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About gutsandgrowth

I am a pediatric gastroenterologist at GI Care for Kids (previously called CCDHC) in Atlanta, Georgia. The goal of my blog is to share some of my reading in my field more broadly. In addition, I wanted to provide my voice to a wide range of topics that often have inaccurate or incomplete information. Before starting this blog in 2011, I would tear out articles from journals and/or keep notes in a palm pilot. This blog helps provide an updated source of information that is easy to access and search, along with links to useful multimedia sources. I was born and raised in Chattanooga. After graduating from the University of Virginia, I attended Baylor College of Medicine. I completed residency and fellowship training at the University of Cincinnati at the Children’s Hospital Medical Center. I received funding from the National Institutes of Health for molecular biology research of the gastrointestinal tract. During my fellowship, I had the opportunity to work with some of the most amazing pediatric gastroenterologists and mentors. Some of these individuals included Mitchell Cohen, William Balistreri, James Heubi, Jorge Bezerra, Colin Rudolph, John Bucuvalas, and Michael Farrell. I am grateful for their teaching and their friendship. During my training with their help, I received a nationwide award for the best research by a GI fellow. I have authored numerous publications/presentations including original research, case reports, review articles, and textbook chapters on various pediatric gastrointestinal problems. In addition, I have been recognized by Atlanta Magazine as a "Top Doctor" in my field multiple times. Currently, I am the vice chair of the section of nutrition for the Georgia Chapter of the American Academy of Pediatrics. In addition, I am an adjunct Associate Clinical Professor of Pediatrics at Emory University School of Medicine. Other society memberships have included the North American Society for Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN), American Academy of Pediatrics, the Food Allergy Network, the American Gastroenterology Association, the American Association for the Study of Liver Diseases, and the Crohn’s and Colitis Foundation. As part of a national pediatric GI organization called NASPGHAN (and its affiliated website GIKids), I have helped develop educational materials on a wide-range of gastrointestinal and liver diseases which are used across the country. Also, I have been an invited speaker for national campaigns to improve the evaluation and treatment of gastroesophageal reflux disease, celiac disease, eosinophilic esophagitis, hepatitis C, and inflammatory bowel disease (IBD). Some information on these topics has been posted at my work website, www.gicareforkids.com, which has links to multiple other useful resources. I am fortunate to work at GI Care For Kids. Our group has 17 terrific physicians with a wide range of subspecialization, including liver diseases, feeding disorders, eosinophilic diseases, inflammatory bowel disease, cystic fibrosis, DiGeorge/22q, celiac disease, and motility disorders. Many of our physicians are recognized nationally for their achievements. Our group of physicians have worked closely together for many years. None of the physicians in our group have ever left to join other groups. I have also worked with the same nurse (Bernadette) since I moved to Atlanta in 1997. For many families, more practical matters about our office include the following: – 14 office/satellite locations – physicians who speak Spanish – cutting edge research – on-site nutritionists – on-site psychology support for abdominal pain and feeding disorders – participation in ImproveCareNow to better the outcomes for children with inflammatory bowel disease – office endoscopy suite (lower costs and easier scheduling) – office infusion center (lower costs and easier for families) – easy access to nursing advice (each physician has at least one nurse) I am married and have two sons (both adults). I like to read, walk/hike, bike, swim, and play tennis with my free time. I do not have any financial relationships with pharmaceutical companies or other financial relationships to disclose. I have helped enroll patients in industry-sponsored research studies.

Pediatric NAFLD Position Paper

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A previous blog post (NAFLD Guidelines 2012) described comprehensive, up-to-date NAFLD guidelines from AASLD, AGA, and ACG.   Another group of experts from ESPGHAN (European Society for Pediatric Gastroenterology, Hepatology, and Nutrition) has also published a position paper on the diagnosis of NAFLD in children; coincidentally, these were published recently as well (JPGN 2012; 54: 700-13).

