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LA
CONSULTA SEMANAL
DICIEMBRE
2000
CONSULTA
Arq
Gastroenterol 1999 Oct-Dec;36(4):185-94
[Prolonged neonatal cholestasis: prospective study].
Prado ET, Araujo M de F, Campos JV
Departamento de Pediatria da Faculdade de Ciencias Medicas da Santa Casa
de Sao
Paulo-FCMSCSP.
Due to the urgency in choosing either clinical treatment or immediate
surgical
intervention, the study of the prolonged neonatal cholestasis involves two
basic
aims: the differential diagnosis between biliary atresia and neonatal
hepatitis
and the research into the associated etiological agents. So, in a
prospective
trial carried out in the 70's, 77 children with prolonged neonatal
cholestasis
were studied in order to establish the differential diagnosis between
biliary
atresia and neonatal hepatitis, followed by the evaluation of 108 children
towards a pathogenesis of the prolonged neonatal cholestasis. The results
of the
differential diagnosis showed that within 18 items examined only 8 proved
to be
good biliary atresia indicators. They are as follows (in decreasing
order):
ductular proliferation (portal tracts), fibrosis (portal tracts),
cholestasis
(portal tracts), stools colour--acholia, hepatomegaly, canalicular
cholestasis
(lobule), infiltrate (portal tracts), giant cells (lobule). These eight
items
were then gathered in a sole indicator of great discriminative power, with
a
confidence level of 99%. The figures regarding the pathogenesis are:
rubella
virus 0%, herpes simplex virus 0%, listeriosis 0%, cytomegalovirus 2.2%,
hepatitis B virus 2.4%, toxoplasmosis 2.8%, alpha-1-antitrypsin deficiency
13.1%, syphilis 21.1%, autoantibodies against the liver 58.4%. Such work
thus
revealed that those eight most important factors when differentiating
biliary
atresia from neonatal hepatitis remain as fundamental indicators and, when
employed alongside other diagnostic methods, can help in the assembling of
a
multifactorial strategy less and less invasive and more precise. The
pathogenic
study, with its heavy dependency on time and place, has become more
complete with the introduction of new diagnostic methods, evolving to the ideal
progressive reduction of idiopathic processes.
J Pediatr Surg 2000 Apr;35(4):545-9
The role of endoscopic retrograde cholangiopancreatography in infants with
cholestasis.
Iinuma Y, Narisawa R, Iwafuchi M, Uchiyama M, Naito M, Yagi M, Kanada S,
Otaki
M, Yamazaki S, Honma T, Motoyama H, Baba Y
Department of Pediatric Surgery, Niigata University School of Medicine,
Niigata
City, Japan.
BACKGROUND/PURPOSE: Endoscopic retrograde cholangiopancreatography (ERCP)
was
assessed in the diagnosis of cholestatic liver disease in infants.
METHODS: ERCP
was performed in 50 infants who had prolonged cholestasis. Their ages
ranged
from 25 to 274 days (mean, 69 days), and their weight ranged from 2.6 to
6.7 kg
(mean, 4.7 kg). Incomplete visualization of the biliary tree or
visualization of
only the pancreatic duct was followed by exploratory laparotomy. In those
in
whom the biliary tree was visualized completely, the caliber of the bile
duct
was compared with that of the pancreatic duct. RESULTS: ERCP was completed
in 43
patients (success rate, 86%) without complications. In the 7 patients in
whom
ERCP failed, 6 had biliary atresia (BA) diagnosed by exploratory
laparotomy. The
other patient had congenital biliary dilatation (CBD). In 29 of the 43
patients,
the biliary tree was seen partially or only the pancreatic duct was
visualized.
These patients had BA diagnosed by laparotomy. Complete visualization of
the
biliary tree was obtained in 14 patients. Of these, 9 had neonatal
hepatitis
(NH), 2 had a paucity of intrahepatic bile ducts (PIBLD), and 3 had CBD.
In all
of the patients with NH, cholestasis improved spontaneously. The 2
patients with
PIBLD had biopsy-proven disease. The caliber of the bile duct was larger
than
that of the pancreatic duct in NH. This relationship was not observed in
PIBLD.
CONCLUSIONS: ERCP is safe in infants. It is useful in the diagnosis of
prolonged
cholestasis.
