Broadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease.

Complement hyperactivation, angiopathic thrombosis and protein-losing enteropathy (CHAPLE disease) is a lethal disease caused by genetic loss of the complement regulatory protein CD55, leading to overactivation of complement and innate immunity together with immunodeficiency due to immunoglobulin wasting in the intestine. We report in vivo human data accumulated using the complement C5 inhibitor eculizumab for the medical treatment of patients with CHAPLE disease. We observed cessation of gastrointestinal pathology together with restoration of normal immunity and metabolism. We found that patients rapidly renormalized immunoglobulin concentrations and other serum proteins as revealed by aptamer profiling, re-established a healthy gut microbiome, discontinued immunoglobulin replacement and other treatments and exhibited catch-up growth. Thus, we show that blockade of C5 by eculizumab effectively re-establishes regulation of the innate immune complement system to substantially reduce the pathophysiological manifestations of CD55 deficiency in humans.

Isolation, identification, and in vitro probiotic characterization of forty novel Bifidobacterium strains from neonatal feces in Erzurum province, Türkiye.

BACKGROUND: Neonatal feces are one of the most important sources for probiotic isolation. The purpose of this study was the isolation and identification of Bifidobacterium spp. from neonatal feces and the evaluation of in vitro probiotic properties of strains including safety tests. RESULTS: A total of 40 isolates were obtained from 14 healthy newborns' feces in Erzurum province, Türkiye. By their rep-PCR patterns and 16S rRNA gene sequences, isolates were identified as 26 Bifidobacterium breve and 14 Bifidobacterium longum. Fifteen of the isolates tolerated bile salts and showed high resistance to simulated gastric juice. Isolates exhibited varying rates of auto-aggregation and hydrophobicity. In addition, most of the isolates displayed antibacterial activity against Escherichia coli O157:H7, Staphylococcus aureus ATCC 29213, Salmonella Typhimurium RSHMB 95091, and Pseudomonas aeruginosa ATCC 9027. However, only one strain showed bile salt hydrolase activity and two strains showed the ability to produce H2O2. Bifidobacterium strains were generally sensitive to the tested antibiotics and lacked kanamycin, gentamicin, and streptomycin resistance genes, and hemolytic and DNAse activities. On the other hand, it was determined that five strains had various virulence genes including gelE, esp, efaAfs, hyl, and ace. CONCLUSION: Results of the present study suggested that B. longum BH28, B. breve BH4 and B. breve BH5 strains have the potential as probiotic candidates for further studies. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Altered von Willebrand Factor and ADAMTS13 Levels in Children With Cirrhosis and Extrahepatic Portal Hypertension.

BACKGROUND/AIM: This study was concerned with whether vWF (von Willebrand factor) and a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS13) has altered in patients with cirrhosis and extrahepatic portal hypertension (EPH). We aimed to investigate changes to vWF and ADAMTS13 in children with cirrhosis and EPH. PATIENTS AND METHODS: This study was conducted between January and October 2019 with both cirrhosis and EPH patients and with healthy volunteers. The von Willebrand factor antigen (vWF:Ag), von Willebrand Ristocetin cofactor (vWF:RCo), and ADAMTS13 antigen and activity were studied. RESULTS: Twenty-eight children with cirrhosis, 16 children with EPH, and 20 healthy controls were included in the study. vWF:Ag and vWF:RCo levels were higher in patients with cirrhosis than in healthy controls (171.65±101.67 vs. 85.86±30.58, P<0.01 and 121.62±55.83 vs. 61.52±27.03, P<0.01, respectively). vWF:Ag and vWF:RCo levels were higher in patients with EPH than in healthy controls (133.93±80.13 vs. 85.86±30.58, P<0.01 and 103.18±58.55 vs. 61.52±27.03, P=0.02, respectively). The ADAMTS13 antigen and activity levels were lower in patients with cirrhosis than in healthy controls (0.58±0.23 vs. 0.97±0.15, P<0.01 and 49.91±22.43 vs. 86.51±22.07, P=0.02, respectively). The ADAMTS13 antigen and activity levels were lower in patients with EPH than in healthy controls (0.69±0.11 vs. 0.97±0.15, P=0.03; and 68.50±13.29 vs. 86.51±22.07, P=0.02, respectively). The increase in vWF and the decrease in ADAMTS13 were more pronounced in cirrhotic patients with autoimmune hepatitis (AIH) than in non-AIH patients. CONCLUSIONS: While levels of vWF:Ag and vWF:RCo increased in children with cirrhosis and EPH, levels of the ADAMTS13 antigen and ADAMTS13 activity decreased. These alterations were more pronounced in patients with AIH-derived cirrhosis.

