7 years of age. Liver involvement without cirrhosis is the most frequent finding among our patients but about 9% of the patients already had cirrhosis. CFRLD is one of the challenges faced by pediatric gastroenterologists in the future and national registries give us the opportunity to further study and broaden our knowledge., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Epstein-Barr virus (EBV) specific T-cell response measurement can help adjust immunosuppression in transplant patients with persistent infections. We aim to define T-cell responses against EBV in a cohort of pediatric liver-transplant patients., Methods: Thirty-eight immunosuppressed pediatric liver-transplant patients (IP) and 25 EBV-seropositive healthy-adult controls (HC) were included in our cross-sectional study. Based on their EBV serological (S) and viral load (VL) status, patients were categorized into IP-S NEG , IP-S POS VL NEG and IP-S POS VL POS groups. T-cell response was assessed at two timepoints by stimulating cells with EBV peptides (PepTivator ® ) and performing intracellular-cytokine and activation-induced marker staining. Background subtraction was used to determine EBV-specific T-lymphocyte frequency., Results: Polyfunctional CD8+ T cells indicated previous EBV contact (IP-S NEG 0.00% vs IP-S POS 0.04% and HC 0.02%; p=0.001 and p=0.01, respectively). Polyfunctional CD8+CD107a+IFNɣ+IL2-TNFα- profile was increased in serology-positive (IP-S NEG 0.01% vs IP-S POS 0.13% and HC 0.03%; p=0.01 and p=0.50, respectively) and viral-load positive (IP-S POS VL POS 0.43% vs IP-S POS VL NEG 0.07% and HC 0.03%; p=0.03 and p=0.001, respectively) patients. Central-memory cells were increased among serology-positive adults (IP-S NEG 0.00% vs IP-S POS 0.13% and HC 4.33%; p=0.58 and p=0.002, respectively). At the second timepoint, IP-S NEG patients remained negative (first visit 0.01% vs second visit 0.00%, p=0.44). On the other hand, IP-S POS VL POS patients had cleared viral loads and, subsequently, decreased polyfunctional CD8+CD107a+IFNɣ+IL2-TNFα- cells (first visit 0.43% vs second visit 0.10%, p=0.81)., Conclusion: Polyfunctional CD8+ EBV-specific T-cell response allows detecting EBV previous contact in liver-transplant children. %CD8+CD107a+IFNɣ+IL2-TNFα- is increased in patients with positive viral loads. Central memory CD4+ T-cell population more effectively determines prior EBV-exposure in adults., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Cuesta-Martín de la Cámara, Torices-Pajares, Miguel-Berenguel, Reche-Yebra, Frauca-Remacha, Hierro-Llanillo, Muñoz-Bartolo, Lledín-Barbacho, Gutiérrez-Arroyo, Martínez-Feito, López-Granados and Sánchez-Zapardiel.)

Pediatric liver transplantation (PLTx) is commonly associated with extensive antibiotic treatments that can produce gut microbiome alterations and open the way to dominance by multidrug-resistant organisms (MDROs). In this study, the relationship between intestinal Relative Loads (RLs) of β-lactamase genes, antibiotic consumption, microbiome disruption, and the extraintestinal dissemination of MDROs among PLTx patients is investigated. 28 PLTx patients were included, from whom 169 rectal swabs were collected. Total DNA was extracted and bla CTX-M-1-Family , bla OXA-1 , bla OXA-48 , and bla VIM were quantified via quantitative polymerase chain reaction (qPCR) and normalized to the total bacterial load ( 16SrRNA ) through LogΔΔCt to determine the RLs. 16SrRNA sequencing was performed for 18 samples, and metagenomic sequencing was performed for 2. Patients' clinical data were retrieved from the hospital's database. At least one of the genes tested were detected in all of the patients. The RLs for bla CTX-M-1-Family , bla OXA-1 , bla OXA-48 , and bla VIM were higher than 1% of the total bacterial population in 67 (80.73%), 56 (78.87%), 57 (77.03%) and 39 (61.9%) samples, respectively. High RLs for bla CTX-M-1-Family , bla OXA-1 , and/or bla OXA-48 , were positively associated with the consumption of carbapenems with trimethoprim-sulfamethoxazole and coincided with low diversity in the gut microbiome. Low RLs were associated with the consumption of noncarbapenem β-lactams with aminoglycosides ( P < 0.05). Extraintestinal isolates harboring the same gene(s) as those detected intraintestinally were found in 18 samples, and the RLs of the respective swabs were high. We demonstrated a relationship between the consumption of carbapenems with trimethoprim-sulfamethoxazole, intestinal dominance by MDROs and extraintestinal spread of these organisms among PLTx patients. IMPORTANCE In this study, we track the relative intestinal loads of antibiotic resistance genes among pediatric liver transplant patients and determine the relationship between this load, antibiotic consumption, and infections caused by antibiotic-resistant organisms. We demonstrate that the consumption of broad spectrum antibiotics increase this load and decrease the gut microbial diversity among these patients. Moreover, the high loads of resistance genes were related to the extraintestinal spread of multidrug-resistant organisms. Together, our data show that the tracking of the relative intestinal loads of antibiotic resistance genes can be used as a biomarker that has the potential to stop the extraintestinal spread of antibiotic-resistant bacteria via the measurement of the intestinal dominance of these organisms, thereby allowing for the application of preventive measures.

