#NASPGHAN17 Presentations at Annual Meeting: GGT in PSC, Nutrition for Intestinal Failure

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

Improvement in GGT Predicts Event-free Survival in Primary Sclerosing Cholangitis Regardless of Ursodeoxycholic Acic Treatment. 

Mark Deneau et al. (Grand Watkins Prize).

Key points:

  • PSC is difficult to study due to its rarity and due to its slow progression; thus surrogate biomarkers are needed.
  • Alkaline phosphatase is not a good biomarker in children
  • GGT level at one year after diagnosis was predictive of prognosis
  • Ursodeoxycholic acid does not appear to be effective

Optimizing Nutrition in Intestinal Failure

Justine Turner, University of Alberta

Key points:

  • Human milk is an ideal “formula” for infants, including those with intestinal failure
  • Oral feedings are important
  • Combination of bolus feeds and continuous feeds is reasonable
  • SMOFlipid allows higher lipid dose administration without hepatoxicity; this may improve cognitive outcomes
  • Amino acid based formulas have higher osmolality which can contribute to diarrhea

Patients with >50% of small bowel and >50% of colon were most likely to achieve enteral autonomy (GIFT registry)



#NASPGHAN17 Annual Meeting Notes (Part 1): Neurostimulation for RAP, PSC-IBD, Organoids

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.

William Balistreri Prize: Katja Kovaic et al. Neurostimulation for functional abdominal pain disorders in children –a randomized, double-blind, sham-controlled trial. This study enrolled 104 patients.  Lancet Gastroenterol Hepatol 2017; 2: 727-37.

Summary slide:

Fellow Research Award: Symptoms Underestimate Endoscopic Activity in PSC-IBD. Amanda Ricciuto et al. Hospital for Sick Children.

Key points:

  • In patients with IBD-PSC, clinical remission based on clinical symptoms is not reliable indicator of histologic remission.
  • Patients with PSC-IBD are more likely to have active endoscopic disease even when in “clinical remission”
  • Calprotectin levels (not PUCAIs) are helpful in confirming clinical remission.  A calprotectin <93 mcg/g was optimal level in determining clinical remission
  • Better control of disease could improve clinical outcomes (eg. colon cancer, liver progression)

Keynote Address: Organoids: Current and future promise for changing treatment of gastrointestinal and liver disorders.  James Wells Cincinnati Children’s Hospital Medical Center.

This was a terrific lecture.

  • Example of use of pluripotent stem cell usage: Diabetes. Phase 1 study has been started.
  • Organoids are in essence miniature versions of organs in a dish and with complex combination of cell types.
  • Organoids allow easier testing on these tissues for treatment and diagnosis of diseases
  • Organoids will allow for personalized testing of medications.  Some patients will respond differently.  This technology could be used to grow a specific organoid for a specific person and determine response on the organoid before giving to the patient.
  • Can engraft organoids into mice which can provide blood supply and allow larger organoids.
  • Clinical projects for organoids: Hirschsprung’s,  H pylori, Clostridium difficile, Short bowel syndrome, Fatty liver disease

Big Study of Primary Sclerosing Cholangitis -Pediatrics 2017

In July, this blog reviewed a recent big study of primary sclerosing cholangitis (PSC) in adults with more than 7000 patients. A recent study in the pediatric age group enrolled 781 children from 36 institutions: MR Deneau et al. Hepatology 2017; 66: 518-27 (Congratulations to Nitika Gupta and Miriam Vos -in-town colleagues and contributing authors to this study.)

This retrospective study’s key findings:

  • Median age 12 years at diagnosis; 39% were female
  • Autoimmune hepatitis (overlap) was present in 33%
  • Small-duct PSC was present in 13%
  • Inflammatory bowel disease (IBD) was present in 76%
  • PSC-IBD and Small-duct PSC (normal cholangiograms) had more favorable prognosis with hazard ratio of 0.6 of developing complications
  • Portal hypertensive and biliary complications were noted in 38% and 25% respectively. After developing these complications, the median survival with native liver was 2.8 years and 3.5 years respectively
  • Survival with native liver was noted in 70% at 5 years and 53% at 10 years
  • Elevations in bilirubin, GGT, and AST-to-platelet count ratio were associated with highest risk of progressive disease.
  • Cholangiocarcinoma (CCA) developed in 1% (median, 6 years after diagnosis)

The discussion notes that while pediatric PSC is a progressive disease, complications were slower to develop compared with adult-onset PSC. 10-year survival with native liver is typically lower in adults ~60% (vs 70% in this study).  “Up to one third of adults with PSC may have esophageal varices within a year of diagnosis” compared with only 13% in this cohort.  Dominant strictures are more common in adults, occurring in the majority within 5 years whereas this occurred in 16% of this cohort.

