Cause Of Neonatal Liver Failure Research Articles

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.

Magnetic Resonance Imaging Findings in Neonatal Hemochromatosis.

There are limited data on utility of magnetic resonance imaging (MRI) in the assessment of suspected neonatal hemochromatosis (NH). The aim of the study was to present our experience with utilization of multi-echo sequence MRI technique in the evaluation of NH and to compare MRI findings in infants with and without NH. MRI performed for suspected NH were retrospectively reviewed to note the presence and severity of iron deposition (ID) in liver, spleen, pancreas, and kidneys on multi-echo sequences. Findings were compared in infants with and without NH. Of 20 infants (9 boys and 11 girls; median age of 12.5 days) included in the study, 7 of 20 had NH and 13 of 20 were assigned to the non-NH group. Higher degree of pancreatic ID was seen in the NH group (P = 0.001) with 4 of 7 evaluable pancreas showing moderate-to-severe degree and 1 of 7 showing mild degree of ID whereas none of the 13 infants in non-NH group showed moderate or severe degree of pancreatic ID. Even though the severity of hepatic ID was higher in NH group (P = 0.033), variable severity of hepatic ID was seen in both groups with most infants in both groups showing moderate-to-severe degree of ID. The severity of splenic ID was not particularly associated with any group (P = 0.774) but there was no moderate or severe degree of ID in NH. Renal ID was seen in two infants in non-NH group. A moderate-to-severe degree of pancreatic ID seen on MRI tends to be associated with NH and should be sought to establish a timely diagnosis of NH. Presence and severity of hepatic ID cannot be used for differentiation of NH from other causes of neonatal liver failure.

Neonatal liver failure: A refractory case to medical treatment

Neonatal liver failure (NLF) is rare and carries a high mortality. Common aetiologies include neonatal haemochromatosis (NH), haematological malignancies, viral infections and liver-based metabolic defects. Early diagnosis and referral to a paediatric liver centre is recommended as liver transplantation is the only definitive treatment when supportive or a disease-specific treatment fails. A baby girl was born by Emergency LSCS for pathological cardiotocography at 33+2 weeks of gestation. Her mother had been previously well and had normal pregnancy. She was birth in poor condition requiring cardiopulmonary resuscitation. She was transferred to a level 2 neonatal unit for ventilator management. At birth she had coagulopathy which remained refractory to medical treatment. She required multiple ionotropes, multiple blood products and high dextrose load. She was transferred to a tertiary neonatal unit for the management of acute renal failure. With persistent evidence of only marginally raised liver enzymes and significantly reduced synthetic and excretory function of liver it was unlikely to be explained by solely bacterial or viral illness. Extensive infection screen were negative. Metabolic screening tests were done. She was referred to liver unit. Lip biopsy confirmed the diagnosis of NH. She had a liver transplant on day 36 of life. Histology showed nodular cirrhosis secondary to neonatal haemochromatosis. At age 4 months, she is continuing to thrive well with normal liver function tests. NH is the single most common cause of NLF (40%) and usually presents with severe neonatal liver disease associated with hepatic and extrahepatic iron deposition but sparing the reticulo-endothelial system. NH is hypothesised to be an alloimmune process where maternal antibodies are directed towards fetal liver antigen. Rate of recurrence in subsequent pregnancy is up to 80% and could be effectively prevented by antenatal intravenous immunoglobulin. Early and aggressive medical treatment is essential for improving the outcome. Treatment conundrum of NH continues with some case series showing a success rate of 10 to 20% following a ‘cocktail’ of antioxidants and chelating agents which have not been evaluated systematically and liver transplantation remains the only definitive treatment.

Neonatal liver failure: aetiologies and management—state of the art

Acute liver failure in neonates is rare, but carries a high mortality. Neonatal liver failure can be defined as "failure of the synthetic function of liver within 4 weeks of birth". Encephalopathy is not essential for the diagnosis. Acute liver failure in neonates differs from children with regard to aetiology and outcome. Common causes of neonatal liver failure are neonatal hemochromatosis, haematological malignancies, viral infections and liver-based metabolic defects. Early diagnosis and referral to a paediatric liver centre is recommended as liver transplantation is the only definitive treatment when supportive or a disease-specific treatment fails.