Wilson's disease can manifest with symptoms of liver disease or neuropsychiatric disorders in children and adults. This autosomal recessive disorder is caused by a copper metabolism disorder due to a mutation in the ATP7B transporter. Excessive amounts of copper accumulate in the body due to inhibition of the release of copper into bile. Because effective treatment is available, recognizing this disease in presymptomatic or early stages, when it can be reversed, is highly important. Diagnosis is often easy but the available tests (measurement of ceruloplasmin, and blood, urinary and liver copper levels) can be misleading. There is no single test with 100% sensitivity in screening nor do any of the tests, when used alone, provide 100% specificity. Diagnosis is currently based on the combination of clinical findings and the results of laboratory tests. Genetic study, with a finding of mutations in the two alleles of the ATP7B gene, is still not a rapid and easily available alternative and the absence of these mutations does not rule out the possible presence of other mutations not yet described.

Six pediatric patients with Niemann-Pick disease are reported. They have been studied at Hepatology Unit HI "La Paz" (Madrid) in the period of time between 1975-1988. They are one case of type A, one case of type B and four cases of type C. This group of pediatric patients serve us to make a revision of the disease attending to clinical and biochemical classification aspects, diagnosis and treatment. We insist on two aspects: 1) greater importance of enzymatic diagnose for the "Niemann-Pick complex", in view of the overlapping of clinical symptoms, 2) bone-marrow transplantation as therapeutic alternative and its indications.

Liver transplantation in children offers a therapeutic alternative for severe liver disease. Post-transplantation five-year survival reaches 76%. At the moment this technique must be indicated as a controversial subject, which requires considering both the severity of liver disease and scarcity of donors, with unpredictable waiting time. We report our experience after the study of 57 children selected for liver transplant. Their diagnosis, clinical and functional stage, situations considered as contraindications, and pre-transplantation management aimed at supporting candidates during waiting time and to diminish avoidable risks after surgery, is described. During waiting time, 15.9% of the patients died. Post-transplantation actuarial survival in our center is 63.6% (January 1986 to November 1988). Survival has markedly improved, reaching 81%, in the last 23 months in relation to a prophylactic approach of cytomegalovirus disease and performance of retransplantation in cases of severe graft dysfunction.

Eight children with chronic HBV hepatitis and glomerular disease were studied. There were seven males and one female, with ages between one and nine years old. Three had CPH and five CAH. All patients with CPH had membranous nephropathy, and those with CAH three had MNG. one membranoproliferative glomerulonephritis and one mesangial glomerulonephritis. Only six patients had moderate liver enlargement. In all, the diagnosis of HBV infection was performed by investigation of the etiology of their nephropathy. Liver function test showed signs of moderate necrobiosis with impaired biliary acid metabolism. All were HBsAg (+), antiHBc (+), six were antiHBe (+) and two were HBeAg (+). In one case renal deposit of HBsAg was found. Due to the frequent association of HBsAg and glomerulonephritis (GN) in children, an investigation of liver function is highly recommended in those patients with GN a HBV infection.

A two months old male affected by alpha-1-AT PiZZ deficiency with severe transient neonatal cholestasis is presented. Two hepatic biopsies were practiced in neonatal period. There was no evidence of PAS positive globules, but an intense univacuolar steatosis and a rossetoid transformation of hepatocytes were observed. Both findings are identical to those found in the histopathologic study of the liver in certain metabolic diseases such as fructosemia and galactosemia. A third biopsy practiced at an age of two years confirmed diagnosis of alpha-1-AT deficit since presence of PAS positive globules was established. It must be pointed out that histopathological findings show great variability among different patients with alpha-1-AT deficit in the neonatal period, as well as the infrequent presence of PAS positive globules in hepatic biopsies of those c during the first months of life.