Clin Nucl Med 1999 Sep;24(9):655-9
The use of hepatocyte extraction fraction to evaluate neonatal
cholestasis.
Tolia V, Kottamasu SR, Tabassum D, Simpson P
Department of Pediatrics, Children's Hospital of Michigan, Detroit, USA.
vtolia@med.wayne.edu
PURPOSE: Hepatobiliary scintigraphy is used routinely to evaluate infants
with
neonatal cholestasis. Hepatobiliary scintigraphy determines biliary
patency by
detecting radioactivity in the bowel on imaging, in duodenal and gastric
aspirates, or all of these. During hepatobiliary scintigraphy, the
hepatocyte
extraction fraction (HEF) is calculated by deconvolution analysis. Normal
values of HEF are more than 90%. It is believed that HEF may predict hepatic
dysfunction, because, during hepatobiliary scintigraphy, the
radiopharmaceutical
used in this test is extracted by the hepatocytes from the blood stream.
Therefore, a low value of HEF is seen with more severe hepatocellular
disease.
The goal of this study was to determine whether HEF has any correlation
with
synthetic liver function, whether HEF can differentiate obstructive from
nonobstructive lesions that cause neonatal cholestasis, and whether HEF
can
predict the outcome of the different causes of neonatal cholestasis.
METHODS: A
retrospective analysis of 68 hepatobiliary scintigraphy results was done
in
patients with neonatal cholestasis for a period covering 6 years. RESULTS:
The
HEF was available in 67 of these 68 patients, with a median value of 25%
(range,
3.3% to 100%). The results of synthetic liver function tests (i.e.,
albumin and
prothrombin time) were normal in all infants with neonatal cholestasis. No
significant correlation was detected between HEF and the serum levels of
total
and direct bilirubin, albumin, alkaline phosphatase, and prothrombin time
by
exploratory data analysis (R = 0.08; small, P > 0.2). The HEF values in
different causes of neonatal cholestasis were compared: extrahepatic
biliary
atresia, neonatal hepatitis, and a miscellaneous category consisting of
alpha1-antitrypsin deficiency, ischemic hepatitis, paucity of bile ducts,
and
others. The outcomes of these diseases were assessed as resolution,
continuing
disease, transplantation, or death, but no predictive correlation was
found with
HEF. CONCLUSIONS: A single determination of HEF is of no value in
assessing
synthetic liver function (as assessed by albumin and prothrombin time),
specific
diagnoses, and outcomes in patients with neonatal cholestasis. Therefore,
a low
isolated value of HEF should not be considered suggestive of poor
prognosis and
outcome in these patients.
BMJ 1999 Aug 21;319(7208):B [Texto
completo]
Single screening test for neonatal cholestasis is not yet feasible from
blood
spots.
BMJ 1999 Aug 21;319(7208):471-7 [Texto
completo]
Published erratum appears in BMJ 1999 Nov 6;319(7219):1253
Screening of newborn infants for cholestatic hepatobiliary disease with
tandem
mass spectrometry.
Mushtaq I, Logan S, Morris M, Johnson AW, Wade AM, Kelly D, Clayton PT
Biochemistry Unit, Institute of Child Health, University College London,
London
WC1N 1EH.
OBJECTIVE: To assess the feasibility of screening for cholestatic
hepatobiliary
disease and extrahepatic biliary atresia by using tandem mass spectrometry
to
measure conjugated bile acids in dried blood spots obtained from newborn
infants
at 7-10 days of age for the Guthrie test. SETTING: Three tertiary referral
clinics and regional neonatal screening laboratories. DESIGN: Unused blood
spots
from the Guthrie test were retrieved for infants presenting with
cholestatic
hepatobiliary disease and from the two cards stored on either side of each
card
from an index child. Concentrations of conjugated bile acids measured by
tandem
mass spectrometry in the two groups were compared. MAIN OUTCOME MEASURES:
Concentrations of glycodihydroxycholanoates, glycotrihydroxycholanoates,
taurodihydroxycholanoates, and taurotrihydroxycholanoates. Receiver
operator
curves were plotted to determine which parameter (or combination of
parameters)
would best predict the cases of cholestatic hepatobiliary disease and
extrahepatic biliary atresia. The sensitivity and specificity at a
selection of
cut off values for each bile acid species and for total bile acid
concentrations
for the detection of the two conditions were calculated. RESULTS: 218
children
with cholestatic hepatobiliary disease were eligible for inclusion in the
study.