A Novel Mutation of ATP7B Gene in a Case of Wilson Disease.

Wilson disease (WD) (OMIM# 277900) is an autosomal recessive inherited disorder characterized by excess copper (Cu) storage in different human tissues, such as the brain, liver, and the corneas of the eyes. It is a rare disorder that occurs in approximately 1 in 30,000 individuals. The clinical presentations of WD are highly varied, primarily consisting of hepatic and neurological conditions. WD is caused by homozygous or compound heterozygous mutations in the ATP7B gene. The diagnosis of the disease is complicated because of its heterogeneous phenotypes. The molecular genetic analysis encourages early diagnosis, treatment, and the opportunity to screen individuals at risk in the family. In this paper, we reported a case with a novel, hotspot-located mutation in WD. We have suggested that this mutation in the ATP7B gene might contribute to liver findings, progressing to liver failure with a loss of function effect. Besides this, if patients have liver symptoms in childhood and/or are children of consanguineous parents, WD should be considered during the evaluation of the patients.

The Frequency of Lysosomal Acid Lipase Deficiency in Children With Unexplained Liver Disease.

OBJECTIVES: Evidence suggests that lysosomal acid lipase deficiency (LAL-D) is often underdiagnosed because symptoms may be nonspecific. We aimed to investigate the prevalence of LAL-D in children with unexplained liver disease and to identify demographic and clinical features with a prospective, multicenter, cross-sectional study. METHODS: Patients (aged 3 months-18 years) who had unexplained transaminase elevation, unexplained hepatomegaly or hepatosplenomegaly, obesity-unrelated liver steatosis, biopsy-proven cryptogenic fibrosis and cirrhosis, or liver transplantation for cryptogenic cirrhosis were enrolled. A Web-based electronic data collection system was used. LAL activity (nmol/punch/h) was measured using the dried blood spot method and classified as LAL-D (<0.02), intermediate (0.02-0.37) or normal (> 0.37). A second dried blood spot sample was obtained from patients with intermediate LAL activity for confirmation of the result. RESULTS: A total of 810 children (median age 5.6 years) from 795 families were enrolled. The reasons for enrollment were unexplained transaminase elevation (62%), unexplained organomegaly (45%), obesity-unrelated liver steatosis (26%), cryptogenic fibrosis and cirrhosis (6%), and liver transplantation for cryptogenic cirrhosis (<1%). LAL activity was normal in 634 (78%) and intermediate in 174 (21%) patients. LAL-D was identified in 2 siblings aged 15 and 6 years born to unrelated parents. Dyslipidemia, liver steatosis, and mild increase in aminotransferases were common features in these patients. Moreover, the 15-year-old patient showed growth failure and microvesicular steatosis, portal inflammation, and bridging fibrosis in the liver biopsy. Based on 795 families, 2 siblings in the same family were identified as LAL-D cases, making the prevalence of LAL-D in this study population, 0.1% (0.125%-0.606%). In the repeated measurement (76/174), LAL activity remained at the intermediate level in 38 patients. CONCLUSIONS: Overall, the frequency of LAL-D patients in this study (0.1%) suggests that LAL-D seems to be rare even in the selected high-risk population.

The Liver Fat Fraction and Abdominal Subcutaneous and Visceral Fat Volume Distribution in Normal-Weight, Overweight, and Obese Children Using a New Magnetic Resonance Imaging Technique.

OBJECTIVES: The purpose of this study was to evaluate liver fat fraction and subcutaneous and visceral fat volumes using new magnetic resonance imaging in normal-weight, overweight, and obese children. METHODS: Patients at below the 85th percentile of body mass index (BMI) z score (5/25 patients) were assigned to the normal-weight group; patients between 85th and 95th percentile of BMI z score (9/25 patients) were assigned to the overweight group, and patients above the 95th percentile of BMI z score (11/25 patients) were assigned to the obese group. Liver fat fraction and subcutaneous and visceral fat volumes were measured on 3-dimensional volume measurement workstation. RESULTS: Liver fat fraction and subcutaneous fat volume had weak correlation (r = 0.18, P = 0.411). Liver fat fraction and visceral fat volume revealed weak correlation (r = 0.25, P = 0.672); visceral and subcutaneous fat volume demonstrated strong correlation (r = 0.67, P = 0.047). CONCLUSIONS: There is strong correlation between subcutaneous fat volume and visceral fat volume in overweight and obese children.