While there is some overlap in the information between the two guidelines, there are some notable differences.  The JPGN manuscript does include a nice differential diagnosis list  which can cause fatty liver disease (Table 2), including some rare entities like Dorfman-Chanarin syndrome, Cantu syndrome, Madelung lipomatosis, and numerous medications.  This review has more emphasis on etiology.

Table 3 lists a recommended workup in children with suspected NAFLD:

  • Standard liver function tests/blood counts/coagulation studies
  • Fasting glucose & insulin
  • Lipid profile
  • Glucose tolerance test & glycosylated hemoglobin
  • Calculation of HOMA-IR, markers of insulin resistance

AND Tests to exclude other liver diseases: 

  • Lactate, uric acid, iron, ferritin, pyruvate
  • Copper, ceruloplasmin, 24-hour urinary copper
  • Sweat test
  • Celiac serology (TTG IgA and serum IgA)
  • α-1-antitrypsin levels and phenotype when indicated
  • Amino and organic acids
  • Plasma free fatty acids and acyl carnitine profile
  • Urinary steroid metabolites
  • Other specific tests as suggested by evaluation (eg. viral hepatitis panel, serum immunoglobulins, liver autoantibodies)

When one looks at the recommended diagnostic algorithm (Figure 1) and tests outlined, these guidelines are not nearly as practical as the NAFLD guidelines from AASLD, AGA, and ACG and often contradictory between the tables/figures and the text.  How much would it cost for the recommended testing if/when extrapolated to the vast numbers of individuals with these disorders?  In addition, a much more limited diagnostic approach is suggested in the final section than outlined in Table 3 and Figure 1.

Imaging: these authors advocate LFTs and ultrasonography in all obese children (> 3 years) and adolescents.  If normal LFTS and sonography, the algorithm suggests the use of MRI if clinical signs of insulin resistance.  Later, the authors conclude “MRI is not cost-effective.”

Liver Biopsy: while the authors state that there is “no present consensus or evidence base to formulate guidelines” for liver biopsy, this is not well-reflected in their diagnostic algorithm in which arrows point to liver biopsy in almost everyone –either early liver biopsy or eventual biopsy in patients with persistent disease.  Accepted liver biopsy indications, according to the executive summary, include the following:

  • Exclude other treatable disease
  • Suspected advanced disease
  • Before pharmaceutical/surgical treatment
  • Research purposes

My conclusion about this position paper is it is less helpful than the AASLD/AGA/ACG guidelines.  In fact, when extensive diagnostic testing is recommended by experts, it is fortunate that other expert guidelines are available that support a more cost-effective approach.  In NAFLD cases that seem atypical and especially in the very young patient, this reference may still be helpful.

Geographic Inequity for Liver Transplantation

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Organ scarcity remains a big problem for liver transplantation.  Use of the Model for End-Stage Liver Disease (MELD) score was intended to address inequity in liver transplantation allocation.  However, it has not been successful.  One recent study which examines donation after cardiac death versus brain death (Liver Transpl 2012; 18: 630-40) also yields some insight into liver transplantation allocation across the U.S.

In Figure 3, the thirty-day probability of receiving a liver transplantation (brain death donation) for patients with MELD score >20 was compared across UNOS regions.  In regions 3 and 11 (Southeastern U.S. extending to Kentucky and Virginia), the rate was ≥40%.  In region 1 (Northeastern U.S) and region 5 (Southewestern U.S.) , the rates were 9.6% and 11.8% respectively.  Thus, some patients with the exact same MELD score have a 4-fold higher probability of receiving a liver transplant.

Related blogs:

Alive and well? 10 years after liver transplantation

Picking winners and losers with liver transplantation allocation

Big gift, how much risk

Sarcopenia, fatigue, and nutrition in chronic liver disease

Best gastrostomy tube

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A recent report touts the feasibility of a one-step percutaneous gastrojejunostomy (GJ) as the latest advance in enteral access (JPGN 2012; 54: 820-21).  This reference describes a new variation in technical placement: gastropexy using t-fasteners to secure gastrostomy tube site and then advancing neonatal scope via gastrostomy site to advance guidewire for  GJ placement.  This technique was used in three infants.

