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JPGN Reports May 2024Herbal and dietary supplements (HDS) are a common etiology of drug induced liver injury and, specifically, Herbalife® supplements have been implicated. Hepatitis...
Herbal and dietary supplements (HDS) are a common etiology of drug induced liver injury and, specifically, Herbalife® supplements have been implicated. Hepatitis associated aplastic anemia (HAAA) is a rare and potentially fatal complication after acute hepatitis characterized by pancytopenia. While there have been rare cases of HDS leading to HAAA, no cases of Herbalife® induced liver injury leading to HAAA have been reported from this specific HDS. We report a unique case of severe aplastic anemia developing after sub-fulminant liver failure associated with chronic HDS use. This case illustrates the importance of warning the public about HDS as their use continues to increase. It is not only important to recognize HDS as etiology, but also for healthcare providers to carefully monitor these patients after resolution of liver injury for the development of HAAA.
PubMed: 38756121
DOI: 10.1002/jpr3.12041 -
World Journal of Pediatric Surgery 2024In recent years, Mendelian randomization (MR) has been widely used to infer causality of related disease risk exposures. However, this strategy has not been applied to...
BACKGROUND
In recent years, Mendelian randomization (MR) has been widely used to infer causality of related disease risk exposures. However, this strategy has not been applied to biliary atresia (BA).
METHODS
Genome-wide association studies (GWAS) data of 41 inflammatory cytokines, 731 immune cell traits, and 1400 metabolites were obtained from public databases as exposure factors. The outcome information was obtained from a GWAS meta-analysis of 499 children with BA and 1928 normal controls. Inverse variance weighting was the primary causality analysis. Cochran Q-test, MR-Egger intercept, MR pleiotropy residual sum and outlier, and 'leave-one-out' analyses were used for sensitivity analysis. Reverse MR, MR-Steiger, and Linkage Disequilibrium Score were used to exclude the effects of reverse causality, genetic association, and linkage disequilibrium.
RESULTS
MR results showed that a total of seven traits had potential causal relationships with BA, including three inflammatory cytokines: eotaxin (odds ratio (OR)=1.45, 95% confidence interval (CI): 1.08 to 1.95, =0.18), G-CSF (OR=4.21, 95% CI: 1.75 to 10.13, =0.05) and MCP-1/MCAF (OR=1.53, 95% CI: 1.12 to 2.10, =0.14); three immune cell traits: CD8dim NKT/T cells ratio (OR=0.59, 95% CI: 0.45 to 0.77, =0.06), CD8dim NKT counts (OR=0.58, 95% CI: 0.43 to 0.78, =0.06), CD8dim NKT/lymphocyte ratio (OR=0.63, 95% CI: 0.49 to 0.81, =0.06); one metabolite: X-12261 levels (OR=2.86, 95% CI: 1.73 to 4.74, =0.06).
CONCLUSIONS
In this study, eotaxin, G-CSF, MCP-1/MCAF, and X-12261 levels were shown to be risk factors for BA. However, CD8dim NKT/T cells ratio, CD8dim NKT counts, and CD8dim NKT/lymphocyte ratio were protective factors for BA. These findings provided a promising genetic basis for the etiology, diagnosis, and treatment of BA.
PubMed: 38737962
DOI: 10.1136/wjps-2023-000754 -
Developmental Biology May 2024Impaired formation of the biliary network can lead to congenital cholestatic liver diseases; however, the genes responsible for proper biliary system formation and...
Impaired formation of the biliary network can lead to congenital cholestatic liver diseases; however, the genes responsible for proper biliary system formation and maintenance have not been fully identified. Combining computational network structure analysis algorithms with a zebrafish forward genetic screen, we identified 24 new zebrafish mutants that display impaired intrahepatic biliary network formation. Complementation tests suggested these 24 mutations affect 24 different genes. We applied unsupervised clustering algorithms to unbiasedly classify the recovered mutants into three classes. Further computational analysis revealed that each of the recovered mutations in these three classes has a unique phenotype on node-subtype composition and distribution within the intrahepatic biliary network. In addition, we found most of the recovered mutations are viable. In those mutant fish, which are already good animal models to study chronic cholestatic liver diseases, the biliary network phenotypes persist into adulthood. Altogether, this study provides unique genetic and computational toolsets that advance our understanding of the molecular pathways leading to biliary system malformation and cholestatic liver diseases.
PubMed: 38729406
DOI: 10.1016/j.ydbio.2024.05.005 -
International Journal of Surgery Case... Apr 2024Paraduodenal hernias are difficult to diagnose due to their unusual presentation. Herein, five new cases are added to the literature.
INTRODUCTION AND IMPORTANCE
Paraduodenal hernias are difficult to diagnose due to their unusual presentation. Herein, five new cases are added to the literature.
