RESUMO
We studied, retrospectively, 92 children who were first seen with neonatal cholestasis and who were followed up until liver test results normalized. Among the 92 children, 81 displayed factors responsible for chronic and/or acute perinatal distress. Onset of jaundice was recorded at a mean age of 7 days, and mean duration was 3.5 months. Stools, initially discolored in 39 children, were normally colored at a mean age of 1.7 months. Hepatomegaly present in 90 children resolved at a mean age of 13 months. Liver test results were normal at the age of 1 year in 83 children and normalized at a mean age of 10 months. Liver histologic examination, performed in 70 children, showed moderate portal and lobular fibrosis, multinucleated giant hepatocytes, and hematopoietic foci; findings in follow-up liver biopsy specimens from 15 children were normal or improved. Spontaneously resolving forms of neonatal cholestasis may result from the association of several factors, including immaturity of bile secretion and perinatal disease leading to hepatic hypoxia or ischemia.
Assuntos
Colestase/diagnóstico , Alanina Transaminase/sangue , Biópsia , Colangiografia , Colestase/tratamento farmacológico , Colestase/genética , Feminino , Seguimentos , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Fígado/patologia , Masculino , Tempo de Protrombina , Estudos Retrospectivos , Vitamina K/uso terapêuticoRESUMO
Inborn errors of oxidative phosphorylation have been recognized as possible causes of hepatic failure in the neonate, and respiratory enzyme deficiencies have been described in the liver of affected individuals. On the basis of a series of 22 cases, we describe respiratory enzyme deficiency as a cause of early-onset fatal hepatic failure with frequent neurologic involvement. In addition, we have identified a delayed-onset form of hepatic failure with a milder clinical course and inconstant neurologic involvement. Thus we suggest that genetic defects of oxidative phosphorylation be considered as a cause of liver dysfunction in infancy, regardless of the severity of the disease.
Assuntos
Falência Hepática/genética , Erros Inatos do Metabolismo/genética , Complexos Multienzimáticos/deficiência , Fosforilação Oxidativa , Alanina Transaminase/metabolismo , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Falência Hepática/enzimologia , Falência Hepática/mortalidade , Erros Inatos do Metabolismo/enzimologia , Complexos Multienzimáticos/metabolismoRESUMO
There have been a few reports of infants with severe neonatal cholestasis related to a defect in primary bile acid synthesis. To assess the importance of such deficiency among children with progressive intrahepatic cholestasis (Byler disease), screening for inborn errors in bile acid synthesis was performed by fast atom bombardment ionization-mass spectrometry of urine samples from 30 affected children. Bile acid analysis revealed a specific fast atom bombardment ionization-mass spectrometry profile for 3 beta-hydroxy-C27 steroid dehydrogenase/isomerase deficiency in five children who had jaundice, hepatosplenomegaly, and fatty stools beginning at ages ranging from 4 to 46 months. None of them had pruritus. Liver function tests showed persistently normal serum gamma-glutamyltransferase activity, low serum cholesterol and vitamin E levels, normal serum bile acid concentrations despite raised serum bilirubin levels, and decreased prothrombin time and clotting factor V. In four of the cases a similar disease was observed in siblings. Liver function returned to normal after oral ursodeoxycholic acid therapy. We conclude that 3 beta-hydroxy-C27-steroid dehydrogenase/isomerase deficiency should be considered when idiopathic cholestatic liver disease with clinical features akin to Byler disease is characterized by the association of normal serum gamma-glutamyltransferase activity, normal serum bile acid concentration, absence of pruritus, and a return to normal liver function during ursodeoxycholic acid therapy. Early identification of these children is essential because they benefit from bile acid therapy and might thus avoid the need for liver transplantation.
