Moving to MRE

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A recent review (JPGN 2014; 59: 429-39) regarding imaging for inflammatory bowel disease reiterates the accepted view that magnetic resonance enterography (MRE) is typically the most useful imaging test for children with inflammatory bowel disease; in Table 5, MRE is listed for each indication, though CT scan is recommended “if emergent or after hours.”  The review reviews prior pediatric publications, radiation risks (with non-MRE studies), and alternative imaging.  The discussion on costs is minimized, though the authors note that MRE is the most expensive and can be compromised by motion artifact. As a practical matter, I think giving a typical charge (or range) for each of the imaging techniques would be helpful.  Also, another important issue is assuring that radiologists have the technical expertise to obtain quality imaging.

Another study (Clin Gastroenterol Hepatol 2014; 12: 1702-07) retrospectively looked at 1095 emergency room visits by 613 individuals (average age ~40 years) to determine if they could develop a model to limit unnecessary CT scans.  Of the 1095 CT scans, 24.8% were normal; 10.9% had either perforation or non-perianal abscess.  In their discussion, they note that the equation “no scan for ESR (mm/h) + 5*CRP (mg/dL) ≤10” would avoid 18.5% of CT scans.  Implementation of a more complex model could eliminate up to 43% of the CT scans.  The algorithm (Figure 2) suggested by the authors:

  • Assess for obstruction.  If suggestive symptoms, obtain abdominal X-rays.  If concerns for obstruction remain, consider CT scan.
  • If not concerned about obstruction, is there a high likelihood of perforation or abscess? If yes proceed with CT scan.  If not, consider anti-inflammatory therapy if CD symptoms present (without imaging).

Here’s the link to the abstract –supplementary materials can be obtained by those who log in.   http://dx.doi.org/10.1016/j.cgh.2014.02.036

Bottomline: Cross-sectional imaging is particularly helpful at determining whether complications are developing in patients with inflammatory bowel disease.  Increasing use of MRE will reduce radiation risks.

With regard to costs, a recent NPR story discussed “How Much Is That MRI, Really? Massachusetts Shines A Light.” While this story discussed costs related to a Massachusetts law which mandates that insurers reveal the costs of various tests, it did not relate any information regarding quality.  The study implied that an MRI at one institution would be equivalent to an MRI at another.  This is not the case.

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Sorting Out Discrepancies in Hepatitis B Testing

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A recent study (J Pediatrics 2014; 165: 773-8) highlighted the clinical problem of discrepant hepatitis B virus (HBV) testing in pregnant women.

Design: The Centers for Disease Control and Prevention analyzed a nonrandom sample of discordant cases of HBV reported by US Perinatal Hepatitis B Prevention Program.  Discordant cases indicated that there were differences between an initial HBsAg result and a subsequent test.  Among 142 cases, 89 had sufficient information to determine accuracy of the initial test.

Key finding: 14 (15.7%) of these cases were true positives, the remainders were false-positives.

How did authors sort out cases?

Negative testing for “total anti-HBc or no detectable HBV DNA result indicating no HBV infection…A positive total anti-HBc indicates current or past HBV infection, is not elicited by vaccination, and usually persists for life.”

Pointers regarding serology:

  • IgM anti-HBc -acute or recent infection and can persist for more than 6 months.
  • HBV DNA confirms active infection and can detect infection at levels below those of HBsAg assays.  This can occur either due to “occult HBV infection” or due to a mutant HBV strain that results in non-reactive test for HBsAg.
  • There were at least 11 HBsAg assays that have been FDA-approved –most but not all of them will confirm results before reporting.

It is important to sort out patients with discrepant HBV serology.  In infants who are not identified with HBV testing (false-negatives), this results in suboptimal post exposure prophylaxis and increased likelihood of chronic HBV.  Whereas, infants with false-positive results, incur unnecessary prophylaxis and costs.  The authors note that “total anti-HBc was the most useful single test to resolve HBsAg discrepancies.

Also noted: J Pediatr 2014; 165: 767-72.  “Factors Affecting the Natural Decay of Hepatitis B Surface Antigen in Children with Chronic Hepatitis B Virus Infection during Long-Term Followup”  This study followed 349 Taiwanese children over 20 years and noted annual HBsAg clearance of 0.58% (42 cleared HBsAg).  Spontaneous clearance was more common in HBeAg-seroconverters, infants with low initial HBsAg level <1000 IU/mL, and to those born to non-HBsAg-carrier mothers.

What is Panayiotopoulos Syndrome?

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Recently, Panayiotopoulos syndrome was mentioned on the GI Listserv as a possible explanation for a child with seizures following vomiting and gagging.  I hope that I was not the only one to wonder what that was.

According to Pediatrics Review Article:

Panayiotopoulos syndrome is a common idiopathic childhood-specific seizure disorder formally recognized by the International League Against Epilepsy. An expert consensus has defined Panayiotopoulos syndrome as “a benign age-related focal seizure disorder occurring in early and mid-childhood. It is characterized by seizures, often prolonged, with predominantly autonomic symptoms, and by an EEG [electroencephalogram] that shows shifting and/or multiple foci, often with occipital predominance.”