Two children without a final diagnosis and five who presented at <14
days of age were excluded. Usable blood spots were obtained from 177 index children
and 708
comparison children. Mean concentrations of all four bile acid species
were
significantly raised in children with cholestatic hepatobiliary disease
and
extrahepatic biliary atresia compared with the unaffected children
(P<0.0001).
Of 177 children with cholestatic hepatobiliary disease, 104 (59%) had a
total
bile acid concentration >33 micromol/l (97.5th centile value for
comparison
group). Of the 61 with extrahepatic biliary atresia, 47 (77%) had total
bile
acid concentrations >33 micromol/l. Taurotrihydroxycholanoate and total
bile
acid concentrations were the best predictors of both conditions. For all
cholestatic hepatobiliary disease, a cut off level of total bile acid
concentration of 30 micromol/l gave a sensitivity of 62% and a specificity
of
96%, while the corresponding values for extrahepatic biliary atresia were
79%
and 96%. CONCLUSION: Most children who present with extrahepatic biliary
atresia
and other forms of cholestatic hepatobiliary disease have significantly
raised
concentrations of conjugated bile acids as measured by tandem mass
spectrometry
at the time when samples are taken for the Guthrie test. Unfortunately the
separation between the concentrations in these infants and those in the
general
population is not sufficient to make mass screening for cholestatic
hepatobiliary disease a feasible option with this method alone.
Publication Types:
Multicenter study
J Pediatr Endocrinol Metab 1999 Jul-Aug;12(4):549-53
Parenteral nutrition-associated cholestasis in preterm neonates:
evaluation of
ursodeoxycholic acid treatment.
Levine A, Maayan A, Shamir R, Dinari G, Sulkes J, Sirotta L
Division of Gastroenterology and Nutrition, Schneider Children's Medical
Center
of Israel, Petah Tikva, Israel.
BACKGROUND/OBJECTIVE: Parenteral nutrition is an integral part of the care
of
premature infants. Cholestatic liver disease is a frequent complication of
prolonged parenteral nutrition, especially in premature infants. It has
been
suggested that ursodeoxycholic acid may alter the course of parenteral
nutrition-associated cholestasis in children and adults. We attempted to
determine the efficacy of ursodeoxycholic acid in premature infants with
parenteral nutrition-associated cholestasis. METHODS: Retrospective chart
review
of all infants receiving ursodeoxycholic acid for parenteral
nutrition-associated cholestasis in a 40 bed neonatal intensive care unit.
Efficacy of ursodeoxycholic acid was evaluated by response of bilirubin,
alanine
aminotransferase, aspartate aminotransferase, and alkaline phosphatase
over a
treatment period of at least 1 month. RESULTS: Six infants with parenteral
nutrition-associated cholestasis who had received ursodeoxycholic acid for
one
month were identified. Doses of ursodeoxycholic acid ranged from 15-30
mg/kg/day. Cholestasis appeared at a mean age of 47 +/- 17 (mean +/- SD)
days
after a mean of 42 +/- 15 days of parenteral nutrition. Transaminase
levels
decreased in three, and either increased or did not change in the other
three
infants. Bilirubin levels decreased in all infants. Alkaline phosphatase
showed
a non significant trend to decreased levels. Consistent improvement in all
infants was noted only after 10 days of full enteral nutrition. No
toxicity was
found during ursodeoxycholic acid treatment. CONCLUSIONS: Ursodeoxycholic
acid
treatment in premature infants appears to be safe, and leads to an early
sustained decrease in bilirubin levels by two weeks of therapy. The
response of
transaminase levels was not sustained in our small cohort.
J Pediatr 1999 Jun;134(6):795 [Texto
completo]
Transient neonatal cholestasis and perinatal asphyxia.
Vajro P, Paludetto R, DeCurtis M
Publication Types:
Comment
Letter
Comments:
Comment on: J Pediatr 1998 Oct;133(4):563-7
J Pediatr 1998 Oct;133(4):563-7
Transient neonatal cholestasis: origin and outcome.