Assuntos
Colestase Intra-Hepática/etiologia , Complexos Multienzimáticos/deficiência , Progesterona Redutase/deficiência , Esteroide Isomerases/deficiência , Alanina Transaminase/sangue , Ácidos e Sais Biliares/sangue , Ácidos e Sais Biliares/urina , Bilirrubina/sangue , Criança , Pré-Escolar , Colestase Intra-Hepática/sangue , Colestase Intra-Hepática/tratamento farmacológico , Colestase Intra-Hepática/patologia , Colesterol/sangue , Seguimentos , Hepatite/patologia , Humanos , Lactente , Fígado/fisiopatologia , Cirrose Hepática/patologia , Estudos Retrospectivos , Ácido Ursodesoxicólico/uso terapêutico , Vitamina E/sangue , gama-Glutamiltransferase/sangueRESUMO
We report on 56 children with sclerosing cholangitis (SC) seen between 1972 and 1992. The first symptoms occurred at a mean age of 3.7 years; 15 infants had neonatal cholestatic jaundice. At diagnosis, cholestatic jaundice was present in 25 children, hepatomegaly in 54, splenomegaly in 41, and ascites in 12. Serum alkaline phosphatase activity was increased in 49 patients and gamma-glutamyltransferase activity in all patients tested. Most often the histopathologic findings were extensive portal fibrosis and neoductular proliferation. Cholangiography showed abnormal intrahepatic bile ducts in all children and abnormal extrahepatic bile ducts in 35 (63%). The children were separated into three groups: (1) those with SC of neonatal onset (27%); (2) those with SC of postneonatal onset associated with another disease (55%)--histiocytosis X in 14 children, immunodeficiency syndromes in 8, chronic inflammatory bowel disease or autoimmune hepatitis in 8, and congenital psoriasis in 1; and (3) those with SC of postneonatal onset without an associated disease (18%). Biliary cirrhosis was present in all but three children after 6 months to 19.3 years of follow-up. Eleven children died of portal hypertension or liver failure, and six died of a complication related to the associated disease. Fifteen children had liver transplantation; 11 of these are alive 6 months to 6 1/2 years later without recurrence of SC. The overall estimated median survival time of children with SC was 10 years from clinical onset. These results indicate that SC should be suspected in all children with a chronic cholestatic disease and increased serum gamma-glutamyl transferase activity, especially when diseases known to be associated with SC are present. The prognosis is poor, but liver transplantation should be considered except in those with severe immunodeficiency syndromes.
Assuntos
Colangite Esclerosante , Adolescente , Criança , Pré-Escolar , Colangiografia , Colangite Esclerosante/complicações , Colangite Esclerosante/diagnóstico , Colangite Esclerosante/mortalidade , Colangite Esclerosante/terapia , Feminino , Seguimentos , Hepatite Crônica/complicações , Hepatite Crônica/imunologia , Histiocitose de Células de Langerhans/complicações , Humanos , Síndromes de Imunodeficiência/complicações , Lactente , Recém-Nascido , Doenças Inflamatórias Intestinais/complicações , Icterícia Neonatal/etiologia , Masculino , Prognóstico , Análise de SobrevidaRESUMO
Three children with Kawasaki disease had liver biopsies because of evidence of hepatic disease. Cholangitis or bile duct injury and proliferation were found. Similar damage to the hepatic ductular system may explain the hydrops of the gallbladder sometimes seen in this disease.
Assuntos
Ductos Biliares Intra-Hepáticos/patologia , Colangite/etiologia , Síndrome de Linfonodos Mucocutâneos/complicações , Biópsia , Criança , Pré-Escolar , Colangite/patologia , Humanos , Testes de Função Hepática , Síndrome de Linfonodos Mucocutâneos/patologiaRESUMO
To determine the incidence of liver cirrhosis in children with chronic hepatitis, we investigated 92 children (64 were girls; mean age was 8 years 2 months) with chronic hepatitis for the presence of cirrhosis by the combined use of laparoscopy and needle liver biopsy, between 1975 and 1985. Forty-six children had hepatitis B virus-related chronic hepatitis; cirrhosis was present in 13 (32%). Cirrhosis was diagnosed by laparoscopy in 14 children and by needle liver biopsy in eight. In six patients, cirrhosis was diagnosed within the first 12 months after the clinical onset of liver disease. Forty-six children had autoimmune hepatitis; cirrhosis was present in 41 (89%). Cirrhosis was diagnosed by laparoscopy in all 41 children and by needle liver biopsy in 23 children. Cirrhosis was already present in all 10 children studied 2 to 5 months after the first sign of liver disease. Our results indicate that the incidence of cirrhosis is high in children with chronic hepatitis, especially of the autoimmune type, and that cirrhosis may occur early, irrespective of cause. A combination of laparoscopy and biopsy is more reliable than biopsy alone for the diagnosis of cirrhosis in children with chronic hepatitis.