Autonomic epileptic seizures and autonomic status epilepticus are the cardinal manifestations of Panayiotopoulos syndrome. Autonomic seizures in Panayiotopoulos syndrome consist of episodes of disturbed autonomic function with emesis as the predominant symptom. Other autonomic manifestations include pallor (or, less often, flushing or cyanosis), mydriasis (or, less often, miosis), cardiorespiratory and thermoregulatory alterations, incontinence of urine and/or feces, hypersalivation, and modifications of intestinal motility.

Bottomline: If a parent is convinced that vomiting or retching is triggering seizures, the child’s neurologist needs to consider this disorder.

Magnetic Resonance Elastography in Nonalcoholic Fatty Liver Disease

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A recent study (Hepatolology 2014; 60: 1920-8) shows that magnetic resonance (MR) elastography can be an accurate noninvasive tool to assess liver fibrosis.

Background: Assessing severity of liver fibrosis provides important prognostic information in patients with nonalcoholic fatty liver disease (NAFLD); however, these patients are often obese which decreases the success of transient elastography.  In addition, high hepatic fat content may alter the results of transient elastography.  Hence, an alternative noninvasive technique is desirable.

Design: Prospective study with 117 consecutive patients with biopsy-proven NAFLD who also underwent 2D-MR elastography between 2011-2013.

Results:

  • Fibrosis stage: stage 0 n=43, stage 1 n=39, stage 2 n=13, stage 3 n=12, stage 4 n=10.
  • MR elastography identified stage 3-4 with an accuracy of 0.92, with little overlap between advanced (F3-4) and non-advanced (F0-2) values.  The specificity, sensitivity, positive/negative predictive values, and cutoff values are detailed in Table 2.
  • Figure 3 provides a cool picture demonstrating the different MR elastography stiffness heat maps correlated with liver fibrosis. Link to similar web-based image from Siemens.

Bottomline: This technology allows a noninvasive measure of liver fibrosis in NAFLD patients and will probably be of use in other liver conditions.  Given the fact that a liver biopsy is more risky and often expensive, this technology and other noninvasive markers of advanced liver disease will be important tools.

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Lack of Meaningful Improvement in Crohn’s Patients with Tofacitinib

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As noted in a previous blog (see below for link), tofacitinib, an oral Janus Kinase Inhibitor has shown promise as an agent for ulcerative colitis. However, its results thus far for Crohn’s disease (CD) have been discouraging.  Another study (Clin Gastroenterol Hepatol 2014; 12: 1485-93) reiterates that message.

In brief, 139 patients with moderate-to-severe active CD were randomly assigned to 3 dosage groups of tofacitinib (1-, 5-, and 15-mg) and compared with placebo.  There were no significant differences in response or remission between tofacitinib and the placebo group, though there were reductions in both C-reactive protein and fecal calprotectin among patients given the 15-mg dose.

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Do Oral Nutrition Supplements Help Hospitalized Patients?

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A recent retrospective study suggests that oral nutrition supplements may shorten hospital stays and lower costs when matched against similar patients.

Here’s a link to the abstract: JPEN Oral Nutrition Supplement Study

Some of the details:

  • Retrospective analysis of 557,348 hospitalizations of children aged 2–8 years in the Premier Research Database
  • ONS were prescribed in 6066 of 557,348 inpatient episodes (1.09%).
  • ONS use was associated with a 2.9-day increase (95% confidence interval [CI], 2.32–3.39), or 51.6% increase in LOS, from 5.5 to 8.4 days. ONS use was also associated with increased episode cost of $8568
  • Using a matched sample of 11,031 episodes, hospitalizations with ONS use had 14.8% shorter LOS (6.4 vs 7.5 days). Hospitalizations with ONS use had 9.7% lower cost ($16,552 vs $18,320)

Bottomline: Despite the large numbers of patients, the retrospective nature of the study makes it difficult to determine whether these supplements are effective.  Only a randomized study can answer this blog’s title question.

What is the Role of Ursodeoxycholic Acid in Primary Sclerosing Cholangitis?

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While previous studies of ursodeoxycholic acid (UDCA) at high doses (28-30 mg/kg/day) have been shown to have detrimental effects, a number of randomized controlled trials (RCTs) have shown that low-dose UDCA has been associated with biochemical improvements but no differences in endpoints like death, liver transplantation or cholangiocarcinoma.  Given this conflicting information, a new study (Hepatology 2014; 60: 931-40, editorial 785-88) has examined the effects of withdrawal of low-dose UDCA.

In this cohort, the median age was 34 years, “62% were male, 69% had IBD, 19% had cirrhosis, and the baseline UDCA dose was 10-15 mg/kg/day.”

