Biliary Atresia

Biliary Atresia Diagnosis, Management protocols and Recent advances Dr Ravi Kanojia PGIMER, Chandigarh India

Objectives Spectrum of surgical jaundice How do we diagnose EHBA Pre op management by the surgical team Post op management Prognostic factors Follow up PGI experience Message and lessons learnt Recent advances in EHBA we will not be talking on Surgical details and options Liver transplant

Spectrum of surgical jaundice

How do we diagnose EHBA

Pre op management by the surgical team

Post op management

Prognostic factors

Follow up

PGI experience

Message and lessons learnt

Recent advances in EHBA

we will not be talking on

Surgical details and options

Liver transplant

Common case scenario Term 60 days old female infant Jaundice since birth Passing pale white stools with mustard color urine Palpable firm hepatomegaly Referred by a Pediatrician after a exhaustive non conclusive work up spending precious prognostic days

Term 60 days old female infant

Jaundice since birth

Passing pale white stools with mustard color urine

Palpable firm hepatomegaly

Referred by a Pediatrician after a exhaustive non conclusive work up spending precious prognostic days

Surgical causes of jaundice Biliary atresia Choledochal cyst Bile duct perforation Inspissated bile syndrome

Biliary atresia

Choledochal cyst

Bile duct perforation

Inspissated bile syndrome

Alpha1-anti-trypsin deficiency Idiopathic neonatal hepatitis Algillie syndrome Inborn errors of bile acid synthesis Nonsyndromic intrahepatic bile duct hypoplasia Total parenteral nutrition–associated (TPN) cholestasis Viral infections (eg, toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex [TORCH]) Other Causes

Alpha1-anti-trypsin deficiency

Idiopathic neonatal hepatitis

Algillie syndrome

Inborn errors of bile acid synthesis

Nonsyndromic intrahepatic bile duct hypoplasia

Total parenteral nutrition–associated (TPN) cholestasis

Viral infections (eg, toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex [TORCH])

Diagnosis Clinical Suspicion by Prolonged jaundice Conjugated hyperbilirubinemia Acholic stools dark urine Firm to hard palpable hepatomegaly Antenatally by abnormal maternal usg Cyst in the porta Spleenic malformations

Clinical Suspicion by

Prolonged jaundice

Conjugated hyperbilirubinemia

Acholic stools dark urine

Firm to hard palpable hepatomegaly

Antenatally by abnormal maternal usg

Cyst in the porta

Spleenic malformations

Investigations Non invasive & Invasive Non invasive Biliary USG HIDA/Mebrofennin Scan MRCP Invasive Liver biopsy Per op cholangiogram Serial Duodenal intubations ERCP Laparoscopy Hematology Routine LFT Gamma GGT Sr Lipoprotien X TORCH Minimum recommended (PGI Practice) USG + HIDA (with priming) + hematology (>85% sensitive for pre op diagnosis) Per op cholangiogram

Investigations

Non invasive & Invasive

Non invasive

Biliary USG

HIDA/Mebrofennin Scan

MRCP

Invasive

Liver biopsy

Per op cholangiogram

Serial Duodenal intubations

ERCP

Laparoscopy

Hematology

Routine LFT

Gamma GGT

Sr Lipoprotien X

TORCH

Minimum recommended (PGI Practice)

USG + HIDA (with priming) + hematology (>85% sensitive for pre op diagnosis)

Per op cholangiogram

Biliary USG Triangular Cord Sign GB motility GB length Measure GB length remains same before and after feeding All the 3 factors combined gives positive predictive value of > 90% JPS (2007) 42, 2093–2096

Triangular Cord Sign

GB motility

GB length

HIDA Hepatobiliary excretion scans Pretreatment with phenobarb 5mg/kg/d for 3-5 days Simultaneous administration of UDCA may be done DISIDA – not reliable when sr bil levels are very high (>10) 99mTc-mebrofenin IDA Recent reports of technetium-99m-mebrofenin iminodiacetate scans combined with estimation of gama GGT increases the negative predictive value to > 80%

Hepatobiliary excretion scans

Pretreatment with phenobarb 5mg/kg/d for 3-5 days

Simultaneous administration of UDCA may be done

DISIDA – not reliable when sr bil levels are very high (>10)

99mTc-mebrofenin IDA

Recent reports of technetium-99m-mebrofenin iminodiacetate scans combined with estimation of gama GGT increases the negative predictive value to > 80%

MRCP Is done when usg demonstrates cysts at porta Reliably differentiates between choledochal cyst and cystic variants of EHBA

Is done when usg demonstrates cysts at porta

Reliably differentiates between choledochal cyst and cystic variants of EHBA

Liver Biopsy 90% sensitivity and specificity for biliary atresia. Biopsies are not usually diagnostic in those younger than 2 weeks Portal bile ductular proliferation, bile plugging, portal-portal fibrosis, and an acute inflammatory reaction Not our preferred practice because most of the patients coming late and have a deranged coagulogram and practical problems

90% sensitivity and specificity for biliary atresia.