Assuntos
Hepatite/complicações , Cirrose Hepática/complicações , Adolescente , Biópsia por Agulha , Criança , Doença Crônica , Feminino , Hepatite/epidemiologia , Humanos , Cirrose Hepática/epidemiologia , Cirrose Hepática/patologia , Testes de Função Hepática , Masculino , Estudos RetrospectivosRESUMO
An autosomal dominant transmission of arteriohepatic dysplasia, or Alagille syndrome, with reduced penetrance and variable expressivity has been suggested from familial pedigrees, but the nature of the genetic defect and its chromosomal localization are not firmly established. We report the case of an 8-year-old boy with arteriohepatic dysplasia, in whom high-resolution chromosome study showed a partial deletion of the short arm of chromosome 20, which encompasses subbands p11.23 to p12.3. In situ hybridization and Southern blotting localized four restriction fragment length polymorphism probes within the deletion and another one distal to the deletion. Because one patient has already been reported to have arteriohepatic dysplasia and deletion of the short arm of chromosome 20, and six additional patients with such a deletion had major features of Alagille syndrome, this syndrome should now be assigned to chromosome 20p.
Assuntos
Ductos Biliares/anormalidades , Colestase Intra-Hepática/genética , Deleção Cromossômica , Cromossomos Humanos Par 20 , Artéria Pulmonar/anormalidades , Coluna Vertebral/anormalidades , Southern Blotting , Criança , Doença Crônica , Humanos , Cariotipagem , Masculino , Hibridização de Ácido Nucleico , Polimorfismo de Fragmento de Restrição , SíndromeRESUMO
Clinical, radiologic, and histologic features in 22 children with Budd-Chiari syndrome are reported. Three children had acute refractory ascites; all the others had hepatomegaly, which was detected either fortuitously or because of abdominal pain or distention. Results of liver function tests were normal or only moderately abnormal. In most cases a combination of ultrasonography and needle liver biopsy pointed to the diagnosis of Budd-Chiari syndrome, which was confirmed by angiography. Eighteen children underwent surgery involving various techniques, depending on the degree of patency of the inferior vena cava. Five children died postoperatively. Histologic studies of the liver, carried out in 12 of the surviving children, showed disappearance or regression of centrilobular hemorrhagic infiltration. Half of the surviving surgical patients are now free of complications after a follow-up of 7 months to 7 years; the others have either secondary thrombosis of the inferior vena cava or stenosis of the shunt or have experienced late pulmonary complications. Our results suggest that (1) Budd-Chiari syndrome must be considered a possible diagnosis in children with firm hepatomegaly and normal or near normal liver function, (2) surgery provides good results in many instances, and (3) the possibility of late complications requires careful follow-up.