Jacquemin E, Lykavieris P, Chaoui N, Hadchouel M, Bernard O
Departement de Pediatrie, Hopital de Bicetre, Le Kremlin Bicetre, France.
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.
Comments:
Comment in: J Pediatr 1999 Jun;134(6):795
Braz J Med Biol Res 31( 7) 1998 [Texto
completo en formato PDF]
Histological diagnosis of neonatal cholestasis Brazilian Journal of
Medical
and Biological Research (1998) 31: 911- 919 ISSN 0100- 879X
Histopathological diagnosis of intra-and extrahepatic neonatal cholestasis
Departamentos de 1 Pediatria, 2 Cirurgia and 3 Patologia, Universidade
Federal
do Rio Grande do Sul, Porto Alegre, RS, Brasil J. L. Santosą, H. Almeida˛,
C.
T. S. Cerski 3 and T. R. Silveira
The histopathology of the liver
is
fundamental for the differential diagnosis between intra- and extrahepatic
causes of neonatal cholestasis. However, histopathological findings may
overlap
and there is dis-agreement among authors concerning those which could
discriminate
between intra- and extrahepatic cholestasis. The most valuable hepatic
histopathological variables for the dis-crimination between intra- and
extrahepatic
cholestasis, in decreasing order of importance, were periportal
ductal
proliferation, portal ductal proliferation, portal expansion, cholestasis
in
neoductules, foci of myeloid metaplasia, and portal- portal bridges.
References
Data indicating EHC Data indicating IHC Kasai et al. (25) Portal fibrosis,
portal
ductal proliferation, More marked hepatocytic degenerative neoductule
cholestasis,
Kupffer cell alterations and giant cell transformation cholestasis, severe
portal
expansion, marked lobular fibrosis with disarray of the lobular
architecture even
before the age of 6 months Present study Periportal ductal proliferation,
Foci of
myeloid metaplasia portal ductal proliferation, portal expansion,
cholestasis in neoductules, portal cholestasis, portal- portal bridges
Indian Pediatr 1996 Sep;33(9):753-62
Neonatal cholestasis syndrome in India--a diagnostic and therapeutic
challenge.
Bhave SA, Bavdekar AR, Pandit AN
Department of Pediatrics, K.E.M. Hospital Research Center, Pune.
Indian Pediatr 1996 Sep;33(9):729-34
Neonatal cholestasis syndrome: an appraisal at a tertiary center.
Yachha SK, Khanduri A, Kumar M, Sikora SS, Saxena R, Gupta RK, Kishore J
Department of Gastroenterology (Pediatric GE), Sanjay Gandhi Post Graduate
Institute of Medical Sciences, Lucknow.
OBJECTIVE: To know the magnitude, etiology and clinical profile, the
efficacy of
various investigations and the outcome in patients with neonatal
cholestasis
syndrome (NCS). DESIGN: Prospective evaluation of 60 consecutive infants
with
NCS (mean age 3.9 +/- 1.9 months; 49 males) over a period of 3.5 years.
SETTING:
Tertiary level referral gastroenterology center in North India. METHODS:
Liver
function tests, urine examination, serum antibodies against
Cytomegalovirus
(CMV), Rubella and Toxoplasma; abdominal ultrasonography, hepatobiliary
scintigraphy and liver biopsy were done. In appropriate setting,
laparotomy and
surgical corrections were done for biliary tract disorders. RESULTS: NCS
constituted 19% of pediatric liver diseases. Considerable delay in
presentation
was observed [mean delay, extrahepatic biliary atresia (EHBA) = 4 +/- 2.0
months, neonatal hepatitis (NH) = 2.2 +/- 1.3 months]. Thirty three (55%)
infants had EHBA, 14 (23%) NH (4 CMV, 2 galactosemia, 1 urinary tract
infection
and 7 idiopathic), 2 (3%) paucity of intralobular bile ducts and 11 (18%)
were
of indeterminate etiology. Liver biopsy was the most accurate (96.4%)
investigation in discriminating between EHBA and NH. Of the 18 operated
infants
with EHBA (portoenterostomy-15 and hepatico-jejunostomy-3), 10 were alive
(mean
follow up = 22.8 +/- 8.6 months) of which 4 were completely asymptomatic.
