NASPGHAN Postgraduate Course 2017 (Part 3): Biliary Atresia, NAFLD, SMOFlipid, Pancreatic Pain

This blog entry has abbreviated/summarized these presentations. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

Here is a link to postgraduate course syllabus: NASPGHAN PG Syllabus – 2017

Biliary Atresia: Update on diagnostic and prognostic biomarkers and therapeutic interventions

Cara Mack    Children’s Hospital of Colorado

Key points:

  • 84% of biliary atresia is isolated; 16% are syndromic with other defects
  • Direct bilirubin is (mildly) elevated at birth in patients with biliary atresia
  • Total bilirubin 3 months after Kasai predicts outcome. If <2 mg/dL, then unlikely to need a transplant in the first 2 years of life.
  • Reviewed biomarkers including Th1, Autotaxin, IL-8

Therapeutic interventions:

  • Nutritional support. Better nutrition improves outcomes after liver transplantation.
  • Fat soluble vitamin supplementation
  • Cholangitis prevention. Some studies have shown that prophylactic antibiotics may reduce incidence of cholangitis.
  • No therapeutic interventions that delay progression of this disease



CHILDREN Cohort Mgt of Vitamin Supplementation

Steroids are not helpful after Kasai procedure

Diagnosis and Management of Pediatric NAFLD 2017

Stavra Xanthokos   Cincinnati Children’s Hospital Medical Center

Key points:

  • NAFLD is #2 cause of liver transplantation in adults and on its way to becoming #1
  • ALT is still the best screening tool; NASPGHAN guidelines recommends screening overweight/obese children 9-11 years of age
  • Ultrasound has poor sensitivity and specificity for NAFLD; it is helpful for detecting gallbladder disease
  • Bariatric surgery has been effective for NAFLD


SMOFlipid and the Pediatric Patient

Peter Wales  Hospital for Sick Children (Toronto)

Slides are not available in syllabus

Key points:

  • Improving outcomes noted in the intestinal failure population
  • Dr. Wales reviewed proposed improvements with Omega-3 lipids -less cholestasis, less hepatitis, and less fibrosis
  • Compared improvements with lipid minimization (1 g/kg/day) compared to newer agents: omegaven and SMOFlipid. Additional studies are needed due to limitations of previous studies
  • Discussed SMOFlipid vs. Intralipid trial at 5 centers in Canada. N=24.
  • At SickKids: SMOFlipid for all preterms at admission & for term infants after 2 weeks of PN. Dosing 2-2.5 g/kg & now accounts for 85% of lipid usage at institution
  • None of the lipid products were designed for preterm infants. Intralipid has a pediatric indication and other products are used off label
  • Lipid restriction probably affects brain size/development; thus, a lipid agent that allows for higher doses likely will be beneficial for developmental outcomes.  The retina can be used as a biomarker of the brain affects of lipids.

Painful Chronic Pancreatitis: Management/therapeutic interventions

Vikesh Singh  Johns Hopkins University School of Medicine

Slides are not available in syllabus




FDA Warning on Eluxadoline (Viberzi)

Briefly noted: The FDA has issued a safety warning for patients with irritable bowel syndrome who have had their gallbladder removed.

FDA Warns of Increased Risk of Serious Pancreatitis with irritable bowel drug eluxadoline (Viberzi) in patients without a gallbladder

An excerpt:

Viberzi is a prescription medicine used to treat irritable bowel syndrome in adults when the main symptom is diarrhea (IBS-D)…From May 2015, when Viberzi was first approved, through February 2017, FDA received 120 reports of serious cases of pancreatitis or death.* Among the 68 patients who reported their gallbladder status, 56 of them did not have a gallbladder and received the currently recommended dosage of Viberzi. Seventy-six patients were hospitalized, of which two patients died.

My take: Now that this warning has been issued, there may be additional cases identified. While this medication is mainly used in adults, pediatric gastroenterologists need to be aware of this risk in counseling potential patients.

Related blog posts:

Palace of Versailles -fountain turned off!


Top Posts 2016

The following posts are the ones that I think are most useful from 2016.








Complex Family of CFTR-Associated Disorders

While most clinicians are familiar with cystic fibrosis (CF), much fewer are familiar with a group of disorders related to the cystic fibrosis transmembrane conductance regulator (CFTR) that do not meet the criteria for cystic fibrosis.  A summary of these disorders is provided in a recent editorial (Levy H, Farrell PM. J Pediatrics 2015; 166: 1337-40).  In addition, the editorial provides insight into a related study: Groves T et al.. J Pediatrics 2015; 166: 1469-74.