Assuntos
Síndrome de Budd-Chiari , Síndrome de Budd-Chiari/diagnóstico por imagem , Síndrome de Budd-Chiari/patologia , Síndrome de Budd-Chiari/fisiopatologia , Síndrome de Budd-Chiari/cirurgia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Hipertensão Portal/fisiopatologia , Masculino , Radiografia , Ultrassonografia , Veia Cava Inferior/diagnóstico por imagemRESUMO
We retrospectively studied the incidence of bacterial cholangitis in 129 infants operated on because of biliary atresia over 5 years. Forty-six of the 101 children who underwent hepatic portoenterostomy had a total of 105 episodes of cholangitis (range one to eight episodes per child). Most episodes occurred within 3 months of the operation. Factors associated with cholangitis included good or partial restoration of bile flow, abnormal intrahepatic bile ducts or cavities at the porta hepatis, and routine postoperative use of antibiotics. External jejunostomy was not effective in preventing cholangitis. In addition to fever and decreased bile flow, increased erythrocyte sedimentation rate and signs of shock were frequently observed. The responsible organisms, most often gram-negative bacteria, were identified in 79 (75%) episodes by blood or liver cultures. Most were susceptible to trimethoprim-sulfamethoxazole and third-generation cephalosporins during the first episode, but only to cephalosporins during later episodes. The incidence of signs of portal hypertension in children with normal serum bilirubin values at age 5 years was not higher in those who had previously experienced one or more episodes of cholangitis.
Assuntos
Atresia Biliar/cirurgia , Colangite/etiologia , Portoenterostomia Hepática/efeitos adversos , Infecção da Ferida Cirúrgica/complicações , Humanos , Lactente , PrognósticoRESUMO
Sclerosing cholangitis is characterized by irregular narrowing of extrahepatic or intrahepatic bile ducts, and in adults is defined mainly by radiologic findings. We describe eight children with cholestasis from the first week of life, followed by early cirrhosis and portal hypertension. Histologic examination of the liver showed absence of interlobular bile ducts in the early cholestatic phase in two patients and biliary cirrhosis later in all patients. Radiologic examination by percutaneous cholecystography under ultrasound guidance, carried out at age 8 months to 9 years, disclosed abnormal intrahepatic bile ducts with rarefaction of segmental branches, stenosis, and focal dilation. The extrahepatic ducts were involved in six patients. No intestinal disease has been found in these patients.
Assuntos
Ductos Biliares/patologia , Colangite/diagnóstico , Criança , Pré-Escolar , Colangiografia , Colangite/metabolismo , Colangite/patologia , Feminino , Humanos , Lactente , Recém-Nascido , Fígado/patologia , Cirrose Hepática/patologia , Masculino , EscleroseRESUMO
We have observed two types of paucity of interlobular bile ducts (PILBD) in children with chronic cholestasis: the syndromic type, which is more frequent (80 cases), and the nonsyndromic type (31 cases). Study of patients with syndromic PILBD has enabled us to recognize five major features: peculiar facies (95%), chronic cholestasis (91%), posterior embryotoxon (88%), butterfly-like vertebral arch defects (87%), and peripheral pulmonary artery hypoplasia or stenosis, either isolated or associated with complex cardiovascular abnormalities (85%). By observing these major features, it is possible to differentiate the "complete" syndrome, in which all five features are present (26 cases), from the "partial" syndrome, in which only four (42 cases) or three (12 cases) major features are present. Other less frequent features were observed in patients with complete or partial syndrome: growth retardation (50%), mental retardation (16%), renal disturbances, other vascular malformations, bone abnormalities, high-pitched voice, and delayed puberty. Death occurred in 21 (26%) patients with syndromic PILBD. Therapy consisted of supplementation of medium-chain triglycerides and fat-soluble vitamins and administration of cholestyramine or phenobarbital. An autosomal dominant mode of transmission, with variable penetrance, seems likely.