With regard to CCA, the authors note that current recommendations suggest starting to screen for CCA in patients over age 18 years with ultrasound and CA 19-9 at 6-12 month intervals. These studies “could reasonably be extended to PSC patients aged 15 and above and [for those requiring dilatation] of biliary strictures.”

My take: This large pediatric PSC study provides more clarity on the outcomes of patient’s with PSC and the associated conditions.

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Big Study of Primary Sclerosing Cholangitis

This blog has reviewed multiple publications on primary sclerosing cholangitis (see blog posts below). Now, a study from 37 centers with 7121 patients with PSC has been published: TJ Weismuller et al. Gastroenterol 2017; 152: 1975-84. Given the relative infrequency of PSC, this retrospective report offers more insight into the predictors of the clinical course of PSC.

Key points:

  • Most of the patients in the study had large duct PSC (89.8%); 3.6% had small duct disease and 6.6% had overlapping PSC/autoimmune hepatitis.
  • Mean age of cohort at diagnosis was 38.5 yrs.
  • 70% of PSC patients developed IBD with ulcerative colitis (UC) about 5-times more common than Crohn’s disease.
  • 37% of patients met the primary endpoint of either liver transplantation or death
  • Individuals with small duct PSC had a favorable outcome; only one of 254 (0.4%) developed cholangiocarcinoma (CCA). Risk of primary endpoint was much lower in small duct PSC compared with classical PSC with an adjusted hazard ratio of 0.23.
  • Individuals with PSC/AIH variant also had a reduced risk of primary endpoint compared with classical PSC with an adjusted hazard ratio of 0.73.
  • Overall, CCA occurred in 594 patients (8.3%); the incidence of CCA changed markedly with the age of the patient.  In the youngest group (<20 years), the rate was 1.2 per 100 patient-years, it was 6.0 in 21-30 yr-olds, 9.0 for 31-40 yr-olds, 14.0 fr 41-50 year olds, 15.2 for 51-60 yr-olds, and 21.0 per 100 patient-years in those older than 60 years.
  • The absence of IBD, particularly UC, was associated with a lower risk PSC clinical course. Patients with UC had increased liver disease progression compared with patient’s with Crohn’s disease, with a HR of 1.56.
  • The median transplant-free survival time was 14.5 years; the estimated survival was approximately 21 years in the entire cohort

It is noted that an important limitation is that the cohort is from specialist centers and may not reflect a more typical population-based cohort; that is, this patient population is likely to be severely affected.

My take: Patients with small-duct PSC have a much lower risk of disease progression.

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Piedmont Park Arts Festival

Liver Problems with Inflammatory Bowel Disease

A recent review (Full text: LJ Saubermann et al. JPGN 2017; 64: 639-52)  discusses the hepatic issues and complications associated with inflammatory bowel disease.

Key topics:

  • Primary Sclerosing Cholangitis (PSC)
  • Autoimmune Hepatitis (AIH)
  • Autoimmune Sclerosing Cholangitis (ASC)
  • Portal Venous Thrombosis/hypercoagulability
  • Cholelithiasis (more common in Crohn’s disease if diseased terminal ileum)
  • Viral hepatitis
  • Drug-Induced Liver Disease
  • Fatty Liver disease

Many of these topics have been discussed previously on this blog.  A couple of pointers in this review:


  • Greater risk of colorectal carcinoma
  • IBD-PSC patients are at higher risk for pouchitis
  • GGT of >252 U/L “was highly sensitive (99%) and had good specificity (71%) for PSC” [or ASC]
  • The authors recommend “screening all newly diagnosed patients with IBD with ALT and GGT
  • Immunosuppressive therapy is NOT effective
  • Vancomycin therapy is currently being tested (clinical trials: NCT02137668 & NCT01802073)


  • Less frequent in IBD patients than PSC
  • Most common treatment is prednisone/azathioprine
  • 40-80% of children have cirrhosis at AIH diagnosis, but “progression to end-stage liver disease is rare and …with appropriate treatment, 80% of patients achieve remission.”