Most centers have developed their own protocols for enteral access and it is likely that the familiar approach to that center will be safest for their patient population.  Recently, the subject of gastrostomy tube placement was extensively reviewed in our institution (see below) due to variation in care at two children’s hospitals.  In one hospital, the surgical group primarily placed laparascopic button gastrostomies and argued that better visualization led to lower complications like colonic interposition.  Furthermore, this approach was considered similar in cost effectiveness as the group would place a primary Mic-Key® (http://www.mic-key.com/home.aspx) thereby eliminating the need for anesthesia for a button placement.

The alternative approach utilized a Corflo® gastrostomy tube (http://www.corpakmedsystems.com/product_main/enteral_main.html#FeedingTubes).  The advantages of this approach were 1) less anesthetic time/a smaller operation, and 2) lower likelihood of tube dislodgment.  This group approach argued that dislodgment was the greatest risk and that there was no urgency for a button tube.

Despite a joint meeting of these groups weighing the pros and cons, there was not a single best gastrostomy tube.

My experience is that tube dislodgment is quite common with button tubes.  In addition, primary button tubes can be difficult to size when the patient is under anesthesia.  As such, it is my practice to discourage primary gastrostomy button placement.  In addition, most patients who need gastrostomy tubes can wait until they are good surgical candidates both in terms of cardiorespiratory status and size.

Resources:

Gtube Products:
• AMT clamp –helps eliminate tubing pullouts
www.amtinnovation.com

• Gtube washable pads
www.oley.org  (specific web address: http://oley.org/lifeline/TubetalkJF11.html)

Additional references:

  • -J Pediatr 2011; 159: 602. Preemptive gtube assoc with improved survival post Norwood. High number needed fundoplication.
  • -JPGN 2011; 53: 293. 95% success with PEG in infants 2.1-5.6kg
  • -JPEN 2011; 35: 50-55. Predictive factors of mortality after PEG.
  • -JPGN 2009; 49: 237. Gtube improves height & weight in Rett syndrome.
  • -Clin Gastro & Hep 2007; 5: 1372. PEG placement does NOT prolong life in dementia patients.
  • -Arch Dis Child 2006; 91: 478-82. PEG reduced hospitalizations for respiratory dz in 57 severely impaired children
  • -J Pediatr 2006; 149: 837. inreased risk of PEG in SMA type 1 -42% w aspiration; 17% death (2/12)
  • -Pediatrics 2004; 114: 458-61. Moratlity rate of 0.4% -one death related to sepsis/peritonitis & 5% complication rate.
  • -Teitelbaum JE, Gorcey SA, Fox VL. Combined endoscopic cautery and clip closure of chronic gastrocutaneous fistulas. Gastrointest Endosc. 2005;62(3):432-435
  • -JPGN 2006; 43: 624. Satisfaction with PEGs: 94% of parents viewed PEG as positive influence on child’s situation & 98% would have chosen PEG insertion again (n=121).
  • -Sullivan PB, Dev Med Child Neurol 2005; 47: 77-83. 57 CP pts -almost all had improved health/nutrition p gtube
  • -Gastroenterology 2001; 121: 970-1001 & JPEN 2004; 28: S16. Provision of nutrition does not, for the most part, favorably alter clinical outcome.
  • -Lancet 2005; 365: 755-763. Pts c stroke/PEG did not do better than those c stroke/NGT.
  • -Sullivan PB, Dev Med Child Neurol 2004; 46: 796-800. gtube improves QOL.