Percutaneous endoscopic gastrostomy in children: Is early feeding safe?

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is the preferred method to provide nutritional support for patients with normal gastrointestinal function but cannot be fed orally for a variety of reasons. Owing to safety concerns, the first feeding after PEG tube placement is generally delayed. Early feeding may be an option; however, childhood studies regarding early feeding after the PEG procedure are highly insufficient. METHODS: A prospective randomized controlled study was conducted to compare early (4th hour) and late (12th hour) feeding after the PEG procedure. The PEG process was performed with the standard pull technique. Prophylactic antimicrobial drugs were not used. Complications such as gastric residue after feeding, vomiting, fever, systemic signs of infection, and duration of hospital stay were recorded. Tube feeding training was given to parents during their stay in the hospital in both groups. In the first and third days following PEG, the patients were visited by an experienced nurse in their homes and evaluated in terms of potential complications. RESULTS: The study was completed with a total of 69 patients: 35 in the early feeding group and 34 in the late feeding group. The demographic characteristics of the groups were similar. Vomiting was rare and detected as similar in both groups (early feeding group 8.5% [3/35], late feeding group 8.8% [3/34], P = 1.00). Rarely, minor gastric residue was observed in both groups (early feeding group 11.4%, late feeding group 8.8% [P = 1.00]). The amount of gastric residue in the early feeding group was a maximum of 13.2 mL, whereas the late feeding group had a maximum of 14.3 mL. The average duration of stay in the hospital for the early and late feeding groups was calculated as 6.7 ± 0.64 and 28.3 ± 3.74 hours, respectively (P < 0.001). Leakage from gastrostomy fistulas, peritonitis, and aspiration were not observed in any patients. CONCLUSIONS: The feeding at the fourth hour after PEG placement was safe and well tolerated by patients and shortened the duration of the hospital stay. The use of prophylactic antibiotics seems to be unnecessary before the procedure.

Extremely rare cause of congenital diarrhea: enteric anendocrinosis.

Congenital diarrheal disorders consist of a variety of chronic enteropathies. There are approximately 30 different diseases that can be classified into four groups according to the mechanisms involved in pathogenesis: (i) absorption and transport of nutrients and electrolytes; (ii) enterocyte differentiation and polarization; (iii) enteroendocrine cell differentiation; and (iv) modulation of the intestinal immune response. Affected patients often present with life-threatening diarrhea, in the first few weeks of life. A new disorder, enteric anendocrinosis, which is characterized by severe malabsorptive diarrhea and a lack of intestinal enteroendocrine cells has recently been described in six patients with recessively inherited mutations in the Neurogenin-3 gene. In this report we describe a seventh case with a review of the literature.

Seronegative autoimmune hepatitis in childhood.

Comprehensive guidelines on seropositive autoimmune hepatitis have been published for both adults and children, although these guidelines comprise only limited knowledge about seronegative autoimmune hepatitis. Autoimmune hepatitis presents as an acute or chronic progressive disease and poor outcomes are inevitable if left untreated. The absence of autoantibody positivity, hypergammaglobulinemia and lack of comprehensive algorithms makes seronegative autoimmune hepatitis a mysterious disease. In general, seronegative autoimmune hepatitis often presents with acute hepatitis, and its treatment and prognosis similar to seropositive autoimmune hepatitis. The present review focuses on the known characteristics of seronegative autoimmune hepatitis in childhood, and those of which current knowledge is vague.

Biliary atresia and congenital disorders of the extrahepatic bile ducts.

Biliary atresia (BA) and choledochal cysts are diseases of the intrahepatic and extrahepatic biliary tree. While their exact etiopathogeneses are not known, they should be treated promptly due to the potential for irreversible parenchymal liver disease. A diagnosis of BA may be easy or complicated, but should not be delayed. BA is always treated surgically, and performing the surgery before the age of 2 mo greatly increases its effectiveness and extends the time until the need for liver transplantation arises. While the more common types of choledochal cysts require surgical treatment, some can be treated with endoscopic retrograde cholangiopancreatography. Choledochal cysts may cause recurrent cholangitis and the potential for malignancy should not be ignored.

Clinical Features of Children with COVID-19 Infection: Single-Center Experience.

