Tag Archives: biliary atresia

Outcomes of Biliary Atresia

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A retrospective study from the Netherlands showed that timely surgery and postoperative antibiotics were associated with better outcomes in Biliary Atresia (BA) (J Pediatr 2012; 160: 638-44).  While these results are not surprising, due to the length of the study period (1987-2008) and the number of patients (n=214), the study offers insight into a number of unresolved issues with regard to BA.

The type of BA in this series:

  • type I      14  (6.5%)
  • type II      27 (12.6%)
  • type III   172 (80.4%)
  • undetermined  1 (0.9%)

Other notable findings:

  • 10% of their patients had splenic malformations; no significant change in outcome was noted in this subgroup.
  • 18% received high-dose corticosteroids –no benefit was identified in this subgroup.  The authors state that previous studies are inconclusive; a large US trial of prednisolone (4 mg/kg/day initially) is pending.
  • 31% received ursodeoxycholic acid –no benefit was identified in this subgroup.
  • Overall survival improved a little during the study period, mostly due to increased availability of liver transplantation. 4-year transplant-free survival was 46% and 4-year overall survival was 73%.   Table II (pg 641) in their study lists six other international studies.  Recent studies in some countries have reported 4-year survivals of 82-91%.
  • Antibiotic usage (most commonly co-trimoxazole) was associated with improved outcomes, presumably due to less frequent bouts of cholangitis.  Yet, in this study the reported incidence of cholangitis was not lower.  The authors do not have an explanation for this finding.

Age at time of Kasai:

  • ≤45 days 19%
  • 46-60 days 37%
  • 61-89 days 36%
  • ≥90 days 8%
  • Median was 59 days.  Authors note that Netherland guidelines call for all infants with jaundice at 3 weeks to have a fractionated bilirubin.

Related blog entries:

Minimizing malnutrition in Biliary Atresia

The heart connection

MicroRNAs and biliary atresia

Additional references:

  • -JPGN 2010; 51: 631.  n=91.  Operation w/in 100 days.  Data suggesting that 60 day cutoff is not valid. (Hong Kong)
  • -J Pediatr Surg 2003; 38: 997-1000. n=735.  90 day cutoff was key with 5-yr & 10-yr survival. (Japan)
  • -JPGN 2010; 51:61.  Canadian experience. n=230.  Center size did not affect outcome.  Overall 39% at 4yrs had survival with native liver.
  • -Liver transplantation 2009; 15: 829, 876.  With combo of Kasai & Tx, >95% exteneded survival (previously 100% fatal).  >80% will need a liver Tx at some point –~50% before age 2.  Increased fibrosis & genes for fibrosis may increase risk for poor outcome.
  • -JPGN 2009; 48: 72.  Review of 13 year experience. n=91.
  • -Pediatrics 2008; 121: e1438.  Single center (Australia?) noted longer delay in dx of BA over 15-year period from 48.5 days (1990-94) to 59.5 (95-99) to 69 days (2000-2004).
  • -JPGN 2008; 46: 238, 299.  More data on age of dx of BA and outcomes from Sweden.
  • -J Pediatr 2006; 149: 393.  Long term outcome of BA -28yrs in England.  7/56 survived long term with native liver; 5-yr native liver survival was 46%, 10-yr was 32%.
  • -J Pediatr 2006; 148: 467, 432..  Outcome of BA in US.  Avg age of referral was 53 days and HPE avg at 61 days.  one-third will survive to age 10 with native liver; overall 90% survival with kasai/hpe & Tx; 50-60% clear jaundice p Kasai.  yellow alert campaign: www.childliverdisease.org/jaundice
  • -Clin Gastro & Hep 2006; 1411.  BA with choledochal cyst. Nice pics of types of BA. Japanese pathologic classification:  Type 1 with atresia after gallbladder (CBD), type II atresia of common hepatic duct/CBD/GB  c normal intrahepatic ducts, Type III atresia of entire ductal system.
  • -Pediartics 2006; 117: 1147.  Usefulness of stool color cards for screening program.
  • -J Pediatr 2005; 147: 142 & 180-5.  23% c BA survive c native liver for more than 20 yrs; 88% survival for 3 yrs p-OLT; risk factors for poor outcome discussed including poor nutrition & age <5 months.
  • -J Pediatr 2004; 144: 123-5.  severity of fibrosis at time of Kasai inversely correlated with survival
  • -JPGN 2003; 37: 430-33.  Residual fibrosis/cirrhosis noted in 54%/40% respectively of pts with normal labs, median age 13 yrs.
  • -JPGN 2003; 37: 4-21. Review of BA

