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

Abstract

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.

Acute liver failure related to inherited metabolic diseases in young children

“…Pediatric ALF etiology remains indeterminate in 18---47%, 1 depending upon the exhaustiveness of work-up screening, and it can even be higher in younger children, approaching 54% in children under 3 years, as reported by Squires et al 6 Early recognition of IMDs is crucial, because some require immediate initiation of specific therapy or diets that can be life-saving, mainly in the case of galactosemia, hereditary fructose intolerance and hereditary tyrosinemia type 1, 1 which can present during neonatal period with jaundice, hypoglycemia and sometimes with ALF. 8 In this case series, the lower number of patients with galactosemia and hereditary tyrosinemia type 1 presenting with ALF, compared to King's College experience, 9 may be attributed to the expanded Portuguese neonatal screening, available since 2005, which allows pre-symptomatic diagnosis of these diseases.…”

Neonatal acute liver failure: a diagnosis challenge

“…In these cases, the transaminase level is very high; postmortem histopathological liver findings showed generalized necrosis, sometimes with parenchymal collapse. 1,3 The most common virus is herpes simplex virus (HSV), which causes a broad range of clinical manifestations, from mucocutaneous involvement (skin, eyes, and mucous membranes) to neurological involvement (central nervous system), and even to disseminated disease. NALF may occur in the context of a disseminated or an isolated liver infection.…”

“…Metabolic disorders are rarely the cause of NALF. [1][2][3] Galactosemia, type 1 tyrosinemia, and hereditary fructose intolerance -all inherited autosomal recessive disorders-may occur in the neonatal period together with jaundice or hypoglycemia, and may occasionally progress to NALF. Out of these three conditions, galactosemia may be more common in the first month of life, once milk feeding is introduced.…”

“…Although these conditions may exceptionally be the cause of NALF, test costs are minimal, considering that they are treatable diseases. 1,2,[9][10][11][12] Respiratory chain (RC) defects account for a group of mitochondrial diseases. These organelles are in charge of generating energy in the form of adenosine triphosphate (ATP), an element that is essential for effective cell functioning.…”

“…Supportive treatment may also include sodium bicarbonate infusion during acute metabolic acidosis events, transfusions in the case of anemia and thrombocytopenia, and exogenous enzymes for patients with pancreatic insufficiency. 1,2,[12][13][14] A mutation in the TRMU gene (a protein involved in mitochondrial transfer RNA [tRNA] modifications) has been associated with NALF, which is sometimes transient. Patients who survive the initial episode may recover and grow normally.…”