The editorialists note that new disorders have been created due to newborn screening and due to the use of CF mutation analysis.  New disorders:

  • CRMS -CFTR-related metabolic syndrome.  CRMS describes infants with elevated immunoreactive trypsinogen and inconclusive sweat testing and DNA results.  Inconclusive sweat testing includes sweat tests 30-59 mmol/L if age <6 months or 40-59 mmol/L if >6 months on at least 2 occasions.  DNA testing is inconclusive if there are fewer than 2 CF disease-related mutations identified.  DNA testing is also considered inconclusive if there are 2 CFTR mutations but sweat testing is normal.
  • CFTR-RD -CFTR related disease.  CFTR-RD describes symptomatic individuals beyond infancy who have sweat testing <60 mmol/L and up to 2 CFTR mutations, at least one of which is not clearly categorized as a CF-causing mutation.  Thus, these individuals do not fulfill criteria for CF but could have congenital bilateral absence of vas deferens, acute recurrent or chronic pancreatitis, or disseminated bronchiectasis.
  • Delayed CF -Delayed CF describes patients eventually diagnosed with CF who had initially intermediate sweat chloride values.  Over time, their condition evolves to fulfill the criteria for CF.  In the retrospective study by Groves et al, 14 of 29 (48%) evolved to a diagnosis of CF.  These patients with delayed CF had less pancreatic insufficiency (OR 0.06), milder obstructive lung disease, less colonization with Pseudomonas aeruginosa (OR 0.04), and overall disease severity as measured by Shwachman scores at 2 years.
  • Nutritional outcomes were improved at 2 years in this Delayed CF cohort in comparison to 28 matched patients diagnosed with CF in the newborn period, but did not persist to later ages.

The editorial notes that nearly 20% of patients with CF are being enrolled in the CF foundation patient registry without sweat chloride testing results.  They do not favor this approach because the diagnosis of CF requires proof of CFTR dysfunction, not simply CF DNA mutations.

Take-home message: Patients who do not meet the criteria for CF  but who have intermediate sweat testing or abnormal CF DNA mutations need to be followed.  Some will fulfill the criteria with time and others may develop other clinical problems even without having CF.

Why an ERCP Study Matters to Pediatric Care

While there are pediatric patients who undergo endoscopic retrograde cholangiopancreatography (ERCP), this is a relatively infrequent occurrence. Nevertheless, a recent study has a couple useful clinical pearls that may have broader application.

  1. Clin Gastroenterol Hepatol 2014; 12: 303-07.
  2. Clin Gastroenterol Hepatol 2014; 12: 308-10 Associated editorial
  3. Gastroenterol 2014; 146: 581-82. Associated summary

Key points/Implications:

  • Aggressive hydration may prevent post-ERCP pancreatitis. In the study, the treatment group received an average of 3290 mL over the 9-hour period compared with 945 mL in the standard infusion group.
  • Implication: The speculation from the study and the editorials is that improved pancreatic perfusion will result in better oxygenation and reduce the likelihood of  pancreatitis. In the 2nd reference, the author states that his practice is to administer “at least 3 L of crystalloid in recovery to young, healthy patients who have undergone high-risk ERCP and an additional 3 to 5 L within the first 12 hospital hours to those admitted with postprocedure pain”
  • The best fluid (for post-ERCP and acute pancreatitis) may be lactated Ringer’s (LR).
  • Implication: The lactate in LR may help reduce pancreatitis by avoiding acidosis which could promote zymogen activation and pancreatic inflammation. A previous small trial (n=40) of acute pancreatitits from any cause showed lesser degrees of systemic inflammatory response with LR in compared with normal saline (Clin Gastroenterol Hepatol 2011; 9: 710-17e1).
  • This study adds aggressive IVFs as another intervention to prevent ERCP.  Rectal indomethacin and prophylactic stent placement (in high-risk patients) are other accepted treatments.

Study details:

This pilot study randomly assigned 39 patients to aggressive hydration and 23 to standard hydration; all patients were inpatients who were not at risk for fluid overload. The aggressive group received 3 mL/kg/h during the procedure, a 20 mL/kg bolus after the procedure, and then continued on 3 mL/kg/hr for 8 hours.  In contrast, the standard group received LR at 1.5 mL/kg/h during and for 8 hours afterwards.

Demographics: The average age was 43 years in the aggressive hydration group and 45 years in the standard group. 78% were hispanic.  The ERCP procedures were mostly “average risk.”  74% had ERCP for choledocholithiasis.  Only 2 subjects needed precut sphinterotomy (3%).


  • No patients in the aggressive hydration group developed acute pancreatitis compared with 4 (17%) in the standard hydration group
  • Elevated amylase (23% vs. 39%) and epigastric pain (8% vs 22%) were also less frequent in the aggressive hydration group.

