Gestational Alloimmune Liver Disease Research Articles

Clinical characteristics and outcomes of acute liver failure in neonates: a retrospective cohort in China.

Neonatal acute liver failure (NALF), as a rare disease with high mortality, has limited relevant literature reports in China. We attempted to analyze a NALF cohort to improve the prognosis of this disease. We included all patients diagnosed with NALF at our institution between 2016 and 2021 and retrospectively reviewed their electronic records. NALF was defined as an INR ≥ 2.0 due to liver disease 28days after birth. Comparisons were made according to etiology and outcome. The Kaplan-Meier method was used to estimate survival. Fifty-eight patients were included in this study. Etiologies included hypoxic/ischemic injury (29.3%), infection (27.6%), gestational alloimmune liver disease with neonatal hemochromatosis (GALD-NH) (10.3%), inherited metabolic diseases (5.2%), hemophagocytic lymphohistiocytosis (1.7%), other etiologies (12.1%), and unidentified causes (13.8%). Enteroviruses constituted 87.5% of the viral infections, whereas herpes simplex virus accounted for no infections. The median INR was significantly lower in the infection group than in the GALD-NH group (P < 0.05 for multiple comparisons). At the last follow-up, none of the patients had undergone liver transplantation, and the overall mortality rate was 50%. Liver function completely recovered in 31% of the patients, all of whom survived. The overall median survival time was 48days; 26days for hypoxic/ischemic injury and 43days for GALD-NH. The incidence of cholestasis was significantly greater among surviving patients (P = 0.018). Conclusion: Hypoxic/ischemic injury and infection are the predominant etiologies of NALF in China. The overall prognosis of NALF is poor, but its short-term prognosis is determined by the etiology. What is Known: • Neonatal acute liver failure (NALF) is a rare disorder with limited cohort studies, especially in China. • Gestational alloimmune liver disease, viral infections (especially herpes simplex virus), metabolic diseases and ischemic insults are common etiologies of NALF, which are significantly different from other populations. • There are no reliable biochemical markers to predict the outcome of NALF. What is New: • In this first report on a Chinese NALF cohort, we demonstrate that hypoxic/ischemic injury and infection (excluding herpes simplex virus) are the predominant etiologies of NALF. • The overall prognosis of NALF is poor, and its etiology determines the short-term outcome.

Establishing Neonate-specific Prognostic Markers in Acute Liver Failure: Admission Alpha Fetoprotein and Novel nALF Scores Predict Patient Outcomes

ObjectivesTo develop neonate-specific prediction models for survival with native liver (SNL) in neonatal acute liver failure (ALF) and to determine if these prediction models have superior accuracy to existing models for older children with ALF. Study designA single-center, retrospective chart review was conducted on neonates ≤ 30 days of life between 2005 and 2022 with ALF (INR ≥ 2 or prothrombin time [PT] ≥ 20s and liver dysfunction). Statistical analysis included comparison of patients by outcome of SNL and generalized linear modeling to derive prediction models. The predictive accuracy of variables was evaluated by receiver operating characteristic (ROC) analysis and Kaplan-Meier survival analysis. Results51 patients met inclusion criteria. The most common causes of neonatal ALF included ischemia (22%), infection (20%), and gestational alloimmune liver disease (GALD) (16%). Overall SNL rate was 43% (n=22). AFP levels were higher in SNL patients (p=0.034) and differed more significantly by SNL status among non-GALD patients (n=21, p=0.001). An AFP < 4775 ng/mL had 75% sensitivity and 100% specificity to predict death or transplant in non-GALD patients with an area under the ROC curve (AUROC) of 0.81. A neonate-specific admission model (INR and ammonia) and peak model (PT and ammonia) also predicted SNL with good accuracy (AUROC = 0.73 and 0.82 respectively). ConclusionsWe identified neonate-specific prognostic variables for SNL in ALF. Findings from our study may help early risk stratification to guide medical decision-making and consideration for liver transplantation.

