To determine short-term outcome for children with acute liver failure (ALF) as it relates to cause, clinical status, and patient demographics and to determine prognostic factors.
A prospective, multicenter case study collecting demographic, clinical, laboratory, and short-term outcome data on children from birth to 18 years with ALF. Patients without encephalopathy were included if the prothrombin time and international normalized ratio remained > or = 20 seconds and/or >2, respectively, despite vitamin K. Primary outcome measures 3 weeks after study entry were death, death after transplantation, alive with native liver, and alive with transplanted organ.
The cause of ALF in 348 children included acute acetaminophen toxicity (14%), metabolic disease (10%), autoimmune liver disease (6%), non-acetaminophen drug-related hepatotoxicity (5%), infections (6%), other diagnosed conditions (10%); 49% were indeterminate. Outcome varied between patient sub-groups; 20% with non-acetaminophen ALF died or underwent liver transplantation and never had clinical encephalopathy.
Causes of ALF in children differ from in adults. Clinical encephalopathy may not be present in children. The high percentage of indeterminate cases provides an opportunity for investigation.
Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver disease in the world, but little is known about its potential association with pregnancy outcomes. We aimed to investigate pregnancy outcomes in NAFLD.
The Swedish Medical Birth Register (MBR) was used to identify births between 1992 and 2011 (N = 1 960 416). By linkage with the National Patient Register, we identified women with a diagnosis of NAFLD. The MBR was then used to identify outcomes: gestational diabetes, pre-eclampsia, Caesarean section, Apgar score
We studied age at diagnosis and disease progression of cystic fibrosis (CF) patients with a new study design, using data of 119 patients extracted from Stockholm CF Centre registry. Risk factors for overall morbidity and for lung, liver and nutritional morbidity were investigated separately using time to event methodology (Kaplan-Meier curves, proportional hazards regression). The patients were followed from: (i) healthy at diagnosis to morbidity, (ii) diagnosis with symptoms of morbidity to being free of morbidity, and (iii) free of morbidity to relapse of morbidity. Median age at diagnosis was 5.0 months. Of the patients with overall morbidity at diagnosis 50% became free of morbidity after 4.8 years; however, the patients above the age of 24 months at diagnosis had a reduced chance of becoming free of morbidity (crude hazard ratio 0.14 [95 % confidence interval 0.04, 0.45]) compared with those with diagnosis between the ages of 2 and 12 months (P
BACKGROUND: A prospective nationwide screening study initiated more than 20 years ago in Sweden has shown that clinically significant liver disease develops in only 10% to 15% of alpha1-antitrypsin (AT)-deficient children. This study provides information about 85% to 90% of those children, many of whom had elevated serum transaminases in infancy but have no evidence of liver injury by age 18 years. However, there is relatively limited information about the course of alpha1-AT-deficient children who have cirrhosis or portal hypertension. Based on several anecdotal experiences, we have been impressed by the relatively slow progression and stable course of the liver disease in some of these children. METHODS: We reviewed the course of patients with homozygous PIZZ alpha1-antitrypsin deficiency seen at this institution since establishing a patient database 16 years ago. RESULTS: Of 44 patients with alpha1-AT deficiency, 17 had cirrhosis, portal hypertension, or both. Nine of the 17 patients with cirrhosis or portal hypertension had a prolonged, relatively uneventful course for at least 4 years after the diagnosis of cirrhosis or portal hypertension. Two of these patients eventually underwent liver transplantation, but seven are leading relatively healthy lives for up to 23 years while carrying a diagnosis of severe alpha1-AT deficiency-associated liver disease. Patients with the prolonged stable course could be distinguished from those with a rapidly progressive course on the basis of overall life functioning but not on the basis of any other more conventional clinical or biochemical criteria. CONCLUSIONS: These data provide further evidence for the variable severity of liver disease associated with alpha1-AT deficiency and indicate that some patients have chronic, slowly progressing or nonprogressing cirrhosis.
A prenatal diagnosis of the fetus for a mother of two previously deceased infants who died from the recently described autosomal recessive disease (OMIM 603358). The infants presented with intrauterine growth retardation, aminoaciduria, cholestasis, iron overload, severe lactic acidosis, and early death (GRACILE syndrome).
DNA was extracted from the fibroblasts and tissue samples of the deceased infants, parental leukocytes, and from a chorion villus biopsy in the next pregnancy. Haplotypes were determined using the relevant markers flanking the disease-associated region of chromosome 2.
Both deceased infants were homozygous for the four critical markers. The fetal haploptypes were identical to those of the siblings and the pregnancy was terminated. The iron content of the fetal liver was increased (5000 microg/g) compared with the controls, with a marked iron accumulation in the Kupffer cells.
Antenatal diagnosis can be performed based on linkage analysis in families with at least one affected child because the disease locus has been assigned to a restricted chromosomal region. Typical histological abnormalities may be present in early fetal life.
A new neonatal syndrome characterized by intrauterine growth retardation, lactic acidosis, aminoaciduria, liver hemosiderosis, and early death was recently described. The pathogenesis of this disease is unknown. The mode of inheritance is autosomal recessive, and so far only 17 cases have been reported in 12 Finnish families. Here we report the assignment of the locus for this new disease to a restricted region on chromosome 2q33-37. We mapped the disease locus in a family material insufficient for traditional linkage analysis by using linkage disequilibrium, a possibility available in genetic isolates such as Finland. The primary screening of the genome was performed with samples from nine affected individuals in five families. In the next step, conventional linkage analysis was performed in eight families, with a total of 12 affected infants, and finally the locus assignment was proved by demonstrating linkage disequilibrium to the regional markers in 20 disease chromosomes. Linkage analysis restricted the disease locus to a 3-cM region between markers D2S164 and D2S2359, and linkage disequilibrium with the ancestral haplotype restricted the disease locus further to the immediate vicinity of marker D2S2250.
Cites: Am J Hum Genet. 1995 May;56(5):1088-957726163
Cites: Am J Hum Genet. 1998 Aug;63(2):506-169683599
A deficiency of the major serum alpha1-globulin, the alpha1-antitrypsin, was first described in five patients by Laurell and Eriksson in Sweden in 1963. It soon became obvious that severe alpha1-antitrypsin deficiency was familial, and highly associated with chronic lung disease, having its onset in the third or fourth decade of life. Since the early descriptions of this common deficiency state, it has become clearly associated with familial emphysema in some families, familial infantile cirrhosis in others, and occasionally with a combination of childhood lung and liver disease in siblings. For the pediatrician, severe alpha1-antitrypsin deficiency now enters into the differential diagnosis of both chronic pulmonary disease in childhood and obstructive jaundice in the newborn period; In addition, low levels of alpha1-antitrypsin in serum are characteristic of respiratory distress syndrome, and elevations of this protein may be found in a variety of clinical situations. The, alpha1-antitrypsin probably functions as a major control protein against the tissue-damaging effects of both endogenous and exogenous enzymes. This review will cover several basic and clinical features of this protein with respect to its importance in pediatrics.