Assuntos
Ductos Biliares Intra-Hepáticos/anormalidades , Anormalidades Cardiovasculares , Criança , Pré-Escolar , Colestase/fisiopatologia , Face/anormalidades , Humanos , Lactente , Coluna Vertebral/anormalidades , SíndromeRESUMO
In the past 10 years we have examined 20 children with inflammatory liver disease associated with high serum titers of anti-liver-kidney microsome antibody (anti-LKM). The first hepatic symptoms were progressive fatigue and jaundice, the fortuitous finding of hepatomegaly or splenomegaly with raised transaminase activity, or an acute hepatitis-like illness. At the time of diagnosis, hepatomegaly was present in 18 children, splenomegaly in 16, jaundice in nine, and ascites in two. Serum alanine transferase activities were elevated in all but two, who had already received steroids. Serum total gammaglobulin values were greater than 2.0 gm/dl in 16 children, prothrombin activity less than or equal to 60% in six, and serum titer of anti-LKM between 1:100 and 1:100,000. All children but one had cirrhosis, and histologic signs of aggressivity were present in 14. In 11 children one or more extrahepatic diseases were present, including type 1 diabetes, vitiligo, glomerulonephritis, autoimmune hemolytic anemia, hypoglycemia with hyperinsulinism, autoimmune thyroiditis, chronic mucocutaneous candidiasis with hypoparathyroidism, and multiple cutaneous and visceral telangiectasias. Treatment with prednisone and azathioprine improved the liver condition in 16 of the 18 patients given treatment. In eight of them discontinuation of treatment resulted in rapid relapse; 14 are still receiving treatment and have stable hepatic function with follow-up from 8 months to 6 1/2 years. Only two are free of treatment. Four children died, two in spite of immunosuppressive therapy, one during a relapse, and one of extrahepatic disease. These results indicate that this autoimmune inflammatory liver disease may have onset early in life, with several clinical patterns; is frequently associated with certain types of extrahepatic manifestations of autoimmune origin; and is a potentially fatal disease for which immunosuppressive treatment must be started early.
Assuntos
Autoanticorpos/análise , Doenças Autoimunes/imunologia , Hepatite/imunologia , Rim/imunologia , Fígado/imunologia , Microssomos/imunologia , Adolescente , Azatioprina/uso terapêutico , Criança , Pré-Escolar , Feminino , Hepatite/tratamento farmacológico , Anticorpos Anti-Hepatite B/análise , Antígenos de Superfície da Hepatite B/imunologia , Humanos , Lactente , Cirrose Hepática/imunologia , Masculino , Microssomos Hepáticos/imunologia , Prednisona/uso terapêutico , RecidivaRESUMO
An increasing number of reports indicate that patients with some inherited metabolic diseases may have symptoms resembling those of Reye syndrome. We describe two siblings who developed a Reye-like syndrome at ages 16 and 18 months, respectively, after a viral illness and salicylate therapy. Both had fasting hypoglycemia and hypoketonemia. At the time of the acute episode and after ingestion of a medium-chain triglyceride load, one of them excreted large amounts of abnormal metabolites derived from the omega- and (omega-1)-oxidation of medium-chain fatty acids. Medium-chain acyl-CoA dehydrogenase activity was lower than 20% of control values in fibroblasts from both patients. This enzyme defect should be considered in children with a Reye-like syndrome with these distinctive manifestations.
Assuntos
Acil-CoA Desidrogenases/genética , Síndrome de Reye/genética , Acil-CoA Desidrogenase , Acil-CoA Desidrogenases/deficiência , Acil-CoA Desidrogenases/urina , Glicemia/metabolismo , Caprilatos/sangue , Carnitina/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Feminino , Fibroblastos/enzimologia , Humanos , Lactente , Fígado/enzimologia , Fígado/patologia , Masculino , Síndrome de Reye/enzimologia , Síndrome de Reye/patologiaRESUMO
Seven children with juvenile rheumatoid arthritis had a syndrome characterized by hemorrhage and neurologic, hepatic, hematologic, and metabolic manifestations. The disease did not seem to conform clearly to the characteristics of Reye syndrome or any other well-known entity. This severe complication may be induced by macrophage activation secondary to a drug or intercurrent infection. Our data suggest that a sudden fall in erythrocyte sedimentation rate or in platelet and fibrinogen levels may mark the start of this complication and may be an indication for rapid steroid therapy.