Congenital neonatal hemochromatosis with recurrent neonatal deaths - a diagnostic nightmare: A case report

Background: Neonatal hemochromatosis (NH) is a rare disorder and the most common cause of acuteliver failure in neonates. NH is characterized by severe hepatic injury and iron overload with highperinatal mortality and morbidity. There is a high risk of recurrence in subsequent pregnancies of womenwho have had a child with neonatal hemochromatosis.Case presentation: A 40-year-old para 13 with one living child and three previous cesarian scarspresented at ten weeks with a history of recurrent neonatal deaths. Her last infant death was at fourmonths after she delivered a baby via cesarian birth at 36 weeks. The infant developed severe jaundicewith reduced urine output. Laboratory investigations revealed deranged liver function tests with elevatedserum ferritin levels. The infant received repeated exchange transfusions, immunoglobulin, anddexoferamine. However, she succumbed at four months. Her management for the current pregnancyrequired close follow-up and she delivered at 37 weeks gestation to a live male infant who is faring well.Discussion: The cause of NH is not fully understood. Significant evidence indicates that most cases ofneonatal hemochromatosis result from fetal liver disease due to maternal-fetal alloimmunity, a conditiontermed gestational alloimmune liver disease (GALD). In GALD, these antibodies bind to fetal liverantigen and activate the terminal complement cascade, resulting in hepatocyte injury and death.Conclusion: NH is the most common cause of neonatal acute liver injury and should be considered in allcases of severe fetal liver injury as well as in cases of stillbirth, fetal demise, and early postnatal death.

Hunting for the elusive target antigen in gestational alloimmune liver disease (GALD).

The prevailing concept is that gestational alloimmune liver disease (GALD) is caused by maternal antibodies targeting a currently unknown antigen on the liver of the fetus. This leads to deposition of complement on the fetal hepatocytes and death of the fetal hepatocytes and extensive liver injury. In many cases, the newborn dies. In subsequent pregnancies early treatment of the woman with intravenous immunoglobulin can be instituted, and the prognosis for the fetus will be excellent. Without treatment the prognosis can be severe. Crucial improvements of diagnosis require identification of the target antigen. For this identification, this work was based on two hypotheses: 1. The GALD antigen is exclusively expressed in the fetal liver during normal fetal life in all pregnancies; 2. The GALD antigen is an alloantigen expressed in the fetal liver with the woman being homozygous for the minor allele and the father being, most frequently, homozygous for the major allele. We used three different experimental approaches to identify the liver target antigen of maternal antibodies from women who had given birth to a baby with the clinical GALD diagnosis: 1. Immunoprecipitation of antigens from either a human liver cell line or human fetal livers by immunoprecipitation with maternal antibodies followed by mass spectrometry analysis of captured antigens; 2. Construction of a cDNA expression library from human fetal liver mRNA and screening about 1.3 million recombinants in Escherichia coli using antibodies from mothers of babies diagnosed with GALD; 3. Exome/genome sequencing of DNA from 26 presumably unrelated women who had previously given birth to a child with GALD with husband controls and supplementary HLA typing. In conclusion, using the three experimental approaches we did not identify the GALD target antigen and the exome/genome sequencing results did not support the hypothesis that the GALD antigen is an alloantigen, but the results do not yield basis for excluding that the antigen is exclusively expressed during fetal life., which is the hypothesis we favor.

Therapeutic plasma exchange for neonatal hepatic failure

We report a case of therapeutic plasma exchange in a neonate with fulminant liver failure. A six-day old, 2800-gram baby was referred to our medical center for evaluation and treatment of fulminant hepatic failure. The working diagnosis at admission was gestational alloimmune liver disease, and therapeutic plasma exchange was proposed. A double volume plasma exchange was successfully performed, using the Spectra Optia apheresis system, primed with packed red blood cells. Access was obtained via a radial artery catheter and a peripheral intravenous line. On hospital D-14 a diagnosis of E3 deficiency was confirmed, and disease-specific therapy was started. Automated TPE using peripheral arterial and venous catheters may be safely performed in neonates, and should be considered in the treatment of a variety of disorders including neonatal fulminant hepatic failure.

Neonatal Hemochromatosis: Systematic Review of Prenatal Ultrasound Findings-Is There a Place for MRI in the Diagnostic Process?

