โรคทางเดินน้ำดีตีบตัน biliary atresia 2018.pdfbasm...
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Biliary Atresiaโรคทางเดินน้ําดีตนั
Paisarn Vejchapipat, et al.
Department of Surgery, Faculty of MedicineChulalongkorn University, Thailand
Disclosure
None
Background
• Biliary atresia (BA) is characterized by inflammatory obstructive cholangiopathy of unknown origin, occurring in the perinatal period
• BA is the main cause of cholestatic jaundice in neonates with the incidence of 1:5,000-15,000
• If left untreated, the condition will lead to cirrhosis and death within the first two years
• BA is the most common ‘surgical’ cause of jaundice in infancy
• Surgical treatment usually involves two steps – Kasai operation (hepatic porto-enterostomy)
performed in infants– Subsequent liver transplantation if needed
• BA is the main indication for liver transplantation in infants and children
Background
Thailand
• Statistics in 2014
• Population: ≈66 million
• Pediatric: ≈12 million
• Births: ≈700,000 /year
Department of Provincial AdministrationMinistry of Interior
Etiology
• The etiology remains unsolved
• There are several hypotheses including– Occult viral infections– Immune-mediated injury– Maternal microchimerism– Ductal plate malformation– Pancreatico-biliary maljunction
Pathology• Various stages of inflammation causing progressive
destruction of the bile duct both intra- and extrahepatic
• Portal fibrosis and bile duct proliferation are pathognomonic
Hepatic iNOS Expression in BA
• Strong hepatic iNOS expression in BA patients• In BA, hepatocyte is likely to be the major source of
nitric oxide production
Vejchapipat P, et al. Hepatol Res 2008
Morphological Classification
95%
5%
Phenotypic classification
• Isolated BA
• Cystic BA (10%)
• CMV associated BA (10%)
• BA splenic malformation (BASM) syndrome
Davenport M. Neonatal Surgery 2018
Cystic BA
Report of Cystic Biliary Atresia
An unusual type of Biliary AtresiaSookpotarom P, Vejchapipat P. Eur J Pediatr Surg 2007
Effect of cystic change in BA
Davenport M. Diseases of the Liver and Biliary System in Children 2017
Recognized anomalies in the BASM syndrome
Davenport M, et al. Surgery of the Liver, Bile Ducts and Pancreas in Children 2017
True survival in BA and other anomalies versus isolated BA
Davenport M. Diseases of the Liver and Biliary System in Children 2017
Clinical Presentation
• Jaundice, acholic stools, dark urine and hepatomegaly
Diagnosis
• Symptoms and signs
• Conjugated hyperbilirubinemia
• Ultrasonography
• Hepatobiliary scintigraphy
• Intra-operative cholangiography
U/S: Triangular cord sign
The diagnosis of BA
• Babies (0-4 months old) with cholestatic jaundice and persistent acholic stools
Ultrasound
Triangular cord sign +ve IOC
Triangular cord sign –ve
IOC (age> 60days)
DISIDA (age <60days)
Choledochalcyst Surgery
Intra-operative Cholangiography
Biliary Atresia Non-BA
IOC of BA
• Most of the BA patients (95%) had atresia at portahepatis (type III)
• BA type III with patent cystic duct and common bile duct were found 23% in our series
Treatment
Prof. Morio Kasai Hepatic Portoenterostomy 1955
Kasai operation
J Pediatr Surg 2012;47:1023-7
Kasai M. J Pediatr Surg 1968
Kasai operation
Operative Findings
Small gall bladderCholestatic liver
Hepatic Portoenterostomy (Kasai Operation)
Dissection of Porta Hepatis
Small GB
Round ligament
Hepatic artery
Portal vein
Enlarged LN
GB fossa
Hepatic Portoenterostomy (Kasai Operation)
Hepatic Portoenterostomy(Kasai Operation)
Outcome of Kasai operation
• Good outcome (40-60%)– Jaundice-free, yellow stool, TB < 2 mg%– Survival > 5 years
• Fair outcome (20-30%)– Decreased Jaundice, yellow stool, but TB > 2 mg%– Survival > 3 years
• Poor outcome (20-30%)– Increased Jaundice and signs of chronic liver disease– Survival < 3years
Grosfeld et al. Surgery 1989
Prof. Mark Davenport (King’s College London)@ Annual Meeting of Royal College of Surgeons of Thailand 2009
Davenport M, et al. Surgery of the Liver, Bile Ducts and Pancreas in Children 2017
59
True and native liver survival curves for BA (n=443) in England and Wales (1999–2009)
Diseases of the Liver and Biliary System in Children 2017
Factors Affecting The Outcome
• The age at the time of operation
• The status of the liver
• Phenotypic classification
• The size of bile canaliculi at porta hepatis
• Surgeons’ experience
• Patient load per year at that centre
Effect of age at Kasai operation
Davenport M, et al. Surgery of the Liver, Bile Ducts and Pancreas in Children 2017
CMV-associated BA vs. native liver survival
Complications
• Ascending cholangitis (30-60%)
• Portal hypertension (34-76%)
• Hepato-pulmonary syndrome
• Intrahepatic biliary cysts
Chulalongkorn’s Experience• 1986-1995:
– 115 cases– Chula Med J 1996
• 1996-2001:– 92 cases– Asian J Surg 2005
• 2002-2005:– 53 cases– J Pediatr Surg 2007
• 2006-2014:– 89 cases– Pediatr Surg Int 2016 Chulalongkorn University
Age at The Time of Surgery
AGE
210.0200.0
190.0180.0
170.0160.0
150.0140.0
130.0120.0
110.0100.0
90.080.0
70.060.0
50.040.0
30.0
16
14
12
10
8
6
4
2
0
Std. Dev = 36.44 Mean = 90.3N = 92.00
(days)
No.
