Expert Recommendations for ARPKD

A recent article (J Pediatr 2014; 165: 611-17) provides expert recommendations for the diagnosis and management of autosomal recessive polycystic kidney disease (ARPKD).

Some of the recommendations relevant to hepatologists:

  • Congenital hepatic fibrosis (CHF) “is presumed when portal HTN [hypertension] is present.”  Portal HTN is defined by splenomegaly (i.e.. spleen >2 cm below the left costal margin or >1 cm larger than ULN for age) and thrombocytopenia with a value of <150 mm3.  Other evidence of portal HTN includes varicose, ascites or hepatopulmonary syndrome.
  • “Liver biochemistries are not typically informative…one should monitor for associated neutropenia and thrombocytopenia.”
  • “Cholangitis may be difficult to diagnose definitively…should be considerd in any child with ARPKD with unexplained fever.” “Routine antibiotic prophylaxis is not indicated…antibiotic prophylaxis for 6-12 weeks after a cholangitis episode..may be considered.”
  • The “use of ursodeoxycholic acid as a choleric cannot be recommended.”
  • Hepatobiliary cancer is not a feature of ARPKD in children
  • “Limiting contact activities in individuals with a palpable spleen is highly controversial and not guided by evidence, but more by common sense.”
  • Recommends annual CBC, ultrasound at five years of age, and then follow-up ultrasound every 2-3 years.

Related blog post:

Outcome of “Successful” Biliary Atresia Patients

A recent publication (J Pediatr 2014; 165: 539-546) from the Childhood Liver Disease Research and Education Network (CHiLDREN) provides a strong rationale for close followup of biliary atresia (BA) patients with their native livers.  The Biliary Atresia Study of Infants and Children (BASIC) is one of the ongoing longitudinal studies within CHiLDREN.

Among a cross-sectional study BASIC cohort of 219 children (median age 9.7 years) who survived with their native livers for at least 5 years, they had the following findings:

  • In preceding 12 months, cholangitis occurred in 17%, and 62% had experienced cholangitis at least once following hepatoportoenterostomy (HPE) (also called Kasai procedure.  The authors note wide discrepancy in usage of prophylactic antibiotics; some stop at 2 years following HPE and some never stop antibiotic prophylaxis.
  • In preceding 12 months, bone fractures occurred in 5.5%.  Overall, 15% had had at least one bone fracture at some point, which is higher than the general population. Only 14.6% of entire cohort were receiving vitamin D supplementation.
  • Portal hypertension: clinically detectable splenomegaly, thrombocytopenia, ascites, and variceal hemorrhage were seen in 56%, 43%, 17%, and 9% of patients in this cohort.
  • Health-related quality of life was reported as normal in 53%
  • Mean height and weight z-scores were normal in this cohort.
  • Over 98% had clinical or biochemical evidence of chronic liver disease.

Full-text Link

Bottomline: This BASIC study shows the need for careful followup of “successful” biliary atresia patients and provides more accurate data regarding risks of specific complications.

Briefly noted: J Pediatr 2014; 165: 547-55.  In this study with same first author (Vicky Ng), the investigators develop and validate a pediatric liver transplantation (LT) quality of live instrument for LT patients aged 8-18 years.

Related blog posts:

What and When for ERCP with Gallstone Pancreatitis

A recent case vignette highlights several key points regarding use and timing of ERCP (endoscopic retrograde cholangiopancreatography) for gallstone pancreatitis (NEJM 2014; 370: 150-7). Figure 1 provides a nice illustration of ERCP.

Indications:  Suspected bile-duct stones as the cause of pancreatitis AND one of the following:

  • cholangitis (fever, jaundice, sepsis)
  • persistent biliary obstruction (conjugated bilirubine level >5 mg/dL)
  • clinical deterioration (worsening pain, increasing white cell count, worsening vital signs)
  • stone evident in the common bile duct on imaging

AGA position paper (2007):

  • Urgent ERCP (within 24 hours of admission) was recommended in those with cholangitis
  • Early ERCP (within 72 hours of admission) was recommended if suspicion of persistent bile-duct stones remained high

Patient information/animated videos for pancreatic diseases from the National Pancreas Foundation: http://ow.ly/sF9vb 

Related post:

Indomethacin to prevent post-ERCP pancreatitis | gutsandgrowth

Congenital hepatic fibrosis

In a previous blog entry (Hepatic ciliopathies), I briefly discussed congenital hepatic fibrosis (CHF).  A more detailed review and handy reference: Srinath A, Shneider BL. JPGN 2012; 54: 580-87.

This invited review details information related to 1230 CHF patients from 155 articles (available at http://links.lww.com/MPG/A88).  Median and mean age of diagnosis were 2 and 11.2 years respectively.

Distribution of CHF cases/associated conditions: 118 isolated CHF, 788 autosomal recessive polycystic kidney disease, 315 with Caroli disease/syndrome, 9 with type V choledochal cyst

Clinical problems:

  • Sequelae of portal hypertension in 409 patients: 164 with varices, 74 with bleeding varicose, 81 underwent portosystemic shunting.  Portal hypertension itself was identified in 71-97% depending on the patient subset examined.
  • Cholangitis in 152 patients –often recurrent.  This was fatal in 3 of 23 children after renal transplantation.
  • Malignancy in 21 patients (2%). 19 were cholangiocarcinoma.  Of these cases, 10/19 had Caroli disease/syndrome, 7 had isolated CHF, 1 had ARPKD, and 1 had Type V choledochal cysts. Youngest patient with cholangiocarcinoma was 33 years, all other cases involved patients >40 years.

Transplantation: Isolated kidney 91 (95% in ARPKD), Isolated liver 173 (87% had Caroli), Combined 23.  Three renal patients subsequently had combined transplantation.

Other important points:

  • CHF is not ‘typically associated with progressive hepatic insufficiency.’ Only rarely is hepatic synthetic function compromised
  • Predisposition to cholangitis may affect transplantation decisions and timing

Outcomes of Biliary Atresia

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