Gastrostomy Tube Review with annotated references: Laparoscopic gtube versus conventional PEG placement

 Zamakhshary et al.  JPS 2005; 40: 859-62.   i.  Retrospective review, n=119 (only 26 with laparoscopy =21%). (2002-2003)  ii.  States same operative time of ~53 min by combining 2nd procedure w PEG (in 77% w PEG).  It takes these authors a long time to perform PEG and gtube change procedures.  Also, it is not noted how many of these 2nd procedures were coordinated with other needed anesthesias.  (Many times a PEG is replaced at the time of another procedure.)   iii.   3 PEG with transcolonic tube, 2 failed PEG –one with peritonitis, 4 with tract disruption when PEG pulled.  Similar rate of local problems (eg granulation tissue).  ARTICLE does not detail when PEG tubes are pulled –VERY high rate of tract disruptions.   iv. Article missing key details regarding size of PEGs & gtube buttons which may impact complications.  v. Cited advantages according to authors:

  1. “eliminates” risk of hollow viscus injury (JH: this is NOT  accurate)
  2. Useful for small infants (<2kg) (JH: usually gtube NOT needed in <2kg)
  3. Enables “ideal” location (JH: this is NOT  accurate)
  4. Primary button ‘advantage’ (JH: DOES NOT cite potential pitfalls like button too tight, possibility of balloon breakdown, possibly higher rate of dislodgment)

 Vervloessem et al. JPS 2009; 18: 93-97.     i. Retrospective review: 1992-2008.  N=467.  ONLY 19 Lap PEG –thus limited ability to provide comparison.  ii. Cites 59 “major complications” due to PEG –Table 2, including “13” new cases of GERD after PEG (or worsened GERD).  Of the major complications, important complications included 1 sepsis death, 7 peritonitis, 5 gastrocolic fistulas, 4 major granulation tissue, and 11 buried bumpers.  iii.  States that VPS is risk factor for infection but does not state whether any Lap gtubes were done in these patients.  iv. Complication rate decreased over the years—p=0.003; thus PEG procedure became safer with time and experience.   Could not demonstrate a decrease in complications with lap gtube versus PEG.  Authors recommend lap PEG in specific situations such as previous abdominal surgery or if not a good puncture site.

 Segal et al. JPGN 2001; 33: 495-500.    i. Retrospective study, n=110 (1990-97). N=110 –ALL PEG (no LAP). Thus, limited utility in comparing two methods. ii. “44%” developed late complications with PEG.  Most common: 24 extruded tubes/buried tubes (would NOT be better with lap button); other important: cologastric fistula n=2, peritonitis.  Table 1 indicates that 75% of dislodgment were due to buttons not PEG.  12 of the complications were granulation tissue and proliferative gastric mucosa.  Buried tubes occurred 14 & 19 months after placement with button tube!!   iii.  Thus this article adds little to the discussion of PEG vs lap gtube.

Akay et al. JPS 2010; 45: 1147-52  i.  Retrospective review (2004-2008) n=238 (134 PEG, 104 LAP)  ii. PEG with higher complications;  authors were changing PEG after 6-8 weeks. iii.  6 patients had early PEG dislodgment –this is higher than expected.  iv. 1 patient with gastrocolic-cutaneous fistula with both PEG & with LAP.  v. Table 4 lists complications: similar stomal issues, 2 patients with leak after PEG exchange (too early! –see page 1152) vi. Cited advantages: “eliminating” risk of hollow viscus injury, allows for sutures, small infants (<2kg) & possible primary buttons.**These authors did not place primary buttons –this makes it difficult to draw any conclusions about PEG vs primary LAP button.  Many feel PEG tube is a better tube and less prone to dislodgment than button and guarantees appropriate size.

Lantz et al. Int J Pediatr 2010; ID# 507616, 1-4.   i. Literature review, included 54 studies that qualified (1995-2009).  N=4331 (1027 LAP, 3304 PEG).  Very few details given in this review.  ii.Fistulas in 1.27% of PEG vs 0% for LAP.  iii.  Lists significant limitations: different studies, not blinded, nonpublication bias.  iv.  “This study highlights the need …for trials, comparing PEG to” LAP. v.  Does not include the limitation that LAP technique developed later and with more experience less complications.  Except for gastrocolic-cutaneous fistulas –no specific information is given about complications.

