Category Archives: Uncategorized

Primary Sclerosing Cholangitis (PSC) –Natural History Study

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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)

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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

Better Hydration May Lead to Better Outcomes For Hemolytic Uremic Syndrome due to E coli

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According to a recent meta-analysis of 8 studies (1511 children), better hydration may reduce the risk of bad outcomes for hemolytic uremic syndrome (HUS): From JAMA Pediatrics: Shiga Toxin-Producing E coli, Hydration Status and Outcomes of Patients Infected With Shiga Toxin–Producing Escherichia coliA Systematic Review and Meta-analysis

Reference: JAMA Pediatr. Published online November 28, 2016. doi:10.1001/jamapediatrics.2016.2952

Results: A hematocrit value greater than 23% as a measure of hydration status at presentation with HUS was associated with the development of oligoanuric HUS (OR, 2.38 [95% CI, 1.30-4.35]; I2 = 2%), renal replacement therapy (OR, 1.90 [95% CI, 1.25-2.90]; I2 = 17%), and death (OR, 5.13 [95% CI, 1.50-17.57]; I2 = 55%). Compared with putatively hydrated patients, clinically dehydrated patients had an OR of death of 3.71 (95% CI, 1.25-11.03; I2 = 0%). Intravenous fluid administration up to the day of HUS diagnosis was associated with a decreased risk of renal replacement therapy (OR, 0.26 [95% CI, 0.11-0.60]).

Conclusion from abstract: Two predictors of poor outcomes for STEC-infected children were identified: (1) the lack of intravenous fluid administration prior to establishment of HUS and (2) a higher hematocrit value at presentation. These findings point to an association between dehydration and adverse outcomes for children with HUS.

This study is in agreement with a prior study referenced on this blog: Changing Paradigm in Hemolytic Uremic Syndrome

acadia5

 

Improved Understanding 18 Years Later

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A deeply painful experience for me occurred 18 years ago when a child that I cared for had a complication following an endoscopy.  Now, a recent publication (A Sierra et al. JPGN 2016; 63: 627-32) provides relevant information.  To be clear, this article would not have averted the complication but may help explain why it happened.

This retrospective study from 2010-2014 identified 7 cases of biopsy-induced intraduodenal hematoma (IDH) from a total of 2705 nontherapeutic upper endoscopies and 1163 duodenal biopsies.

Key findings:

  • 6 of 7 children had undergone a bone marrow transplantation and were at risk for graft-versus-host disease (GVHD)
  • 1 had Noonan syndrome
  • Thrombocytopenia was NOT correlated with IDH
  • No early perforations were associated with IDH

As part of this study, the authors reviewed the entirety of published IDH in children, 47 cases.  One prior author, Sahn et al (JPGN 2015; 60: 69-74) suggested that any organ transplant could increase the risk of IDH.  In this series, 29% of their patients had undergone transplantation (2 liver, 1 heart, 1 BMT).  Interestingly, among the entire 47 cases, there had been another report of a child with Noonan syndrome, suggesting some underlying susceptibility in the coagulation or platelet function pathways.

Clinical features of IDH:

  • Following endoscopy, particularly the first 3 days, signs/symptoms included epigastric pain, abdominal tenderness, and vomiting
  • Imaging including U/S, CT and MRI can confirm diagnosis
  • Resolution can take 2-3 weeks, during which parenteral nutrition is needed
  • IDH can cause acute pancreatitis or obstructive cholestasis
  • In trauma-induced IDH, surgery is much more likely than with endoscopic/biopsy-induced IDH

My take: BMT (and other types of transplantation) markedly increase the risk of biospy-induced duodenal hematoma. In this series, 7% of BMT patients had IDH compared with 0.1% of all others.

Related blog posts:

Jones Bridge & Chattahoochee River

Jones Bridge & Chattahoochee River

Liver Briefs 2017

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Briefly noted:

RJ Fontana et al. Hepatology 2016; 64: 1870-80.  In this study of 681 adults with acute liver failure in U.S., only 3 had detectable anti-HEV IgM and all three were negative for HEV-RNA.  In addition, other putative causes of acute liver failure were present in all three.  My take: Hepatitis E is very rare explanation for acute liver failure in the U.S.

RA Rosencrantz et al. Hepatology 2016; 64: 2253-6. Case report of 2.5 yr old with autoimmune sclerosing cholangitis with Kawasaki disease. This was a well-described case with MRCP and liver histology. My take: In patients with Kawasaki with protracted liver disease, another etiology to consider.

Related blog posts:

St Maarten

St Maarten

Top Posts 2016

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

Gastroenterology:

Liver:

General:

Doctoring:

IBD:

Nutrition:

truth-johnpohl

Bad Combination? Lansoprazole and Ceftriaxone

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From Gastroenterology & Endoscopy News Nov 2016: Giving PPIs and Antibiotics Together May Disrupt Heart Rhythm

An excerpt:

Taking two common drugs—an over-the-counter proton pump inhibitor (PPI) and an antibiotic—together was associated with an increased risk for life-threatening arrhythmia (J Am Coll Cardiol 2016 Oct 10. [Epub ahead of print]).