Numerous Limitations: This was a small pilot study with an atypical population; thus, the findings are difficult to generalize.  A false-positive (type 1 error) can easily occur due to the small numbers, especially as the standard hydration group had a rate of acute pancreatitis that was about double from previous studies. In addition, this study was not blinded and could have been susceptible to bias.  Furthermore, the authors defined acute pancreatitis differently than in previous studies.  In this study, the authors required enzyme increases 2 or 8 hours after ERCP with new abdominal pain; in previous studies, the definition of acute pancreatitis relied on enzyme increases for at least 24 hours after the ERCP.

Take-home message for those not doing ERCPs: Think about using lactated ringer’s and aggressive hydration in otherwise-well patients who present with acute pancreatitis.

Related blog entries:

For the pediatric pancreatologists

Pancreatitis is a terrible affliction whether acute, recurrent or chronic.  While pediatric patients often have “mild” problems from acute pancreatitis, even in these cases the pain is usually severe and the treatment, which consists mainly of holding feedings and providing pain relief, does not impress anyone.

A few recent references do provide more data on several aspects of pancreatitis.

The first reference, J Pediatr 2013; 162: 788-92, provides data on the rare problem of acute necrotizing pancreatitis in children.  This retrospective study encompassing 21 years identified seven children.  CT scan showed necrosis of more than 30% and/or more than a 3 cm area in all of these patients.  Etiologies included medications (L-asparaginase, Valproate, Minocycline), diabetes (n=1), and gallstones (n=1).  No patients needed surgery or died.  After discharge, 5 patients had complications which included pseudocysts, diabetes, and pancreatic exocrine insufficiency.

Key points:

  • CT scan (with contrast) is useful in diagnosis and assessment of severity.
  • Initial presentation is similar to cases of acute pancreatitis without necrosis.  Long-term complications are increased.

The second reference: Gastroenterol 2013; 144; issue 6.  The entire issue is devoted to pancreas issues.  Pages 1272-81 review acute pancreatitis, pages 1282-91 review chronic pancreatitis, and pages 1292-1302 review genetic risk factors.

Page 1288 provides a suggested management algorithm for chronic pancreatitis:

Medical therapy recommendations include alcohol/smoking cessation, counsel regarding nutrition/vitamin D/calcium, consider analgesics (start with tramadol), consider adjuncts for pain (e.g.. neuron tin, SSRI, SSNRI, TCAs), assess exocrine and endocrine function (elastase and HgbA1C), use steroids if autoimmune pancreatitis.

If medical therapy ineffective, assessment of pancreatic duct is recommended.  Based on this information, discussion of endoscopic and surgical treatment is outlined as well.

Related blog entries:

INSPPIRE for pancreatitis

While anyone who follows this blog knows that I like acronyms, I must say that many investigators have taken lessons from Krispy Kreme on spelling.  INSPPIRE is named for the International Study Group of Pediatric Pancreatitis: In Search for a Cure.  A study from this group reports on definitions of pediatric pancreatitis & surveys current practice (JPGN 2012; 55: 261-65).

The literature regarding acute recurrent pancreatitis and chronic pancreatitis in children is limited.  This consortium hopes to change this.  As a start, the authors assigned subcommittees to establish definitions, reviewed the literature, and assessed current practice.


  • Acute pancreatitis (AP): requires at least 2 of 3 criteria:
  1. Abdominal pain consistent with AP
  2. Serum amylase and/or lipase activity at least 3 times ULN
  3. Imaging findings compatible with AP
  • Acute recurrent pancreatitis (ARP): requires at least two episodes of AP along with

Complete resolution of pain (≥ 1-month pain-free interval) OR complete normalization of pancreatic enzyme levels along with resolution of pain (can be shorter interval than 1 month)

  • Chronic pancreatitis (CP): requires one of the following:
  1. Abdominal pain and imaging suggestive of chronic pancreatic damage
  2. Exocrine pancreatic insufficiency and imaging suggestive of chronic pancreatic damage
  3. Endocrine  pancreatic insufficiency and imaging suggestive of chronic pancreatic damage
  4. Surgical/histologic specimen consistent with chronic pancreatitis

Managing pancreatitis:

Typical tests for these three conditions are shown in figure 2 and vary widely.  For AP, most respondents (63%) routinely checked liver enzymes, triglycerides, calcium and abdominal ultrasound.  For ARP and CP, most respondents (69%) obtained additional imaging modalities (eg. MRCP), genetic testing, and sweat chloride. If ERCP was needed, 88% of practices relied on adult gastroenterology colleagues.

Related blog posts:

Recurrent pancreatitis and genetic underpinnings | gutsandgrowth

Does pancreas divisum cause pancreatitis? | gutsandgrowth

How helpful are antioxidants for chronic pancreatitis pain