CASE PRESENTATION
Four male and one female child complained of paraduodenal hernias, two on the right side and three on the left side. The intestinal part that herniated inside the hernia sac was also malrotated in four patients. One patient had Meckel's diverticulum with a herniated intestine. One infant had extrahepatic biliary disease, a single atrium, polysplenia, intestinal malrotation, and a left paraduodenal hernia. Exploratory labarotomy was done for reduction of the intestine, reorientation, and repair of hernia orifices.
CLINICAL DISCUSSION
Paraduodenal hernia is a component of malrotation. Cautious dissection of the hernia orifice is required to keep away from injuries to the inferior mesenteric vein or left colic artery in the course of the restoration of the left paraduodenal hernia. Also, the superior mesenteric vessels may be injured in the course of the restoration of the right paraduodenal hernia.
CONCLUSION
There is a correlation between the occurrence of PDH with malrotation. The diagnosis of malrotation can be made with an ultrasound abdomen; however, it is true that ultrasound cannot make a confirmed diagnosis in all patients. Once the diagnosis of a mesocolic hernia has occurred, surgical repair is mandatory by closure of the defect.
PubMed: 38714067
DOI: 10.1016/j.ijscr.2024.109696 -
EJIFCC Apr 2024Early detection of biliary atresia is crucial for timely intervention and improved outcomes in infants with elevated conjugated bilirubin levels. This study aims to...
Early detection of biliary atresia is crucial for timely intervention and improved outcomes in infants with elevated conjugated bilirubin levels. This study aims to investigate the viability of cord blood gas analysis as a novel method for assessing conjugated bilirubin levels. Infants with high heel stick levels also showed elevated cord blood bilirubin levels, indicating that cord blood testing could replace the need for repeat heel stick tests, especially benefiting low birth weight infants. Ongoing research, including larger cohorts and alternative bilirubin measurement methods, will further validate this innovative screening approach. Infants with biliary atresia have high conjugated bilirubin levels at birth. As a result, infants can be screened with newborn conjugated bilirubin measurements, to allow for early detection, timely treatment, and the best chances of delaying or even avoiding the need for a liver transplant [1]. An important limitation of screening, however, is that infants must undergo a separate blood test. To overcome this limitation, we investigated whether conjugated bilirubin measurements from cord blood could be useful.
PubMed: 38706735
DOI: No ID Found -
EBioMedicine May 2024Biliary atresia (BA) is a neonatal fibro-inflammatory cholangiopathy with ductular reaction as a key pathogenic feature predicting poor survival. Mucosal-associated...
BACKGROUND
Biliary atresia (BA) is a neonatal fibro-inflammatory cholangiopathy with ductular reaction as a key pathogenic feature predicting poor survival. Mucosal-associated invariant T (MAIT) cells are enriched in human liver and display multiple roles in liver diseases. We aimed to investigate the function of MAIT cells in BA.
METHODS
First, we analyzed correlations between liver MAIT cell and clinical parameters (survival, alanine transaminase, bilirubin, histological inflammation and fibrosis) in two public cohorts of patients with BA (US and China). Kaplan-Meier survival analysis and spearman correlation analysis were employed for survival data and other clinical parameters, respectively. Next, we obtained liver samples or peripheral blood from BA and control patients for bulk RNA sequencing, flow cytometry analysis, immunostaning and functional experiments of MAIT cells. Finally, we established two in vitro co-culture systems, one is the rhesus rotavirus (RRV) infected co-culture system to model immune dysfunction of human BA which was validated by single cell RNA sequencing and the other is a multicellular system composed of biliary organoids, LX-2 and MAIT cells to evaluate the role of MAIT cells on ductular reaction.
FINDINGS
Liver MAIT cells in BA were positively associated with low survival and ductular reaction. Moreover, liver MAIT cells were activated, exhibited a wound healing signature and highly expressed growth factor Amphiregulin (AREG) in a T cell receptor (TCR)-dependent manner. Antagonism of AREG abrogated the proliferative effect of BA MAIT cells on both cholangiocytes and biliary organoids. A RRV infected co-culture system, recapitulated immune dysfunction of human BA, disclosed that RRV-primed MAIT cells promoted cholangiocyte proliferation via AREG, and further induced inflammation and fibrosis in the multicellular system.
INTERPRETATION
MAIT cells exhibit a wound healing signature depending on TCR signaling and promote ductular reaction via AREG, which is associated with advanced fibrosis and predictive of low survival in BA.
FUNDING
This work was funded by National Natural Science Foundation of China grant (82001589 and 92168108), National Key R&D Program of China (2023YFA1801600) and by Basic and Applied Basic Research Foundation of Guangdong (2020A1515110921).
Topics: Humans; Biliary Atresia; Amphiregulin; Mucosal-Associated Invariant T Cells; Male; Female; Liver; Coculture Techniques; Bile Ducts; Biomarkers; Infant
PubMed: 38678809
DOI: 10.1016/j.ebiom.2024.105138 -
Frontiers in Pediatrics 2024Inborn errors of bile acid metabolism (IEBAM) cause cholestasis during the neonatal period, and 8 types of IEBAM have been reported to date. IEBAM accounts for...