ofpa
tient
s
Only 23% had Kasai operation before 60 days of age63% operated before 90 days of ageMedian age of surgery = 88 days
Sookpotarom et al. Asian J Surg 2005
Cases/year
Clearance of jaundice within 6 months after Kasai Operation
38%
50.7%56.6% 58.3%
The Effects of Post-op Steroids
• The use of high-dose post-op steroids is controversial
• 53 BA patients over 4 years
• Steroids did not statistically improve early outcome in BA– Jaundice-free: 61% vs. 50% (steroid vs. non-steroid)
Vejchapipat P, et al. J Pediatr Surg 2007
The Effects of Post-op Steroids
Chusilp S, et al. Pediatr Surg Int 2016
1-year survival 85%3-year survival 70%5-year survival 65%
Chusilp S, et al. Pediatr Surg Int 2016
P=0.0215
Chusilp S, et al. Pediatr Surg Int 2016
Good outcome group Poor outcome group5-year survival 96% 36%
HR 0.05
95%CI 0.01-0.15
P <0.001
Chusilp S, et al. Pediatr Surg Int 2016
Circulating E-Selectin in Biliary Atresia
• Serum E-selectin of BA patients was higher than the controls
• There was an increase in serum E-selectin in BA patients with jaundice compared to those without jaundice
BA patients Controls0
100
200
BA, N=53Control, N=10
Seru
m s
E-se
lect
in(n
g/m
L)
P<0.01
Jaundice-free Jaundice0
100
200
Jaundice-free (N=32)Jaundice (N=21)
BA patientsSe
rum
sE-
sele
ctin
Mea
n+SD
(ng/
mL)
P=0.035
Vejchapipat P, et al. Eur J Pediatr Surg 2008
Serum TGF-β1 and EGF in BA
Vejchapipat P, et al. Eur J Pediatr Surg 2008
Good outcome Poor outcome0
50
100
Seru
m T
GF-β
1(n
g/m
l)
P=0.002
N=40 N=27
Good outcome Poor outcome0
50
100
150
200
250
Seru
m E
GF
(pg/
mL)
P=0.02
N=40 N=27
BA patients with good outcome had serum TGF-β1 and EGF higher than those with poor outcome
Systemic nitric oxide production was elevated in BA
Control BA0
50
100
Subjects
µ mol
/L (m
ean+
SD)
P=0.001
N=12 N=65
Vejchapipat P, et al. Pediatr Surg Int 2006
The fate of biliary atresiaBiliary atresia
Kasai operation
Transplantation
Poor outcome Good outcome
Short-term~40% ~60%
Deterioration Normal life
Long-term50% 50%
Roles of Liver Transplantation
• Patients with decompensated liver cirrhosis at the time of referral
• Patients without bile drainage after Kasai operation
• Patients with partial bile drainage with– Developmental retardation– Their sequelae become uncontrollable
• Primary liver transplantation is still controversial
Conclusions• Neonates or infants with direct hyperbilirubinemia
must be investigated to rule out biliary atresia
• Kasai operation is still the first therapeutic option for biliary atresia
• Liver transplantation is preserved for patients with failed Kasai or severe liver fibrosis
• Teamwork of healthcare providers is critical
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