Assuntos
Artrite Juvenil/fisiopatologia , Infecções Bacterianas/complicações , Coma/etiologia , Hemorragia/etiologia , Hepatopatias/etiologia , Doença Aguda , Artrite Juvenil/tratamento farmacológico , Aspirina/efeitos adversos , Criança , Pré-Escolar , Coma/fisiopatologia , Diagnóstico Diferencial , Feminino , Ouro/efeitos adversos , Hemorragia/fisiopatologia , Hepatomegalia/etiologia , Hepatomegalia/fisiopatologia , Humanos , Lactente , Hepatopatias/fisiopatologia , Masculino , Síndrome de Reye/diagnóstico , SíndromeRESUMO
Seventeen children with chronic active hepatitis and high serum titers of smooth-muscle or liver-kidney microsomal antibodies were given prednisone and azathioprine. Clinical and biochemical remission was obtained in all but two, who died of progressive liver failure. Evaluations in 14 children after a mean period of 22 months of treatment showed normal transaminase activity and gammaglobulin levels in 12, and serum autoantibody titers of less than 1: 100 in 10; liver histologic findings showed absence of inflammation in seven children, moderate portal or lobular inflammation in five, and minor features of aggressivity in two. Cessation of therapy was then attempted in nine children. Relapse occurred in all but one and could not be attributed to any previously recorded biologic or histologic feature. After follow-up of 18 months to 7 years, all but two patients are still receiving maintenance therapy with prednisone and azathioprine. Cirrhosis was present before treatment in 13 children and is now present in all but one. These results suggest that in most children with autoimmune chronic active hepatitis, immunosuppressive therapy can prevent further deterioration of liver function but must be pursued for several years before discontinuation is attempted.
Assuntos
Doenças Autoimunes/tratamento farmacológico , Hepatite Crônica/tratamento farmacológico , Imunossupressores/administração & dosagem , Adolescente , Doenças Autoimunes/patologia , Azatioprina/administração & dosagem , Criança , Pré-Escolar , Tolerância a Medicamentos , Feminino , Seguimentos , Hepatite Crônica/etiologia , Hepatite Crônica/patologia , Humanos , Lactente , Masculino , Prednisona/administração & dosagemRESUMO
We observed 45 children with a history of neonatal cholestasis associated with alpha 1-antitrypsin deficiency (phenotype PiZ). Twenty-five developed cirrhosis (group 1), and in the other 20, without cirrhosis (group 2), the outcome was considered to be good. Certain clinical, biochemical, and histologic features of each group were studied to permit early assessment of hepatic evolution. Liver biopsy showed that fibrosis was more frequent and severe in group 1 during neonatal cholestasis. Later this group was characterized by possible persistence of jaundice, early development of splenomegaly, and persistence of hard hepatomegaly and liver function abnormalities. Of the latter, sustained elevation of SGPT and direct bilirubin values were the most striking findings. The characteristics of group 2 were harder to identify: clinical recovery and return to normal biochemical values were always signs of a good outcome, as confirmed by the histologic findings; on the other hand, although some of the children in this group without cirrhosis had only minimal abnormalities, histologic evidence of significant portal fibrosis in some patients made long-term prognosis less certain.
Assuntos
Doenças do Recém-Nascido/diagnóstico , Hepatopatias/diagnóstico , Deficiência de alfa 1-Antitripsina , Colestase/diagnóstico , Feminino , Humanos , Recém-Nascido , Fígado/patologia , Cirrose Hepática/diagnóstico , Hepatopatias/patologia , Testes de Função Hepática , Masculino , Fenótipo , PrognósticoRESUMO
Four children, aged 6 1/2 months to 2 years, presented with liver disease and autoimmune hemolytic anemia. Clinical signs included fever, jaundice, firm or hard hepatomegaly, and splenomegaly. Direct Coombs test results were of the mixed (IgG + C) type. Liver function tests showed high direct bilirubin transaminase, and serum gamma globulin values, and a prolonged prothrombin time. The liver histology was characterized by marked lobular fibrosis and giant cell transformation. The course of the disease was severe, resulting in the death of three patients from liver failure. However, the liver disease seemed responsive to corticosteroid treatment, which in one patient was clearly beneficial.