Neonatal liver failure: a genetic and metabolic perspective

Liver failure in newborns can present formidable diagnostic challenges. The presentation of neonatal liver failure is variable and the initial assessment is crucial in the determination of potentially treatable causes. We present a case of neonatal hemochromatosis, review genetic and metabolic causes of neonatal liver failure, and outline an updated differential diagnosis of neonatal liver failure. In addition, we propose a comprehensive initial work-up of neonatal liver failure, and review current treatments for neonatal hemochromatosis.

Labial salivary gland involvement in neonatal hemochromatosis: a report of 2 cases and review of literature

Neonatal hemochromatosis (NH) is a severe disease of fetal or perinatal onset, in which iron deposition occurs within hepatic and extrahepatic sites without involving the reticuloendothelial system. Labial minor salivary gland biopsy has been suggested as a diagnostic adjunct in patients suspected of having NH, as hemosiderin accumulates in acinar epithelial cells. Prior to this salivary gland pathology, a diagnosis of NH was often delayed, rendered only after the usual causes of neonatal liver failure had been excluded. Recent studies have shown that early diagnosis and treatment can improve survival. Few cases of salivary gland hemosiderosis in NH have been reported in the literature. A positive finding of salivary gland siderosis on biopsy will expedite care. We report 2 cases of NH, of which a labial salivary gland biopsy supported the diagnosis. The clinical and histological features are presented. The NH literature pertaining to labial salivary gland pathology is reviewed.

Index of Suspicion in the Nursery

A 36-week estimated gestational age male infant is born via spontaneous vaginal delivery to a 26-year-old G2P2 woman following a pregnancy complicated by late oligohydramnios. He cries spontaneously and receives routine resuscitation (Apgar scores of 8 and 9 at 1 and 5 minutes, respectively). The infant is symmetrically small for gestational age but has otherwise normal findings on physical examination. He is transferred to the newborn nursery for normal transition. Shortly after birth, he develops profound hypoglycemia with a glucose value of 5.0 mg/dL (0.28 mmol/L) and is transferred to the neonatal intensive care unit for further management. The hypoglycemia resolves with administration of intravenous dextrose-containing fluids, but on the second postnatal day, he develops direct hyperbilirubinemia. Liver transaminase values are normal despite the elevation of direct bilirubin. Over the next several days, the infant continues to have direct hyperbilirubinemia (peak bilirubin, 15.8 mg/dL [270.2 mcmol/L]), hypoalbuminemia (albumin, 1.5 g/dL [15 g/L]), and increasing blood urea nitrogen/creatinine values as well as the onset of oliguria, hypotension, and increasing diffuse edema. Hepatic and renal ultrasonography is interpreted as normal. Echocardiography shows a small patent ductus arteriosus but appears otherwise normal. Dopamine administration is initiated, and the infant responds well. A TORCH evaluation is initiated to look for the presence of congenital infection and later is found to be negative. The patient begins to have spontaneous bleeding from his umbilical artery catheter site and is found to have a coagulopathy, with a prothrombin time of 114.5 seconds and a partial thromboplastin time of more than 150 seconds in conjunction with thrombocytopenia. Due to his severe coagulopathy, hypotension, and oliguric renal failure, the patient is transferred to a tertiary care facility. On his second hospital day, he is intubated because of a spontaneous pulmonary hemorrhage that resolves. He continues to have persistent coagulopathy, …

Clinical, biochemical and morphological features of hepatocerebral syndrome with mitochondrial DNA depletion due to deoxyguanosine kinase deficiency

The aim of this study was to delineate the specific clinical, biological and liver morphological alterations of the hepatocerebral syndrome due to alterations in the deoxyguanosine kinase gene, a rare and severe form of mitochondrial DNA depletion syndrome. We report seven cases from three unrelated families with the same mutation in the deoxyguanosine kinase gene. All the patients presented in the first weeks of life with hepatomegaly and progressive liver failure that led to death few months later. Major psychomotor delay and multidirectional nystagmus were reported shortly after onset of the disease. Severe hyperlactacidaemia was constant. Histological examination of the liver disclosed a multifocal injury of hepatocytes with irregular foamy steatosis, cholestasis, and fibrosis, associated with different degrees of hepatosiderosis and glycogen depletion. Liver respiratory chain activities were abnormal in all analysed patients and the amount of liver mitochondrial DNA was severely decreased. An identical homozygous 4bp GATT duplication was identified in the deoxyguanosine kinase gene of all the cases. These patients, together with patients reported in the literature, permit to delineate the specific features of the hepatocerebral form of mitochondrial DNA depletion syndrome and to differentiate them from other causes of neonatal liver failure.