Biopsies are not usually diagnostic in those younger than 2 weeks

Portal bile ductular proliferation, bile plugging, portal-portal fibrosis, and an acute inflammatory reaction

Not our preferred practice because most of the patients coming late and have a deranged coagulogram and practical problems

Per op cholangiogram Decision algorithm ? EHBA Laparotomy Bile in GB Aspirate GB if patent with lumen White bile Obtain Cholangiogram Proceed for Kasai Small non patent fibrotic GB EHBA confirmed

Decision algorithm

Duodenal Intubation Aspiration of duodenal contents via an endoscope Preferred Japanese practice Reliably rules out BA if bile is seen aspirate Sensitivity can be increased by combining with HIDA – if aspirated contents shows some radioactivity then BA is ruled out

Aspiration of duodenal contents via an endoscope

Preferred Japanese practice

Reliably rules out BA if bile is seen aspirate

Sensitivity can be increased by combining with HIDA – if aspirated contents shows some radioactivity then BA is ruled out

ERCP Pediatric scope looking for ampula of vater and trying for retrograde dye study Technical limitations are there with the scope as well as the skill No added advantages over other investigations

Pediatric scope looking for ampula of vater and trying for retrograde dye study

Technical limitations are there with the scope as well as the skill

No added advantages over other investigations

Laparoscopy Has a role in obtaining a POC with minimally invasive technique KPE procedure can be accomplished through it Major advantages offered are Magnification while dissecting at the porta Minimal adhesions at the time of liver transplant

Has a role in obtaining a POC with minimally invasive technique

KPE procedure can be accomplished through it

Major advantages offered are

Magnification while dissecting at the porta

Minimal adhesions at the time of liver transplant

Diagnosis pathway followed Clinical Suspicion (conjugated jaundice), acholic stools Hepatobiliary USG Hepatic nuclear excretion scans If no bilioenteric drainage POC and proceed

Pre op management protocol Physicians role Identify Conjugated jaundice + pale stools  go for USG followed by HIDA EARLY REFERAL

Physicians role

Identify

Conjugated jaundice + pale stools  go for USG followed by HIDA

EARLY REFERAL

Pre op management Phenobarbitone Vit k Antibiotics Nutrition

Phenobarbitone

Vit k

Antibiotics

Nutrition

Post operative management Supportive Pharmacological options improving outcomes Phenobarbitone UDCA Steroids Vitamin supplements Antibiotics

Supportive

Pharmacological options improving outcomes

Phenobarbitone

UDCA

Steroids

Vitamin supplements

Antibiotics

Role of steroids Basis Reduces inflamation Immune suppression Cholerectic action- increases canalicular electrolyte transport and stimulate bile flow independent of the bile salt concentration. With these basis it Decreases protal fibrosis Increased bile flow Decreasing cholangitis Our practice Not routinely prescribed In the event of cholangitis or persistent white stools 2mg/kg/d prednisolone

Basis

Reduces inflamation

Immune suppression

Cholerectic action- increases canalicular electrolyte transport and stimulate bile flow independent of the bile salt concentration.

With these basis it

Decreases protal fibrosis

Increased bile flow

Decreasing cholangitis

Our practice

Not routinely prescribed

In the event of cholangitis or persistent white stools 2mg/kg/d prednisolone

Prognostic factors Age at presentation Bile duct size at porta after excision of the fibrotic cord Liver histology at the time of KPE Presence of portal hypertension Associated malformations MAP Score JPS, Vol31, No 10,1996: pp 1387-1390

Age at presentation

Bile duct size at porta after excision of the fibrotic cord

Liver histology at the time of KPE

Presence of portal hypertension

Associated malformations

Follow up protocol Repeat LFT at 1 mth Repeat HIDA at 3 mth 3 monthly review subsequently Registration for LTx registry

Repeat LFT at 1 mth

Repeat HIDA at 3 mth

3 monthly review subsequently

Registration for LTx registry

Recent Advances Ductal plate malformation – aberrant morphological distribution of intrahepatic bile ducts seen using immunohistochemical staining for cytokeratin 19 (CK-19) in liver biopsy

Ductal plate malformation – aberrant morphological distribution of intrahepatic bile ducts seen using immunohistochemical staining for cytokeratin 19 (CK-19) in liver biopsy

Recent advances in molecular pathology Increased expression of ICAM AND VCAM molecules in the sinusoidal epithelium Now serum measurements of the molecules is possible Few candidate genes jagged 1 mutation CFC HNF-6 INV

Recent advances in molecular pathology

Increased expression of ICAM AND VCAM molecules in the sinusoidal epithelium

Now serum measurements of the molecules is possible

Few candidate genes

jagged 1 mutation

CFC

HNF-6

INV

PGI Experience 15 pt in single unit in 14 mth Age range 1-6 mth Mean age 87 days Mean bil levels 10.4 (range 6-17) Predominant usg findings Small contracted GB or gb not visualised Cysts at the porta HIDA scan Good hepatocyte uptake with absent billio enteric drainage

15 pt in single unit in 14 mth

Age range 1-6 mth

Mean age 87 days

Mean bil levels

10.4 (range 6-17)

Predominant usg findings

Small contracted GB or gb not visualised

Cysts at the porta

HIDA scan

Good hepatocyte uptake with absent billio enteric drainage

Atretic GB with complete atresia of the EHBT Ty IIA Extrahepatic cyst with proximal atresia Per op findings 12 1 2

Outcome (short term) All passed yellow stools after the procedure Persistent jaundice (levels les than pre op) Appetite increased Gaining weight Mortality none

Outcome (short term)

All passed yellow stools after the procedure

Persistent jaundice (levels les than pre op)

Appetite increased

Gaining weight

Mortality none

Lessons learnt Poor prognosis even after good bile flow Surgery improves quality of life in terms of feeding and thriving Prognosis does not has a marked difference with early v/s late operated patients Early sx reduces the incidence of complications, post op cholangitis, better response to drug treatment and delayed appearance of secondary PHT

Poor prognosis even after good bile flow

Surgery improves quality of life in terms of feeding and thriving

Prognosis does not has a marked difference with early v/s late operated patients

Early sx reduces the incidence of complications, post op cholangitis, better response to drug treatment and delayed appearance of secondary PHT

Kasai Portoenterostomy Video part 1

Video part 1

Kasai Portoenterostomy Video part 2

Video part 2

Kasai Portoenterostomy Video part 3

Video part 3

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