Avitsland et al.  JPGN 2006; 43: 624-28.  i. Restrospective review. N=121 –all PEGs  ii.     PEG “safe technique…major complications rare.”  “Most children experience minor stoma-related complications.”  iii. 29 died due to other factors.  Of 85 with f/u, 21 able to remove gastrostomy.  iv. No early mortality (<30 days).  1 of 85 had tube dislodgment.  3 had tube migration into esophagus (in cases where tube was not endoscopically removed).  v.     Frequent tube site problems ~75% -most easily treated. vi. Parents with high satisfaction: 83/85 (98%) would choose PEG again, 80/85 (94%) stated PEG improved child’s situation

Gauderer M. JPS 2001; 36: 217-19.   i.  Focused literature search and personal 20 year experience. ii. >216,000 PEGs performed annually in U.S. according to article (~5000 children).  PEG procedure developed 1st for children. iii.  Suggested approach to PEG with or w/o fundoplication: “Because PEG is such a simple procedure, a well-accepted approach is to place gastrostomy initially in children who can tolerate nasogastric tube feedings and add an antireflux procedure later, if needed.”

Srinivasan et al. JPGN 2009; 49: 584-88.   i.Prospectively collected data from observational study, n=601 (384 PEG insertions, 165 button conversions).  ALL pediatric. ii.  Complications:  PEG site erythema 15%, buried bumper migration (1 patient), 3 PEG dislodgments, one patient had laparotomy due to severe pain (no findings identified).   No procedure-related mortality.   iii.  49 of 384 removed –no longer needed.  iv. “The role of PEG is well established…our experience..PEG has been generally safe, with low procedure-related morbidity in children.”

Nutr Clin Pract 2005; 20 (6): 607-12.  Bankhead RR et al. i. Comparison of 91 patients.  23 PEG, 39 LAP, 29 open.  ii.   PEG had lowest complication rate

Surg Endosc 2006; 20: (8): 1248-51.  Ljungdahl M.                                         i.     Prospective, randomized study. N=70.  ii.  PEG with lower complication rate than surgical (open) gastrostomy –lower mortality & morbidity in adult patients.

UK Review Online: http://www.patient.co.uk/doctor/PEG-Feeding-Tubes-Indications-and-Management.htm   2009  i. Review of alternatives to PEG for gastrostomy insertion. There are alternative methods of gastrostomy tube insertion to PEG. They are: a) Laparoscopic insertion b) Open surgical technique c)Percutaneous radiologically guided gastrostomy (PRG) insertion. ii.  “There are reports over the years since introduction of PEG in the 1980s with often inconclusive results.21▪    A small study from Ireland and one from London favour PRG in patients with amyotrophic lateral sclerosis as it avoids the need for sedation or endoscopy.22,23▪  One meta-analysis suggested a higher success rate with PRG than with PEG, and less morbidity than either PEG or surgery.24 However a more recent comparison of a relatively small number of endoscopic, surgical and laparoscopic placement favoured PEG25 and another favoured PEG over PRG.26▪     A literature review suggested PEG as the procedure of choice for placement of gastrostomy tubes.27▪    A recent prospective randomized trial favoured PEG over surgical gastrostomy insertion.28▪     There is some evidence that polyurethane PEGs are less troublesome than silicone PEGs (less tube deterioration, less blockage).29▪    PEG is preferred in trauma patients.30▪                Antibiotic prophylaxis for PEG insertion appears to reduce the incidence of wound infection.19,20▪      Laparoscopic insertion was considered preferable to PEG by one study in children with PEG insertion having higher complication rate in children and often requiring repeat anaesthetics.31   An earlier study in children showed similar results for surgical, PRG and PEG insertion but did not look at the laparoscopic technique.32    A recent study from Norway found PEG insertion safe and very well tolerated by children and parents but made no comparison with other techniques.