CONCLUSIONS: (i) NCS is an important cause of liver disease in Indian
children.
(ii) It requires prompt referral, quick investigative approach and
targeted
management. (iii) Liver biopsy is highly accurate in differentiating EHBA
and
NH. (iv) infants with EHBA and compensated status of liver should undergo
corrective surgery irrespective of age at presentation.
Clin Perinatol 1996 Jun;23(2):321-52
Neonatal hepatobiliary disorders.
Andres JM
Department of Pediatrics, University of Florida College of Medicine,
Shands
Hospital, Gainesville, USA.
Neonatal hepatobiliary disorders are now better understood due primarily
to new
discoveries in molecular genetics, virology, and immunology. Because they
are
almost always pathologic and require early intervention, the neonatologist
must
recognize infants with these hepatocellular and ductal cholestatic
problems
occurring in the first few weeks of life. This article focuses mainly on
new
developments regarding neonatal metabolic disorders and their potential
for gene
therapy; perinatal infections, especially those caused by hepatitis B
virus,
hepatitis C virus, and human immunodeficiency virus; and recent concepts
of
neonatal hepatitis and biliary atresia, including a review of predictors
that
influence outcome for infants undergoing Kasai portoenterostomy and liver
transplantation.
Publication Types:
Review
Review, tutorial
Trop Gastroenterol 1996 Apr-Jun;17(2):61-9
Neonatal cholestasis.
Arora NK
Department of Paediatrics, AIIMS, New Delhi.
Publication Types:
Review
Review, tutorial
Rev Gastroenterol Peru 1995 Jan-Apr;15(1):27-33
[Neonatal cholestasis in the Children's Health Institute: evaluation of
obstructive cholangiopathy syndrome in children].
Rivera-Medina J, Aguado-Quevedo R, Rodriguez-Huapaya J, Palacios-Salas M,
Gonzales-Benavides J, Alarcon-Olivera A
Servicio de Gastroenterologia, Instituto de Salud del Nino.
In order to establish a clinical or laboratory difference 52 Clinical
charts of
patients that were attended at the Gastroenterologic Unit at the
Children's
Hospital in Lima-Peru since January 1988 to December 1992, with the
diagnosis of
Neonatal Cholestasis were reviewed. 14 of them were discharged; at the end
we
have reviewed 23 cases of biliary atresia, 8 of neonatal hepatitis and 7
with
congenital choledochal cyst. All patients went through sonography,
scintigraphy
and liver biopsy. No statistical differences were found in symptomatology,
as
well as jaundice, feces color or coluria. We concluded that the most
accurate
way to predict a diagnosis is through the sonography, scintigraphy and
liver
biopsy.
Pediatr Clin North Am 1994 Oct;41(5):943-66
Neonatal cholestasis. New approaches to diagnostic evaluation and therapy.
Shah HA, Spivak W
Department of Pediatrics, Montefiore Medical Center, Albert Einstein
College of
Medicine, Bronx, New York.
Neonatal cholestasis remains a major diagnostic challenge despite
increasing
knowledge regarding its pathogenesis. The time constraint and urgency in
the
investigational process is underscored by the age-dependent success rate
of the
surgical corrective procedures for EHBA. Appropriate interpretation of
imaging
and pathologic studies requires a pediatric center familiar with the
entities
causing neonatal cholestasis. When liver failure or progressive hepatic
dysfunction is likely to occur, early referral to a liver transplant
center is
recommended. Despite the increasing experience and excellent results of
pediatric liver transplantation, at this point, surgical corrective
procedures
such as the Kasai procedure remain the first line of treatment for most
patients
with EHBA.
Publication Types:
Review
Review, academic
J Pediatr 1994 Sep;125(3):379-84
A new cause of progressive intrahepatic cholestasis: 3
beta-hydroxy-C27-steroid
dehydrogenase/isomerase deficiency.
Jacquemin E, Setchell KD, O'Connell NC, Estrada A, Maggiore G, Schmitz J,
Hadchouel M, Bernard O
Department of Pediatrics, Hopital de Bicetre, Le Kremlin Bicetre, France.
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.
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