Neonatal hemochromatosis (NH) is an uncommon, severe disorder that results in fetal loss or neonatal death due to liver failure. NH is currently regarded as the phenotypic expression of gestational alloimmune liver disease (GALD). The diagnosis of NH-GALD is rarely prenatally established. In addition to providing a systematic review of the prenatal features that are identifiable using ultrasound (US) and MRI, we suggest a prenatal diagnosis algorithm for use in suspected NH during the first affected pregnancy. From a total of 586 database entries identified in PubMed, Google Scholar, and ResearchGate, we selected 18 studies published from 1993 to 2021 that reported maternal medical and obstetric history, prenatal ultrasound findings, and postpartum outcomes. We investigated the ultrasound and MRI features of these studies, along with the outcome due to this condition. A total of 74 cases were identified. The main reported prenatal US finding was fetal growth restriction (FGR) (33%), followed by oligohydramnios (13%) and hydrops fetalis (13%), with 13% cases described as uneventful. Other rare prenatal findings were fetal anemia, ascites, and abnormal fetal liver and spleen. Most pregnancies ended with fetal/perinatal death or therapeutic interruption of pregnancy. Favorable evolution with treatment (ensanguine transfusion and intravenous immunoglobulin (IVIG)) was reported for only 7% of fetuses. Using T2-weighted MRI, fetal extrahepatic siderosis confirmed prenatally in two cases and postnatally in 11 cases. IVIG treatment throughout subsequent pregnancies was found to significantly improve fetal prognosis. MRI should be indicated in selected cases of oligohydramnios, fetal hydrops, fetal hepatomegaly, ascites, or unexplained FGR or anemia after ruling out all other more frequently encountered conditions. MRI can be used to detect iron overload in the liver and extrahepatic siderosis.

A262 NEONATAL ACUTE LIVER FAILURE DUE TO PRESUMED GESTATIONAL ALLOIMMUNE LIVER DISEASE - A CASE REPORT

Abstract Background Neonatal acute liver failure (NALF) is a rare disease that is distinct from acute liver failure seen in older children and adults. Gestational alloimmune liver disease (GALD) is the most frequent cause, is initiated in utero by sensitization of the maternal immune system to a fetal hepatocyte antigen and subsequent production of maternal immunoglobulin G antibodies that cross the placenta. Maternal IgG binds to a fetal hepatocyte antigen and initiates an innate immune response involving the terminal complement cascade and membrane attach complex. The understanding of the alloimmune origin has led to the use of intravenous immunoglobulin (IVIG) treatment and exchange transfusion, significantly increasing survival. However, approximately 25% of patients may not respond and require salvage liver transplantation. In spite of an increased rate of comorbidities, concern for technical difficulties and limited graft availability, young infants eligible for transplant have been shown to have similar overall patient and graft survival rates compared to older children with other indications for liver transplant. Purpose The primary aim of our study is to report a case of NALF with successful liver transplant. Method We present the case of a preterm girl with NALF due to GALD refractory to medical management, requiring liver transplantation. Result(s) This is a 35-week preterm girl, with scant pre-natal care, birth weight of 1.825 kg and Apgar 9/9. She is the seventh child of non-consanguineous parents, with healthy siblings. On day-of-life (DOL) 1 she presented with acute kidney injury, progressive worsening metabolic acidosis and hyperammonemia and was found to be profoundly coagulopathic (INR 6), with normal liver enzymes and liver failure was diagnosed. Initial investigation ruled out congenital infections, sepsis, neonatal hemophagocytic lymphohistiocytosis and metabolic diseases. Magnetic resonance imaging of the body demonstrated findings in keeping with iron deposition in the thyroid, liver and pancreas, suggestive of GALD. Completed double volume exchange transfusion and IVIG on DOL 9 and repeat IVIG on DOL 13 and 15, with partial improvement in INR. Due to persistent ascites, conjugated hyperbilirubinemia and hyperammonemia she was transferred for urgent liver transplant assessment. Persistent liver dysfunction in the form of hyperammonemia, hypoglycemia and progressive coagulopathy led to transplant listing on DOL 30. ABO incompatible deceased donor liver transplant was completed on DOL 62 (4.075 kg, estimated dry weight 3.5 kg). The procedure was uncomplicated, liver enzymes normalized, coagulopathy and hypoglycemia resolved. She was transferred to the ward on post-operative day (POD) 6. and weaned off sedatives and transitioned to oral feeds within 2 weeks of transplant, with complex abdominal wound closure on POD 29. Conclusion(s) Successful liver transplantation is possible in neonates with acute liver failure due to GALD refractory to medical management and weighing 4kg or less. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared MICROBIOME &amp; MICROBIAL THERAPY

RNA-Sequencing Analysis Identifies Etiology Specific Transcriptional Signatures in Neonatal Acute Liver Failure.