Key findings:

  • “At 3 months, discontinuation of UDCA in patients with PSC causes significant deterioration in liver biochemistry and influences concentrations of bile acid metabolites.”
  • Alkaline phosphatase increased 75.6%, GGT increased 117.9%, bilirubin increased by 50%, aspartate aminotransferase increased by 45.0%, and alanine amiontransferase increased by 63.9%
  • The Mayo Risk Score for PSC (associated with PSC prognosis) also increased 0.5 points from baseline.

Conclusion (from editorial): “there may still be a role for judicious use of UDCA in patients with well-compensated disease.”  A suggested “yet unproven” algorithm for use of UDCA is noted in Figure 1 pg 787 and considers UDCA for patients with alkaline phosphatase >1.5x ULN and/or PSC-associated symptoms like pruritus.  If no clinical improvement within 6 months, then stopping UDCA is recommended.

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Liver Disease Associated with Inflammatory Bowel Disease

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A useful review on the hepatobiliary manifestations of inflammatory bowel disease (IBD): Inflamm Bowel Dis 2014; 1655-67.

A few topics/comments from review:

Primary sclerosing cholangitis (PSC):

  • “among those with PSC, about 70% to 80% have UC and 15% to 20% have CD.  Those IBD patients with PSC are more likely to develop malignant complications and to require liver transplantation. Conversely, only about 0.4% to 7.5% of patients with IBD will develop PSC.”
  • “Currently, no medical treatment has been proven to decrease the progression of PSC.”
  • “At the time of diagnosis of PSC, IBD must be ruled out and a complete colonoscopy with multiple segmental biopsies of the mucosa needs to be performed.”  Among PSC-IBD patients, “annual surveillance colonoscopy is recommended.”
  • Further surveillance recommendations (eg. annual imaging/CA 19-9 annually) discussed in Table 2.

Cholelithiasis: Gallstones are reported in 13% to 24% of all patients with CD.  In UC, the risk of cholelithiasis “does not seem to be increased.”

Drug-induced liver disease: (see liver tox website)

  • Thiopurines
  • Methotrexate
  • Sulfasalazine/mesalamine
  • Biologic agents

Viral hepatitis in immunosuppressed IBD patients:

Hepatitis B reactivation -algorithm for screening/management of latent hepatitis B provided in Figure 3

Other liver problems seen in IBD patients:

  • Portal Vein Thrombosis
  • Nonalcoholic Fatty Liver Disease
  • Secondary amyloidosis
  • Hepatic abscess

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Work on Both Ends

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Two articles provide some insight into endoscopic interventions on both ends of the gastrointestinal tract.

In the first article (JPGN 2014; 59: 608-11), the authors retrospectively studied 11 children who received mitomycin-C concurrently with endoscopic dilatation for the treatment of anastomotic strictures after esophageal atresia repair.  Key finding: 8 of 11 achieved resolution of their strictures, 2 remained with stenosis, and 1 needed surgical correction. However, the authors found no benefit of mitomycin C in the resolution of the strictures compared with endoscopic dilatation alone in historical controls (n=10). In fact, in this small study, the control group patients had fewer endoscopic dilatations (3.7 vs. 5.4 dilatations per patient) and 9 of 10 achieved stricture resolution.

In the second article (JPGN 2014; 59: 604-08), the authors retrospectively reviewed the outcome of children (n=33) with surgically-treated Hirschsprung’s disease (HD) who were treated with intrasphincteric Botox injections for obstructive symptoms. In these children with median age of first Botox injection was 3.6 years; a median of 2 injections were given.  26 (79%) had had a transanal endorectal pull-through.  Key finding: initial improvement was noted in 76% and “good/excellent” long-term response was evident in 52% (Table 2).

Bottomline: Botox therapy appears helpful for non-relaxing sphincters in HD whereas mitomycin-C remains an unproven therapy for esophageal strictures.

Also briefly noted: JPGN 2014; 59: 674-78.  “Use of cyproheptadine in young children with feeding difficulties and poor growth in a pediatric feeding program.” n=127.  Of the 82 who took cyproheptadine regularly, 96% reported a positive change in feeding behaviors and there was a significant improvement in weight gain.

Also, with regard to stooling problems, Sana Syed (Emory GI fellow) pointed out a useful website that emphasizes proper positioning for functional constipation: squattypotty.com.  While the website promotes their product to provide proper foot support (with elevation), there are other ways to get a similar result.  As noted previously (“Poo in You” Video | gutsandgrowth) proper positioning can help a lot.

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Rough Skin -Tough Case

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Briefly noted:

“D is Delay” NEJM 2014; 371: 2218-23.  This case presentation described how a 47-year-old homeless man presented with a neuropathy and over the course of FIVE YEARS developed dermatitis, diarrhea, and dementia.  Ultimately, he was diagnosed with niacin deficiency or pellagra. It is almost painful reading the case report knowing how long it took to establish the diagnosis. Take home points from this case report:

  • Pellagra is derived from the Italian pelle agra which means “rough skin”
  • Nutritional deficiencies are difficult to diagnose in this country due to their rarity/lack of pattern recognition