Conclusions of review: PEG likely increases risk of gastrocolic fistulas (1-2%) but this has been reported with LAP as well.  The incidence is low.  No well-designed  studies have demonstrated superiority of LAP over PEG in terms of safety.  Potential drawbacks of LAP are likely underreported.  There have been cases of severe peritonitis at local hospitals following lap with primary gtube balloon misplacement.  Many feel PEG tube is a better tube and less prone to dislodgment than button (dislodgment is most frequent serious adverse event) and can be easily adjusted to  appropriate size.  To minimize complications, tube should not  be changed early.

Natural laws not patentable: the case with Prometheus

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While most individuals might think of greek mythology or the recent movie when hearing the word “Prometheus,” pediatric gastroenterologists might think of the company that performs a number of useful diagnostic tests.  Recently, Prometheus has had a legal setback (NEJM 2012; 365: 2338-40). 

Since the 1990s, Prometheus has tested for azathioprine (& 6-mercaptopurine) metabolites.  A therapeutic level of 6-thioguanine (6-TG), a metabolite for these drugs, is recognized as generally between 230-400 pmol per 8×10(to the 8th) red cells.  Levels outside this range often require drug adjustments.

When the Mayo clinic started to offer a slightly different assay, priced 25% below Prometheus’s test, Prometheus sued for patent infringement.  The court held that “if a law of nature is not patentable, then neither is a process reciting a law of nature;”  hence, Prometheus’s patent was rejected.

There are implications of this lawsuit on the use of a large number of biomarkers.  For example, patents for BRCA DNA sequences that increase the risk for cancer will probably be overturned.  Industry groups argue that denying patents will halt progress as companies will not be able to recoup investments in biomarker development.  Congress could consider passing laws allowing exclusive marketing of these innovations.  Alternatively, adequate funding through the NIH (National Institutes of Health) could allow development of biomarkers without the need for patents; in fact, 100 projects are in progress at this time.

Is obesity neglect?

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Usually not –according to a thoughtful commentary on this controversial topic (J Pediatr 2012; 160: 898-99).

Suggested criteria for child removal:

  • 1. High likelihood for serious and imminent harm
  • 2. Reasonable likelihood that coercive intervention will be effective
  • 3. Absence of alternative options for addressing the problem

However, “allowing a child to lose all opportunity to live into healthy adulthood when effective treatment is available runs contrary to the central mission of child rearing…When this occurs, regardless of the cause, it must be all about the child, and something must be done.”

Related blog posts:

Treating diabetes with surgery

Lower leptin with physical activity

Staggering cost of obesity

Additional references:

Assessing and discussing risk of lymphoma in IBD

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A recent article has shown that the absolute lymphoma risk from medications in children and young adults with IBD is quite low (Inflamm Bowel Dis 2012; 18: 838-43).

In this single center study from 1979-2008, 1374 pediatric IBD patients had charts reviewed to determine whether lymphoma developed.  In total, two male patients who had received thiopurines developed lymphoma (one Hodgkin, one anaplastic large cell) in 6624 patient-years of follow-up.  Both patients are alive after chemotherapy.  Mean follow-up was 4.8 years per patient.  The absolute lymphoma incidence rate was 3 per 10,000 patient-years; after thiopurine exposure, the rate was 4.5 per 10,000 patient-years compared to an expected 0.58 per 10,000 patient-years.

In this study, 22% of the patients had received TNF inhibitors.  None developed lymphoma.  The risk of biologics could not be fully assessed due to a limited study period: 713 person-years taking the medication.

The risk of thiopurine-associated lymphoma was similar to previous studies but did not reach statistical significance.  As related in other studies, the risk of biologic agents, like Remicade, Humira, and Cimzia, is heavily influenced by whether patients had also received immunomodulators.