OBJECTIVE: Compared to adult studies, there are few epidemiological and clinical reports on coronavirus disease 2019 in children. We aimed to present the demographic, epidemiological, and clinical findings of hospitalized pediatric coronavirus disease 2019 patients. MATERIALS AND METHODS: Patients aged 0-18 years who were hospitalized between March and July 2020 due to severe acute respiratory syndrome coronavirus 2 infection were evaluated retrospectively. RESULTS: The mean age was 90.2 ± 67.5 (7-24) months and 23 (51%) were female. Clinical presentation was asymptomatic in 15 cases (33.3%), mild/moderate in 26 cases (57.8%), and severe/critical in 4 cases (8.9%). Three (6.6%) of the patients had chronic medical conditions that placed them in the high-risk group for coronavirus disease 2019. The source of infection was household transmission in 29 cases (64.4%). The most common symptoms were cough, fever, and fatigue. Mean serum lactate, C-reactive protein (CRP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels were significantly higher in severe/criti- cal patients compared to the other two groups (P < .05). severe acute respiratory syndrome coronavirus 2 negativity in control swabs (n=26) occurred at a mean of 10.6 ± 2.9 days after symptom onset. Forty-three patients (95.6%) were followed in the ward and 2 (4.4%) were admitted to the intensive care unit. CONCLUSION: Children aged 0-18 years constituted a very small proportion of coronavirus disease 2019 reverse transcription-polymerase chain reaction -positive cases. Asymptomatic carriage of SARS- CoV-2 by a large proportion of children seems to be a major factor driving community spread. Some children with coronavirus disease 2019 may also present neurological findings. coronavirus disease 2019 infection is more severe in patients with comorbidities, and support therapy is important in these patients.

Probability of urinary tract infection in infants with ureteropelvic junction obstruction: is antibacterial prophylaxis really needed?

In infants with ureteropelvic junction obstruction (UPJO), the risk of urinary tract infection (UTI) is unknown, and there is a lack of prospective studies showing definitive evidence regarding the benefits and necessity of antibiotic prophylaxis. The aim of this study was to assess the risk of UTI in infants with UPJO and to determine whether the risk varies according to the degree of hydronephrosis. Infants with hydronephrosis detected prenatally or within the postnatal 28th day and who had no previous history of UTI were followed prospectively without antibacterial prophylaxis. Imaging studies were performed according to our Pediatric Uro-Nephrology Study Group protocol. Dimercaptosuccinate (DMSA) scintigraphy was performed in all infants at the end of 1 year of follow-up. Eighty-four infants (56 boys, 28 girls) were included in the study. The distribution of patients in each hydronephrosis grading group was incidentally similar. Within a median follow-up period of 18 (12-24) months, none of the patients had UTI. Furthermore, no pyelonephritic scar was found on DMSA scans in any patient. We conclude that prophylactic antibiotic usage is not indicated in infants with UPJO, regardless of the severity of hydronephrosis, as the risk of UTI is minimal in this population.

Acute-on-chronic liver failure in children.

Although various complex definitions of acute-on-chronic liver failure (ACLF) have been suggested in relation to adult patients, there is currently no universal definition of the syndrome in pediatric patients. In simplified terms, ACLF is characterized by the acute deterioration of the liver functions due to the effects of a precipitating factor on the basis of a chronic liver disease. Acute events and underlying liver diseases are very different in children from those seen in adults. Moreover, acute events and underlying chronic liver diseases vary among geographical regions, although it seems that the most common such diseases and acute events are autoimmune hepatitis, Wilson's disease, and their flares. ACLF is associated with a poor prognosis. While no scoring systems have been developed to predict the prognosis for children with ACLF, modified versions of the Asian Pacific Association for the Study of the liver's acute-on-chronic liver failure scoring system and the Chronic Liver Failure-Sequential Organ Failure Assessment criteria can be used in children until specific and validated scoring systems are available. Aside from liver transplantation, there is no proven treatment for ACLF. Thus, the early recognition of ACLF prior to the development of extrahepatic organ failure is important.

Acute-on-Chronic Liver Failure in Children: A Single-Center Experience.