To assess hepatic transcriptional signatures in infants with gestational alloimmune liver disease (GALD) compared with other etiologies of neonatal acute liver failure (ALF) and older pediatric patients with ALF. Neonates with ALF (international normalized ratio ≥2 within 30days of life) and deceased neonates without liver disease (<30days of age) with available liver tissue between 2010 and 2021 were identified at Ann & Robert H. Lurie Children's Hospital of Chicago. Clinical information, liver histology, and data from RNA-sequencing analysis was compared between neonates with GALD, non-GALD etiologies of neonatal ALF, and nondiseased neonatal liver. Quantification of trichrome staining showed an increase in fibrosis in patients with GALD vs those with non-GALD neonatal ALF (P=.012); however, quantification of α-cytokeratin 19-positive ductules did not differ between groups (P=.244). Gene set enrichment analysis of RNA-sequencing data identified the pathways of complement activation, fibrosis, and organogenesis to be upregulated in patients with GALD with ALF. In contrast, patients with non-GALD causes of neonatal ALF had increased gene expression for interferon-driven immune pathways. Individual genes upregulated in GALD included matrix metallopeptidase 7, hepatocyte growth factor, and chemokine ligand14. We have identified distinct pathways that are significantly upregulated in patients with GALD and potential disease-specific diagnostic biomarkers. Future studies will aim to validate these findings and help identify GALD-specific diagnostic biomarkers to improve diagnostic accuracy and reduce GALD-associated patient mortality.

Prevention of Gestational Alloimmune Liver Disease by Intravenous Immunoglobulin Administration in the Second Trimester: A Presentation of Two Cases

Prevention of Gestational Alloimmune Liver Disease by Intravenous Immunoglobulin Administration in the Second Trimester: A Presentation of Two Cases

Neonatal hemochromatosis with εγδβ-thalassemia: a case report and analysis of serum iron regulators

BackgroundNeonatal hemochromatosis causes acute liver failure during the neonatal period, mostly due to gestational alloimmune liver disease (GALD). Thalassemia causes hemolytic anemia and ineffective erythropoiesis due to mutations in the globin gene. Although neonatal hemochromatosis and thalassemia have completely different causes, the coexistence of these diseases can synergistically exacerbate iron overload. We report that a newborn with εγδβ-thalassemia developed neonatal hemochromatosis, which did not respond to iron chelators and rapidly worsened, requiring living-donor liver transplantation.Case presentationA 1-day-old Japanese boy with hemolytic anemia and targeted red blood cells was diagnosed with εγδβ-thalassemia by genetic testing, and required frequent red blood cell transfusions. At 2 months after birth, exacerbation of jaundice, grayish-white stool, and high serum ferritin levels were observed, and liver biopsy showed iron deposition in hepatocytes and Kupffer cells. Magnetic resonance imaging scans showed findings suggestive of iron deposits in the liver, spleen, pancreas, and bone marrow. The total amount of red blood cell transfusions administered did not meet the criteria for post-transfusion iron overload. Administration of an iron-chelating agent was initiated, but iron overload rapidly progressed to liver failure without improvement in jaundice and liver damage. He underwent living-donor liver transplantation from his mother, after which iron overload disappeared, and no recurrence of iron overload was observed. Immunohistochemical staining for C5b-9 in the liver was positive. Serum hepcidin levels were low and serum growth differentiation factor-15 levels were high prior to living-donor liver transplantation.ConclusionsWe reported that an infant with εγδβ-thalassemia developed NH due to GALD, and that coexistence of ineffective erythropoiesis in addition to erythrocyte transfusions may have exacerbated iron overload. Low serum hepcidin levels, in this case, might have been caused by decreased hepcidin production arising from fetal liver damage due to neonatal hemochromatosis and increased hepcidin-inhibiting hematopoietic mediators due to the ineffective hematopoiesis observed in thalassemia.