MicroRNAs and biliary atresia

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The human genome may encode over 1000 microRNAs (miRNAs), which may target about 60% of mammalian genes and are abundant in many human cell types. MicroRNAs are a class of short (18-23 nucleotide) noncoding RNA molecules which act as a negative regulator of target mRNA stability and translation.  This month the interaction of miRNAs with biliary atresia is examined (JPGN 2012; 54: 186-92).

Using a mouse model, the authors identify miRNA-29 overexpression associated with the downregulation of two mRNA targets related to biliary atresia pathogenesis.  The research has several limitations, including the use of adult mice.  The reason why I highlight this study is that miRNAs are helping elucidate basic disease mechanisms and identifying new therapeutic targets.  Some of these same investigators published “Circulating microRNA is a biomarker of pediatric Crohn disease.” (JPGN: 2011;  53(1): 26-33).  In this study, 11 CD-associated serum miRNA were identified with encouraging diagnostic potential.  These specific miRNAs were found in Crohn disease patients but not in controls and patients with celiac disease.  The sensitivity for Crohn disease was over 80%.

Despite this intriguing research, it not clear whether or when miRNAs will have an important role in bedside management.

Additional references:

The heart connection

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Cardiac changes with biliary atresia (BA) are surprisingly common– Gastoenterology 2011; 141: 1264-72.  In this study, 48 patients with BA, listed for liver transplantation, underwent echocardiography between 2004-2010.  The median age was 8 months.  Significant increases in left ventricle wall thickness (23% increase) and mass (51% increase) were noted; in addition, functional changes were noted as there was an increase in LV shortening fraction (8% increase).  Features of ‘cirrhotic cardiomyopathy’ were evident in 72% of infants (29/40).  The authors conclude that these heart changes likely contribute to prolongation of posttransplant hospitalization.

Additional References:

  • -J Am Coll Cardiol 2010; 56: 539-49
  • -J Hepatol 2010; 53: 179-90.

Minimizing malnutrition in Biliary Atresia

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A retrospective study in Liver Transplantation reviews a single center experience with the use of parenteral nutrition (PN) in patients with end-stage liver disease due to biliary atresia (Liver Transpl 2012; 18: 121-129).  In this study which spanned the past twenty years, 25 PN BA patients were compared to 22 non-PN BA patients –all patients were younger than 36 months.  PN was started when maximal enteral nutrition failed to improve markers of malnutrition (triceps skinfold thickness, & mid-arm circumference).  Among the PN BA patients, there was a higher gastrointestinal bleeding rate and ascites; however, there was no difference in the rates of bacteremia, length of intensive care unit stay after liver transplantation, or patient/graft survival.  The authors speculate that the outcome for the PN BA patients would have been much worse without the PN as malnourished BA patients are at increased risk for graft failure and post-transplant complications.  It is noteworthy that PN patients did have progression of their liver disease that seemed to accelerate with the administration of PN, perhaps due to PN-associated cholestasis.  Specific changes included higher bilirubin levels, lower platelet counts, worsened coagulopathy, and higher calculated PELD scores.

Additional References:

  • Hepatology 2007; 46: 1632-38.  Growth failure and outcomes in infants with BA.
  • J Pediatr 2005; 147: 180-85.  Outcomes of 755 BA patients listed for liver transplantation.