One useful way to try to convey this risk has been with diagrams.  One useful diagram is a palette of one thousand people or of 10,000 people showing the absolute risk and one showing the risk for other complications like infection.  You can make your own by going to the following link:

Download Communication Tools

RiskComm

Additional references/blog entries:

Only one chance to make first impression

Biologics | Living Longer | Arthritis Today Magazine -From Arthritis magazine: biologics improve survival in Rheumatoid arthritis

Why “therapeutic dose” of codeine can kill

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While this blog has described some of the huge problems with the overuse of narcotics (Deadly consequences of pain management), another danger with narcotics occurs especially with codeine due to its metabolism via the CYP2D6 pathway; codeine is particularly risky in young children.  A reminder of this is a recent case report (Pediatrics 2012; 129: e1343-1347).

During my training, I was told by an ENT doctor that he never prescribed codeine in children less than 6 years of age due to safety concerns.  While he could not explain the mechanism, this case report does.  This case report describes three children with severe cases (two were fatal) from North America.  In the two fatal cases, gene duplications encoding Cytochrome P450 2D6 (CYP2D6) caused a significantly greater production of morphine from its parent drug, codeine.  This risk of respiratory depression may be enhanced in ENT cases especially in children with obstructive sleep apnea.

The risk from codeine involves individuals who are ‘ultra-metabolizers’ of CYP2D6; this is because the metabolized drug in this case, morphine, is more potent than the parent drug, codeine.  Other opioids that are similar to codeine, like hydrocodone and oxycodone, may have additional risk as well.  Ultra-metabolizers include up to 7% of all caucasians.  In addition, 5-10% of caucasians are poor-metabolizers which would result in a lack of therapeutic effect with codeine.

While ultra-metabolizers of CYP2D6 function are prone to codeine toxicity, poor-metabolizer individuals will have an exaggerated response when the parent drug is more potent than its metabolites.  In addition, there are numerous drugs (not metabolized by CYP2D6) which interact to inhibit the function of CYP2D6 (eg. diphenhydramine).  Thus, these drugs can potentiate the effect of CYP2D6 on its substrates.

Other drugs commonly used by gastroenterologists and metabolized by CYP2D6 include tricyclic antidepressants, most SSRIs, metoclopropramide, ondansetron, and promethazine.  In ultra-metabolizer individuals, many of these drugs will not work because the quickly-produced metabolites, unlike the parent substrate, do not have therapeutic effects.

Additional references:

  • N Engl J Med 2004; 351: 2827-31.  Codeine Intoxication Associated with Ultrarapid CYP2D6 Metabolism. 62 year old: “12 hours after the last dose of codeine, the blood level of morphine was 20 to 80 times as high as the blood level that would have been expected on the basis of measurements in healthy persons ” due to ultrametabolism of CYP2D6 in combination with inhibition of CYP3A4 activity by other medications
  • CYP2D6 – Wikipedia, the free encyclopedia
  • Drug and Alcohol Dependence 89 (2007) 190–194. Association of CYP2D6 ultrarapid metabolizer genotype with deficient patient satisfaction regarding methadone maintenance treatment
  • What happens when codeine is used with drugs – WorstPills.org –

Case finding for hepatitis C

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A previous post noted the failure of risk-based screening for hepatitis C virus (HCV) (Unknown unknowns for Hepatitis C).  Because risk-based screening has not been effective, the CDC has proposed a different strategy, one time testing of all baby boomers:

http://www.cdc.gov/nchhstp/newsroom/HepTestingRecsPressRelease2012.html

“On the eve of the first ever National Hepatitis Testing Day (May 19), the Centers for Disease Control and Prevention is issuing draft guidelines proposing that all U.S. baby boomers get a one-time test for the hepatitis C virus. One in 30 baby boomers – the generation born from 1945 through 1965 – has been infected with hepatitis C, and most don’t know it.”