Neonatal Distant Transport for Liver Transplantation

A 36 weeks old baby boy was transferred interstate to the national paediatric liver transplant unit at the Children's Hospital, Westmead in Sydney for liver transplantation on Day 32 of life. Patient received liver transplantation at 41 weeks corrected age, which was three days after arrival to the transplant unit. This transfer involved road and aircraft ambulance utilization. We report this transport process in the setting of severe neonatal liver failure, complicated by persistent, uncorrectable coagulopathy, thrombocytopenia, ascites, hyperammonia and portal hypertension with particular reference to pre-transport preparations and the treatments undertaken during the difficult transport which spanned over eight hours. Keywords: Neonatal; Transport; Liver; Transplantation Abbreviations: FFP: fresh frozen plasma, PRBC: packed red blood cells, NICU: Neonatal Intensive Care Unit, PCH: Perth Children’s Hospital, NETS WA: Newborn Emergency Transfer Service of Western Australia, IVIG: intravenous immunoglobulin, GALD: gestational alloimmune liver disease, IgG: immunoglobulin G

Intravenous immunoglobulin induced pancytopenia while preventing development of gestational alloimmune liver disease: A case report

Gestational alloimmune liver disease is a rare complication associated with reactive maternal immunoglobulins resulting in neonatal liver pathology. The mainstay treatment for prevention in future pregnancies is intravenous immunoglobulins. Although relatively well tolerated, adverse reactions may occur. In this report, we highlight a case of intravenous immunoglobulin induced pancytopenia diagnosed by exclusion after thorough work-up. The patient was counseled on options and an informed decision was made to proceed with re-trial of intravenous immunoglobulin without systemic prednisone. This resulted in the delivery of a healthy neonate. We propose that future adverse reactions to intravenous immunoglobulin in pregnancy may warrant the trial of a new medication lot and use of systemic steroids only if subsequently indicated.

Pediatric Acute Liver Failure: A Clinicopathological Perspective

Pediatric acute liver failure (PALF) is a life-threatening disorder characterized by acute hepatocellular injury occurring in children without recognized underlying liver disease. The clinicopathologic evaluation of PALF requires a different approach from that in adults. The diagnostic considerations differ depending on the age, personal and family history, geographical region, and clinical presentation. Distinct entities such as gestational alloimmune liver disease, herpes simplex virus infection, and metabolic disorders should be considered in neonates with acute liver failure, while acetaminophen toxicity and autoimmune hepatitis are more frequently seen in older children and adolescents. An identified cause for PALF despite a negative complete evaluation (indeterminate) is lacking in 30 to 50% of cases. Although not routinely performed in the setting of PALF, liver biopsy may be helpful in assessing the etiology, potential mechanisms of injury, determining the appropriateness of liver transplantation, and prognostication of the patients. In this article, we review the clinicopathologic characteristics of PALF with an emphasis on general approach of pathologic evaluation and histopathologic characteristic of selected entities.

Could distal variants in ALG13 lead to atypical clinical presentation?

Congenital disorders of glycosylation (CDG) represent a wide range of some 150 inherited metabolic diseases, continually expanding in terms of newly identified genes and the heterogeneity of clinical and molecular presentations within each subtype. Heterozygous pathogenic variants in ALG13 are associated with early-onset epileptic encephalopathy, typically in females. The majority of subjects described so far harbour one of the two recurrent pathogenic variants, namely p.(Asn107Ser) and p.(Ala81Thr) in the C-terminal glycosyltransferase domain. We report a novel ALG13 variant (c.1709G > A, p.(Gly570Glu)) in an adult female with unremarkable past developmental and medical history, except for mild kinetic tremor. Our proband presented with acute onset of neurological and psychiatric features, along with liver dysfunction, during pregnancy, all of which gradually resolved after delivery. The proband's newborn baby died at 22 days of life from neonatal liver disease, due to gestational alloimmune liver disease (GALD). Functional assessment on fibroblasts derived from our case showed alterations in 2 of 3 cellular glycosylation markers (LAMP2, Factor IX), suggesting a functional effect of this novel ALG13 variant on glycosylation. This paper raises the possibility that variants outside the glycosyltransferase domain may have a hypomorphic effect leading to atypical clinical manifestations.

