How Birth Can Affect Your GI Tract

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A recent review (JPGN 2013; 57: 543-49) provides information about the relationship between neonatal environment and subsequent inflammatory gastrointestinal disease.

While most of the review, focuses on physiology and pathophysiology, the most interesting part is the assertions (with references) in Table 1 which include the following:

  • Breastfeeding reduces risk of IBD
  • Cesarean section increases the risk of celiac disease, cow’s milk allergy, and other IgE-mediated food allergies
  • Many chronic adult diseases have been shown to have origins in neonatal life, particularly cardiovascular disease/metabolic syndrome

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Wiping out Hepatitis C

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Here’s the view of the NY Times (nyti.ms/1b7nTbl ) about the new therapies for Hepatitis C:

Medicine may be on the brink of an enormous public health achievement: turning the tide against hepatitis C, a silent plague that kills more Americans annually than AIDSand is the leading cause of liver transplants. If the effort succeeds, it will be an unusual conquest of a viral epidemic without using a vaccine.

“There is no doubt we are on the verge of wiping out hepatitis C,” said Dr. Mitchell L. Shiffman, the director of the Bon Secours Liver Institute of Virginia and a consultant to many drug companies.

Over the next three years, starting within the next few weeks, new drugs are expected to come to market that will cure most patients with the virus, in some cases with a once-a-day pill taken for as little as eight weeks, and with only minimal side effects.

That would be a vast improvement over current therapies, which cure about 70 percent of newly treated patients but require six to 12 months of injections that can bring horrible side effects.

The latest data on the experimental drugs is being presented at The Liver Meeting in Washington, which ends Tuesday [11/5/13]

But the new drugs are expected to cost from $60,000 to more than $100,000 for a course of treatment.

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45,000 Unnecessary Deaths Per Year

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According to a recent editorial (NEJM 2013; 369: 1180-81), 45,000 American adults die each year because they have no medical coverage (Am J Public Health 2009; 99: 2289-95).

The editorial which describes a late diagnosis of colon cancer in an adult who had been chronically uninsured despite working full-time makes a couple of key points:

  • Lack of insurance can be lethal
  • Underinsured also have higher mortality rates  One example: insurance status, not race, was associated with mortality after an acute cardiovascular event in Maryland (J Gen Intern Med 2012; 27: 1368)

While the rollout for the Affordable Care Act (ACA) has been bad, the underlying reason for it remains sound.  In addition, though the ACA expands coverage, I am skeptical that it will control problems with skyrocketing costs.  As such, many other difficult changes in medical care delivery will ultimately be needed.

Related blog post:

Life in the balance (book) | gutsandgrowth

Predicting Severe Clostridium Difficile

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According to a recent publication (Clin Gastroenterol Hepatol 2013; 11: 1466-71), the most important risk factors for severe Clostridium difficile infection (CDI) are the following:

  • Peripheral leukocytosis (WBC >15,000)
  • Elevated serum creatinine >1.5 times baseline
  • Narcotic use
  • Acid-blocking medications
  • Older age

This study reviewed the records of inpatient cases at the Mayo clinic between 2007-2010. In total, 487 of 1446 patients had severe CDI, defined as ICU admssion (26.7%), colectomy (2.7%) or death (8.9%) within 30 days of diagnosis.

Patients with these risk factors may need to be treated more aggressively.

Also, noted: Am J Gastroenterol 2013; 108: 1794-1801. (Thanks to Ben Gold). Using electronic medical records, the authors identified 894  adult inpatients with a first-time CDI (2009-2012).  Receipt of PPIs concurrent with CDI treatment was not associated with CDI recurrence.

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Primary Enteric Nervous System Disorders

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If you are wondering what these are, you may want to review a recent consensus statement (JPGN 2013; 57: 677-86).

This ‘practical guide’ discusses Hirschsprung’s disease, intestinal neuronal dysplasia, chronic intestinal pseudo-obstruction, ultrashort segment Hirschsprung’s disease, hypoganglionosis, and ganglioneuromatosis in MEN 2B.

Most of the focus is on Hirschsprung’s disease including the intricacies of diagnosis, clinical presentation, and genetics.  While the authors do mention the PHOX2B gene and others, there is not a discussion of Ondine’s curse (Congenital central hypoventilation syndrome and Hirschsprung’s …).  One point that I think is important (but not discussed in the above reference) in patients who have Ondine’s curse and Hirschsprung’s is determining whether a family member may have a milder phenotype that could still place them at risk for sudden death (eg. after a simple sedation procedure).

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What is calretinin? | gutsandgrowth

Liver Biopsy -Risks and Benefits

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Even in the ‘old USA,’ there is a mortality risk from liver biopsy in the pediatric population.  A recent study from Los Angeles confirms this (JPGN 2013; 57: 644-48).