New York researchers scanned data from two independent databases to investigate possible QT interval–prolonging drug–drug interactions: 1.8 million adverse event reports from the FDA’s Adverse Event Reporting System and 1.6 million ECGs from 382,221 patients treated at NewYork-Presbyterian Hospital/Columbia University Medical Center, in New York City, between 1996 and 2014…

In the study, patients taking ceftriaxone, a cephalosporin antibiotic, and the PPI lansoprazole were 40% more likely to have a QT interval above 500 milliseconds, the current FDA-stated threshold of clinical concern. Among men taking the two drugs, QT intervals were 12 milliseconds longer than men who took either drug alone…

The interaction identified in the data analysis was specific to lansoprazole and ceftriaxone, but not other cephalosporins.

My take: The magnitude of this risk is very low for a single individual but is important when one considers how many patients could be taking this combination of medications.

Easily Overlooked Esophageal Inlet Patch

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Background: In numerous articles, it is stated that an esophageal inlet patch (IP) is often missed during routine endoscopy.  IP, a salmon-colored, velvet-appearing, distinct area of heterotopic gastric mucosa, typically is located just distal to the upper esophageal sphincter and is usually a single lesion ranging from a few millimeters to >5 cm.  Estimates on prevalence ranges from 0.1% to 10%.

A recent study (G Di Nardo et al. J Pediatr 2016; 176: 99-104) examined 1000 consecutive patients <18 years. Symptoms often attributed to IP include chronic cough, sore throat, dysphagia, globus pharyngeus, hoarseness, and vocal cord dysfunction.

Key findings:

  • The authors noted an IP incidence of 6.3%.
  • 35 of the 63 patients were asymptomatic.
  • The authors state that 17 of the 63 patients had chronic IP-related symptoms and all 17 were unresponsive to PPI therapy.  All were treated “successfully” with argon plasma coagulation (APC)
  • Median size was 13.3 mm.
  • The authors state that they did not find any acid-independent episodes related to IP, though pH-MII studies did help identify several patients with underlying GERD.

My take: Since the treatment of IP was not randomized/blinded and many patient’s with IP are asymptomatic, it remains unclear to me how many patients with IP truly benefit from APC treatment.

acadiaharbo

Yoga Therapy for Abdominal Pain

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A recent study (JJ Korterink et al. JPGN 2016; 63: 481-7) showed that yoga treatment may be helpful with children (8-18 years) with functional abdominal pain.  The authors studied 69 subjects who received either standard medical care or standard care with yoga therapy.  Pain intensity was followed with a pain dairy as was quality of life with KIDSCREEN-27. Key finding: At 1 year follow-up, 58% of the yoga group had a treatment response compared to 29% in the control group.  Yoga therapy was associated with reduction in school absences as well as reduced abdominal pain.

While yoga is considered helpful in stress management and has been suggested as treatment for adults with irritable bowel, an associated editorial by Yvan Vanderplas (pg 451) notes that the scientific basis for yoga therapy remains weak. He notes that yoga trials are biased due to selection bias and the results are tainted due to lack of blinding with regard to the intervention.

My take: If families are interested in yoga therapy, this should be encouraged.  Yoga therapy is safer and at least as effective as many other therapies offered for abdominal pain.

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Ursodeoxycholic Acid, Cystic Fibrosis, and the Problem with Surrogate Markers

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A recent study (C Colombo et al. J Pediatr 2016; 177: 59-65) examined 20 patients with cystic fibrosis-associated liver disease (CFLD) who were receiving ursodeoxycholic acid (UDCA) for at least 2 years.  Specifically, they wanted to focus on the extent of biotransformation of UDCA to its hepatotoxic metabolite, lithocholic acid.  The possibility that long-term UDCA therapy could be detrimental was propelled by a primary sclerosing cholangitis study (K Lindor et al. Hepatology 2009; 50: 808) which indicated that high doses of UDCA resulted in worse outcomes despite better “liver function tests.”

Dosing of UDCA: 20 mg/kg/day

Key findings: UDCA became the predominant serum bile acid; 2 hours after UDCA administration, “both UDA and chenodeoxycholic acid significantly increase (P< .01), but no significant changes in serum lithocholic acid concentrations were observed.”

What does this study prove?

Well, not very much.  There are other potential mechanisms for UDCA toxicity and as the editorial notes, “we still lack the necessary endpoints in CF liver disease with which to assess the efficacy of UDCA or any therapy that is on the horizon.”

My take: Because our surrogate markers are unreliable for CFLD, there really is no way to know with certainty whether UDCA therapy is beneficial.

gardenpic3