A Male Infant with Cholestatic Jaundice, Hemolytic Anemia, and Thrombocytopenia.

A Male Infant with Cholestatic Jaundice, Hemolytic Anemia, and Thrombocytopenia.

Hepatosplenomegaly and Periventricular Cyst in a Neonate with Direct Hyperbilirubinemia

Hepatosplenomegaly and Periventricular Cyst in a Neonate with Direct Hyperbilirubinemia

Gestational alloimmune liver disease treated with exchange transfusion and intravenous immunoglobulin: A case study

Gestational alloimmune liver disease (GALD) is a materno-fetal alloimmune disorder that targets the fetal liver and often causes neonatal liver failure. GALD most commonly presents as neonatal hemochromatosis (NH), which is a severe neonatal liver injury confirmed by extra-hepatic iron accumulation at various sites. With the discovery of the alloimmune mechanism of GALD, exchange transfusion and intravenous immunoglobulin (IVIG) administration are being used as novel treatments. Here, we present a rare case of an 11-day-old female infant who presented with marked hyperbilirubinemia. Laboratory findings showed significantly elevated direct and indirect bilirubin, high ferritin and alpha fetoprotein levels, high transferrin saturation, and severe coagulopathy. Abdominal magnetic resonance imaging revealed markedly reduced T2 signal intensity in the liver and pancreas compared to the spleen, suggesting iron deposition. The infant was diagnosed with NH and successfully treated with exchange transfusion and four doses of IVIG.

Neonatal hemochromatosis attributed to gestational alloimmune liver disease treated with intravenous immunoglobulin and exchange transfusion therapy: an evidence-based case report

Neonatal hemochromatosis (NH) is a rare fatal liver disease accompanied by hepatic and extrahepatic iron overload.1-3 Gestational alloimmune liver disease (GALD) is a materno-fetal alloimmune disorder and leading cause of NH.2,4,5 This condition allows an interplay between the maternal adaptive immune system and the fetus, resulting in an allograft to the mother. The mother becomes sensitized to an alloantigen expressed by the fetus and forms specific reactive antibodies. Immunoglobulin G (IgG) is transported through the placenta and attacks the fetal hepatocytes, resulting in severe loss of hepatocytes and fetal iron overload.3,6&#x0D; Liver transplantation has been the only definitive treatment for NH for many years, with a survival rate of ±35%. Conventional therapy containing antioxidants and chelation agents reportedly have very poor success, with survival rate of only 10-20%. A new treatment paradigm involving intravenous immunoglobulin (IVIG) and exchange transfusion (ET) therapy has shown significant success in survival rate in NH, decreasing the need for liver transplantation.3,7,8&#x0D; Here we present a case of NH caused by GALD and treated successfully with a combination of IVIG therapy and ET. We also aimed to evaluate the efficacy of IVIG and ET therapy for NH.

Efficacy of Intravenous Immunoglobulin/Exchange Transfusion Therapy on Gestational Alloimmune Liver Disease.

Background: Gestational alloimmune liver disease (GALD) is a rare but critical cause of neonatal liver failure. After discovering the maternal–fetal alloimmune mechanism, intravenous immunoglobulin (IVIG) with or without exchange transfusion (ET) has gradually replaced antioxidant cocktails as the first-line therapy. Whether such therapy changes the outcome of neonates with GALD is yet to be defined.Method: We reported a pair of twins with discordant presentations, mild and self-limited in the older, whereas liver failure in the younger, who was successfully rescued by ET and IVIG. To investigate the outcome after therapeutic alteration, 39 cases between 2005 and 2020 from literature research were collected.Results: Half of the collected cases (47.1%) were preterm. Common presentations were ascites, jaundice, respiratory distress, hepatomegaly, and edema. Leading laboratory abnormalities were coagulopathy, hypoalbuminemia, and elevated serum ferritin. Salivary gland biopsy and magnetic resonance imaging detected extrahepatic siderosis in 70% (14/20) and 56% (14/25), respectively. IVIG, ET, and liver transplantation were performed in 19 (48.7%), 15 (38.5%), and 8 (20.5%) patients, respectively. The overall survival (OS) rate and native liver survival (NLS) rate were 64.1% (25/39) and 43.6% (17/39), respectively. Although the compiled results did not support a significant benefit, the OS and NLS were higher in the IVIG with/without ET group compared with those treated with conventional therapy [OS (70 vs. 57.9%) and NLS (55 vs. 31.6%), respectively].Conclusion: A high index of suspicion for GALD is crucial when facing a neonate with liver failure. Despite no significant influence on the outcome over conventional therapy in such a rare and detrimental disease, IVIG with or without ET can be worth trying before resorting to liver transplantation, which is resource-demanding and technique-challenging in small infants.