This retrospective review of all children (n=213 children & 328 biopsies) who underwent a percutaneous liver biopsy between 2008-2011 were examined.  These biopsies were completed by radiology with ultrasound or CT.  Gel foam was injected in cases of multiple biopsies.

Results:

  • 9 (4.2%) dropped hemoglobin > 2 /dL.
  • 7 (3.3%) needed a transfusion.
  • 1 (0.5%) died.  This was a 2.6 kg infant seen for transplant evaluation.
  • 63 (19%) had insufficient samples for definitive histologic evaluation.
  • In 81% of initial biopsies, “a definitive pathologic diagnosis was obtained.”
  • Biopsies for unexplained elevation of liver function tests were nondiagnostic in 34.9%.

The authors take: “our data demonstrate that percutaneous liver biopsy is generally safe; yet, finite risk remains, with bleeding-related complications occurring 5.2% of children.”

Bottomline: make sure you need the information from the liver biopsy enough to justify the risk, particularly in small children and in those at increased risk for bleeding.

Related blog post (with annotated references):

Liver biopsy risk in children | gutsandgrowth

Don’t Go Nuts over Nuts

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A recent study (NEJM 2013; 369: 2001-11) showed that nut consumption was associated with a lower mortality rate among more than 115,000 people in two large independent cohorts.  Nut consumption had significant inverse associations with deaths due to cancer, heart disease, and respiratory disease.  Those who ate nuts most frequently (7 or more times per week) had a 20% lower hazard ratio for death. However, the individuals who consumed nuts may have been more likely to have other healthy habits, though this was not identified in the study.

This study is explained more fully in the following video (less than 3 minutes):  nej.md/1aSbuY4 

Have you seen the Duodenal-Jejunal Bypass Liner?

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A recent article (Clin Gastroenterol Hepatol 2013; 11: 1517-20) reports on the effects of the duodenal-jejunal bypass liner (DJBL) on improvement in parameters of nonalcoholic liver disease (NAFLD).  The study enrolled 17 patients who had obesity and type 2 diabetes mellitus.

The following link provides more details on this technique (from a 2009 study) and provides a picture (Figure 2) of the 60 cm sleeve that is placed endoscopically:

Radiographic appearance of endoscopic duodenal … – GI Dynamics

These studies indicate that less invasive approaches may develop as alternatives to bariatric surgery.

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Explaining the Vitamin D Paradox

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For a long time, there has not been a satisfying explanation for the fact that blacks have higher bone mineral density but lower 25-hydroxy-vitamin D levels than whites.  New research (NEJM 2013; 369: 1991-2000, editorial 22047-48) helps explain this paradox.

This study examined a community cohort of 2085 individuals in the “Healthy Aging in Neighborhoods of Diversity across the Life Span” study.

Key Findings:

  • Blacks had higher bone mineral density and lower 25-hydroxy-vitamin D levels than whites
  • The calculated bioavailable levels of 25-hydroxy-vitamin D were similar to whites.

The editorial notes that the similar bioavailability is due to differences in the vitamin D-binding protein (aka GC-globulin).  “GC1F is the most abundant form in persons of African ancestry whereas GC1S is most abundant in European populations.”  Thus, it has been hypothesized that the vitamin D-binding protein in blacks has “increased affinity for vitamin D3, and thus able to transport vitamin D3 more efficiently from the skin to the liver for its metabolism to 25-hydroxy-vitamin D.”

Bottomline: This research in vitamin D metabolism may impact on how we determine vitamin D deficiency.  The measurement of vitamin D-binding protein may need to be incorporated into the assessment.

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Progression of Hepatitis C in Children

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A retrospective study (Hepatology 2013; 58: 1580-86) of liver biopsies from treatment-naive children enrolled in the PEDS-C study confirm the perception that hepatitis C histologic progression is typically slow.

This study examined 35 pediatric patients (84% genotype 1) who had at least two liver biopsies more than a year a part at eight different centers.  For this study, all of the liver histology was scored by a single pathologist.  Mean age at first and final biopsy were 8.6 and 14.5 years.  Mode of transmission: 57% vertical and 39% transfusion.

Results:

  • Inflammation was minimal in about 50% at both timepoints.
  • Fibrosis was absent in 16% at both timepoints.  Fibrosis was limited to portal/periportal in 73% at first biopsy and 64% at second.
  • Proportion of patients who had bridging fibrosis/cirrhosis at second timepoint increased from 11% to 20%.  Overall, 29.5% (n=13) showed an increase in severity of fibrosis.
  • In aggregate, “this cohort did not show significant histologic progression of liver disease over 5 years.”

Implications for treatment per authors: “It may be argued that treatment of a slowly progressing disease in an asymptomatic child may be deferred given the side effects and limitations of the currently available therapy. On the other hand, some might favor early treatment…a liver biopsy …may influence decisions regarding therapy.”

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