Inborn errors of bile acid metabolism (IEBAM) cause cholestasis during the neonatal period, and 8 types of IEBAM have been reported to date. IEBAM accounts for approximately 2% of cases of cholestasis of unknown cause. As only 10 patients have been identified in Japan, IEBAM presents diagnostic challenges due to the similarity of clinical symptoms with biliary atresia, thus necessitating precise differentiation to avoid unnecessary invasive procedures. Laboratory tests in IEBAM are characterized by normal -glutamyltransferase (GGT) and serum total bile acid (STBA) levels despite the presence of cholestasis; therefore, measuring STBA and GGT is essential to distinguishing biliary atresia from IEBAM. With suspected IEBAM, liquid chromatography-mass spectrometry (LC/MS) analysis of urinary bile acids is needed to optimize diagnostic and therapeutic efficacy and avoid open cholangiography and initiate treatment for primary bile acids such as cholic acid or chenodeoxycholic acid. This prospective report aims to increase awareness of IEBAM by highlighting the characteristics of general blood test and bile acid profiles from LC/MS analyses of blood, urine, and stool samples.
PubMed: 38646510
DOI: 10.3389/fped.2024.1385970 -
Radiology Case Reports Jun 2024Serious iatrogenic vascular injuries are considered uncommon; however, they are underreported. There are limited studies discussing the proper management of these...
Serious iatrogenic vascular injuries are considered uncommon; however, they are underreported. There are limited studies discussing the proper management of these injuries; therefore, the management is often anecdotal. A 4-month-old female patient presented with elevated liver enzymes and cholecystitis with sludge. Her HIDA scan suggested biliary atresia. During the surgery, there was a bilateral iatrogenic injury to the hepato-duodenal ligament, including the portal vein, hepatic artery, and bile ducts. The patient underwent splenectomy and cholecystectomy, and the hepatic artery transection was successfully managed with a splenic artery jump graft and a portal vein bypass initiated with the SMV using a Gore-Tex vascular graft. The management of iatrogenic vascular injury depends primarily on the assessment of the stage of the injury, which should be conducted by experienced surgeons using proper strategies in an established hepato-biliary surgical center. Additionally, there is little data provided in the literature, mostly case reports. Therefore, no preferred or specific approach can be found.
PubMed: 38645539
DOI: 10.1016/j.radcr.2024.02.037 -
Autopsy & Case Reports 2024Biliary atresia (BA) is a fibro-obliterative cholestatic disease of infancy. The presence of cartilage in the resected tissue is an uncommon finding. We documented the...
Biliary atresia (BA) is a fibro-obliterative cholestatic disease of infancy. The presence of cartilage in the resected tissue is an uncommon finding. We documented the presence of both mature and immature hyaline cartilage in the portal plate and the wall of the gallbladder in a 2-month-old girl infant with BA who had undergone Kasai portoenterostomy. The presence of cartilage could be part of a heterotopia or an uncommon connective tissue metaplasia. The presence of immature cartilage with the merging of the perichondrium with the soft tissue highlights a metaplastic etiology in the index case.
PubMed: 38628285
DOI: 10.4322/acr.2024.481 -
Clinical and Experimental Pediatrics Apr 2024Bacterial bloodstream infections (BSI) are the leading cause of mortality and morbidity in pediatric solid organ transplant recipients. This systematic review aimed to...
Bacterial bloodstream infections (BSI) are the leading cause of mortality and morbidity in pediatric solid organ transplant recipients. This systematic review aimed to pool global data from leading transplant institutions and identify the overall incidence, risk factors, and causative organisms of BSI in pediatric liver transplant recipients. A systematic review of the PubMed and OVID databases was conducted from 2000 to 2022. The initial search yielded 252 unique articles, which were independently reviewed by 2 authors. Articles that reported pediatric-specific data on BSI in isolated liver transplant patients were included, including the incidence of BSI, isolated organisms, and involved risk factors involved. This systematic review was registered with PROSPERO (ID: CRD42023403206). Fourteen articles from the United States, France, Iran, Japan, Korea, South Africa, Thailand, and Turkey were included. A total of 4,812 liver transplants were included in the final analysis. The mean patient age was 25 months (age range, 0-18 years), and 50.9% were male. The overall incidence of BSI was 23.5% (range, 14.7%-55%). The most commonly reported organisms were Staphylococcus epidermidis, Enterococcus, Klebsiella spp., and Escherichia coli. Among the risk factors studied, postoperative biliary complications, a medical history of biliary atresia, and younger age were the risk factors most commonly associated with BSI. Bacterial BSI after pediatric liver transplantation occur at a high incidence, with a unique organism profile notable for a higher percentage of gram-negative organisms. Further studies are required to determine the most appropriate prophylactic and empirical antibiotic management strategies for this population.
PubMed: 38605664
DOI: 10.3345/cep.2023.01466