Breastfeeding: protection from asthma

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Good news for breastfed babies –breastfeeding may reduce risk of wheezing and asthma for several years (J Pediatr 2012; 160: 991-6).

In this prospective birth cohort study of 1105 infants from New Zealand, detailed feeding information was obtained at 3, 6, and 15 months which allowed calculation of breastfeeding duration. This information was correlated with information about wheezing and asthma collected at 2, 3, 4, 5, and 6 years.

Findings (after controlling for confounding variables):

  • Each month of exclusive breastfeeding was associated with significant reductions in asthma at all timepoints.  The effect was most prominent at younger ages.
  • The authors estimate that if every infant in the cohort had been exclusively breastfed for 6 months, that asthma would have been reduced by 50% at 2 years, 42% at 3 years, 30% at 4 years, 42% at 5 years, and 32% at 6 years.
  • In atopic children, the effects of exclusive breastfeeding are more pronounced.  In this study, exclusive breastfeeding for ≥3 months reduced asthma at ages 4, 5, and 6 by 62%, 55%, and 59% respectively.

The authors note that not all studies have found that breastfeeding improves asthma.  However, most of these studies reported outcomes in older children.

Related Posts:

Breastfed babies less likely to develop fatty liver

More evidence that breastfeeding improves cognitive development

Additional references:

  • -NEJM 2011; 364: 701, 769.  Living on a farm decreases risk of childhood asthma.
  • -Thorax 2009; 64: 604-9. Breastfeeding and asthma in children followed for 8 years.
  • -Br Med J 2007; 335: 815-20.  Longer time of breastfeeding does not reduce allergy/asthma. n=17,046 pairs of mother-infant (13,889 followed up at age 6.5yrs)

NAFLD Guidelines 2012

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Given the pervasiveness of Non-alcoholic Fatty Liver Disease (NAFLD), updated practice guidelines are worth a look (Hepatology 2012; 55: 2005-23, also in Gastroenterology 2012; 142: 1592-1609)).  While the review includes updated information on incidence, prevalence, risk groups, natural history, the focus remains on specific graded recommendations.

These AGA/AASLD/ACG guidelines do not recommend screening adults due to uncertainties surrounding diagnostic tests and treatment.  This includes high risk populations such as diabetics and bariatric patients.  In addition, unlike recent obesity guidelines from the AAP (Pediatrics 2007; 120: S164-192), these guidelines do not recommend screening children for NAFLD.

Specific management recommendations:

  • Exclude competing etiologies in patients with suspected NAFLD: iron studies, autoantibodies, Wilson’s, viral hepatitis, celiac serology, muscle disease
  • Consider liver biopsy in higher risk patients: metabolic syndrome patients, patients with higher NAFLD Fibrosis score, or before treatment
  • Serum/plasma CK18 is promising biomarker.  Not recommended for routine practice at this time.

Treatment Recommendations:

  • Weight loss (3-5%) helps steatosis and greater losses (up to 10%) may be needed to improve necroinflammation.
  • Metformin –not recommended for liver disease in NASH/NAFLD.
  • Pioglitazone can be used to treat steatohepatitis; however, “long-term safety and efficacy of pioglitazone in patients with NASH is not established.”
  • Vitamin E at 800 units/day improves liver histology in biopsy-proven NASH.  Not recommended without biopsy-confirmed NASH, in diabetic patients, or patients with cirrhosis.  Concern with Vitamin E in adults has been an association with increased all-cause mortality in some studies (but not in others).
  • Avoid alcohol in patients with NAFLD

Website to download PDF version:

http://www.gastro.org/journals-publications/news/societies-develop-new-nafld-clinical-practice-guideline

Another opinion on which patients to biopsy:

http://www.gastro.org/journals-publications/aga-perspectives/june-july-2012/should-we-routinely-do-liver-biopsy-in-nafld-patients

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