OBJECTIVES: Acute-on-chronic liver failure and its outcomes have not yet been evaluated in detail in children. We aimed to evaluate the etiology, acute events, and prognostic factors of acute-on-chronic liver failure in children. MATERIALS AND METHODS: Pediatric patients (age 2-18 years) diagnosed with acute-on-chronic liver failure between April 2014 and April 2020 were evaluated retrospectively. Acute-on-chronic liver failure was defined as the presence of acute hepatic insult in previously diagnosed or undiagnosed chronic liver disease causing jaundice (total serum bilirubin ≥5 mg/dL) and coagulopathy (international normalized ratio of ≥2.0) and clinical and/or radiological ascites and/or hepatic encephalopathy within 4 weeks. Acute-on-Chronic Liver Failure Research Consortium and Chronic Liver Failure-Sequential Organ Failure Assessment scores were calculated for patients at first admission and at end of day 5 or before liver transplant. RESULTS: Our study included 29 patients. Underlying chronic liver diseases were mostly autoimmune hepatitis (51.72%) and Wilson disease (27.58%), with flare-ups of these diseases also the most common acute events (48.28% and 27.58%, respectively). Seven patients (24.14%) received liver transplants. At first admission, Acute-on-Chronic Liver Failure Research Consortium and Chronic Liver Failure-Sequential Organ Failure Assessment cut-off scores to predict liver transplant were 7.5 and 6.5; at end of day 5 or before transplant, cut-off scores were 8.5 and 7.5, respectively. The 8.5 cut-off score on day 5 was the most specific and sensitive to predict liver transplant. International normalized ratio cut-off of 3.04 predicted transplant requirement with maximum sensitivity and specificity. CONCLUSIONS: Wilson disease and autoimmune hepatitis were the most common underlying chronic and acute events of acute-on-chronic liver failure in children. Although an Acute-on-Chronic Liver Failure Research Consortium score ≥ 8.5 best predicted liver transplant, for patients with scores ≥ 7.5 and being followed in a nontransplant center, patient referral to a transplant center is appropriate.

Analysis of correlation between liver fat fraction and AST and ALT levels in overweight and obese children by using new magnetic resonance imaging technique.

BACKGROUND/AIMS: Proton density fat fraction (PDFF) magnetic resonance (MR) imaging can be a useful technique for volumetric measurements of liver fat. The purpose of our study was to evaluate the correlation between liver fat fraction (LFF) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in children who are overweight and obese. MATERIALS AND METHODS: Overall, 25 children, aged 9-17 years, were included. Patients with a body mass index (BMI) z-score between 85-95th percentile (12 of 25 patients) were assigned to the overweight group, and those with BMI z-score above 95th percentile (13 of 25 patients) were assigned to the obese group. The control group comprised 12 healthy children with BMI z-score below 85th percentile. Liver fat fraction measurements were performed on 3D volume measurement workstation by using PDFF magnetic resonance (MR) images. Spearman's correlation coefficients between liver fat fraction and AST and ALT levels were evaluated individually for overweight, obese, and control groups. Receiver operator characteristics (ROC) analysis was also performed. RESULTS: In the overweight and obese groups, the liver proton density fat fraction and AST levels had a strong correlation (r=0.716, p<0.001). In addition, the LFF and ALT levels demonstrated a strong correlation (r=0.878, p<0.001). ROC analysis ascertained an optimal liver fat fraction threshold of 114 for predicting AST level (sensitivity=75%, specificity=89%). ROC analysis ascertained an optimal LFF threshold of 114 for predicting ALT level (sensitivity=80%, specificity=90%). CONCLUSION: Our results indicate a strong correlation between LFF values and AST and ALT levels in children who are overweight and obese.

Liver Involvement in Children with Alpha-1 Antitrypsin Deficiency: A Multicenter Study.

PURPOSE: Alpha-1 antitrypsin deficiency (A1ATD) in one of the most common genetic causes of liver disease in children. We aimed to analyze the clinical characteristics and outcomes of patients with A1ATD. METHODS: This study included patients with A1ATD from five pediatric hepatology units. Demographics, clinical findings, genetics, and outcome of the patients were recorded (n=25). RESULTS: Eight patients (32.0%) had homozygous PiZZ genotype while 17 (68.0%) had heterozygous genotype. Patients with PiZZ genotype had lower alpha-1 antitrypsin levels than patients with PiMZ genotype (37.6±7.7 mg/dL vs. 66.5±22.7 mg/dL, p=0.0001). Patients with PiZZ genotype were diagnosed earlier than patients with PiMZ genotype, but this was not significant (13±6.8 months vs. 23.7±30.1 months, p=0.192). Follow-up revealed the death of one patient (12.5%) with a homozygous mutation, and revealed that one patient had child A cirrhosis, five patients (62.5%) had chronic hepatitis, and one patient (12.5%) was asymptomatic. Nine of the 17 patients with a heterozygous mutation had chronic hepatitis (52.9%), two (11.7%) had child A cirrhosis, and six (35.2%) were asymptomatic. Overall, 18 (72%) of the 25 children had liver pathology in the long-term. CONCLUSION: Although prevalence is rare, patients with liver disorders should be checked for alpha-1 antitrypsin levels. Moreover, long-term follow-up is essential because most patients have a liver pathology.