  • ASC is an overlap syndrome between AIH and PSC
  • “It is important that children with IBD and apparent AIH are routinely investigated for evidence of biliary disease with MRCP”
  • “ASC responds to the same immunosuppressive combination therapy used for AIH”

HAV/HBV Immunization:

  • HAV vaccination is effective in patients with IBD…although the rate [seroconversion] was significantly lower” in patients receiving anti-TNF therapy (92.4% vs 99.1% in one study).
  • In those needing HBV immunization: “One strategy evaluated to improve HBV immunity in adults with IBD is an accelerated course with double vaccine doses at 0, 1, and 2 months.”

Methotrexate (MTX):

  • “The extent of histological features of hepatotoxicity secondary to long-term MTX use in IBD has been infrequently described; however, the inicdence of significant abnormal histological findings appears to be rather low.”

My take: This article is a good starting point for liver-related issues in IBD.  For concerns regarding medications, the NIH livertox website is more useful and much more comprehensive.

Related blog entries:






Primary Sclerosing Cholangitis (PSC) –Natural History Study

Last week, I posted an blog referencing new guidelines for peanut introduction.  A more detailed explanation of these guidelines: New Guidelines: Early Introduction of Peanut to Prevent Peanut Allergy from David Stukus (Thanks to Kipp Ellsworth for sharing this information)


A recent study (PL Valentino et al. JPGN 2016; 63: 603-09) follows “the largest reported pediatric PSC cohort” to determine the natural history.

Study characteristics:

This retrospective study followed 120 children (1-21 yrs) with a median age of 14 years.  27% had autoimmune sclerosing cholangitis (ASC), 63% had PSC; 24% (n=29) of entire cohort had exclusive small duct PSC. Median followup was 3.7 years.

Key findings:

  • 81% of PSC patients had inflammatory bowel disease; most (72/97) had ulcerative/indeterminant coliits. 40/72 had pancolitis.
  • PSC-IBD was more common than ASC-IBD (85% vs 68%).
  • 10-year transplant-free survival in this cohort was 89%; there were 6 liver transplants.
  • The rate of cirrhosis was lower in the group who had IBD preceding PSC (15% vs 31%,P=0.05).
  • PSC is clinically silent in the majority of patients; 64% presented with abnormal chemistries and no other symptoms.
  • ERCP therapeutic intervention was low, 3% for stenting and 7% for balloon dilatation.

The authors speculate that one reason for milder PSC-IBD disease could relate to the fact that IBD patients undergo frequent chemistries.  In those without IBD, subacute PSC could be present for a much longer period before detection.  The authors note that PSC in children presents as a milder disease with only 10% having cirrhossi compared with 30% in studies with adult patients.

My take: We have a lot to learn about PSC including which patients are likely to develop clinically significant liver disease and whether most patients benefit from treatment.

Related blog post: Should we care about subclinical PSC? (This post has links to others related to PSC)

Thunder Hole, Acadia Nat'l Park

Thunder Hole, Acadia Nat’l Park

Should We Care About Subclinical Primary Sclerosing Cholangitis with Inflammatory Bowel Disease?

A recent study (AK Lunder et al. Gastroenterol 2016; 151: 660-69, editorial 590-3) provides more information about the prevalence of subclinical primary sclerosing cholangitis (PSC) in the setting of long-term inflammatory bowel disease. From a cohort of 756 Norwegian patients in the “IBSEN” cohort of patients with inflammatory bowel disease, the authors analyzed 327 patients with magnetic resonance cholangiography (MRC).

Key findings:

  • 24 (7.5%) of 327 patients who had been followed for 20 years were found to have PSC lesions.  Only 7 (2.2%) were known to have PSC based on biochemical or clinical features. Subsequently, a missed case of small-duct PSC was recognized increasing the rate to 8.1%.
  • Subclinical PSC, interestingly, was detected more often in Crohn’s patients (9.0%) compared with ulcerative colitis (6.8%)
  • Extensive colitis, high prevalence of colectomy, and refractory IBD symptoms were more common in patients with suspected PSC compared with those without PSC features (P= .029, P= .002, and P= .012 respectively)

The natural history of these subclinical cases of PSC is unclear.  Studies have shown that patients with PSC with normal alkaline phosphatase values have an excellent outlook.  Yet, there should be some concern.  PSC has been associated with 400-fold higher chance of cholangiocarcinoma and 5-fold increased risk of developing colorectal cancer.  This could indicate the need for more intensive surveillance in these patients –though the exact risks in those with subclinical disease is unknown.

My take: Until we know more, I doubt looking for subclinical PSC makes sense outside research protocols.

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