MO675HEMOADSORPTION WITH CYTOSORB® CARTRIDGE IN PEDIATRIC INTENSIVE CARE UNIT – A SERIES OF FOUR CASES

Abstract Background and Aims Hemoadsorption with Cytosorb® cartridge is one of extracorporeal blood purification therapies increasingly used in adult intensive care units in conditions with elevated inflammatory mediators. Many positive experiences of hemodynamic improvement of patients treated with hemoadsorption have resulted in attempts of its application also in critically ill pediatric patients. Here we present a case series of four children treated with hemoadsorption in pediatric intensive care unit (PICU) of University Medical Centre Ljubljana from September 2018 to January 2019. Method All patients were mechanically ventilated and required vasopressor and inotropic support. Hemoadsorption was used as a rescue therapy after all standard treatments for their underlying condition had been insufficient. CytoSorb® cartridge was coupled with continuous veno-venous hemodialysis (CVVHD, Prismaflex system, Gambro) in pre-filter (ST60 set, Gambro) position. In children &amp;lt;10 kg body weight (2 infants), the extracorporeal circuit was prefilled with a 1:1 mixture of packed red blood cells and saline, with heparin added. Automated regional citrate anticoagulation was used, blood flow was 30-100 ml/min and dialysate flow 500 ml/h. Results The youngest child was 10 days old 1.9 kg premature female with acute liver failure due to gestational alloimmune liver disease. CVVHD was started for hyperammonemia and concomitant CytoSorb® for severe hyperbilirubinemia (335 umol/l). Procedure was discontinued after 6 hours due to uncontrollable sepsis and hemodynamic collapse. We managed to normalize ammonia values and reduce bilirubin concentration (116 umol/l). Further treatment was withdrawn as a result of irreversible multiorgan failure. One month old 2.5 kg female patient was treated in PICU due to necrotizing enterocolitis and refractory septic shock with multiorgan failure. Oliguric acute kidney injury (AKI) required CVVHD and later on Cytosorb ® was added as an attempt to limit severe hyperinflammatory condition. During 19 hours of treatment the need for vasopressor support was increasing and metabolic acidosis was deepening. The patient required a short resuscitation a couple of hours into the procedure due to bradycardia which resulted in catheter and CVVHD circuit thrombosis. Dialysis was discontinued as urgent surgery was necessary. The patient later died of uncontrolled septic shock. Three years old 17 kg male was admitted with meningococcal septic shock, requiring initiation of veno-arterial ECMO. Cytosorb® with CVVHD was started and attached to the ECMO circuit. A significant decline of interleukine-6 (IL-6) was achieved without any procedure-related side effect and treatment was discontinued after 68 hours as patient's clinical status notably improved. The patient survived. Five years old 20 kg female patient, actively treated for acute lymphoblastic leukemia, was admitted with E. coli sepsis. Septic shock was unresponsive to conventional treatment therefore she was started on Cytosorb® with CVVHD as oliguric AKI also developed. Two consecutive procedures were preformed, the first for 31 and the second for 37 hours. Level of IL-6 decreased (from &amp;gt; 5000 ng/L to 1000 ng/L) and lactate level normalized. We achieved reduction in vasopressors and oxygen need during both procedures and patient's overall status greatly improved. Conclusion Although significantly increasing the volume of extracorporeal circuit, the use of Cytosorb® cartridge within CVVHD circuit is technically feasible even in critically ill children with low body weight, if principles of pediatric renal replacement therapy are considered. More efficacy and safety data on Cytosorb® utilization are necessary before inclusion in routine clinical practice. Treatment outcome is highly dependent on primary disease and severity of patient condition.