Category Archives: Uncategorized

Pulmonary Complications Associated with Chronic Liver Disease

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A useful review of “pulmonary complications in chronic liver disease” (Hepatology 2014; 59: 1627-37) has been published.

The main topics included hepatopulmonary syndrome (HPS) , portopulmonary hypertension (POPH), and hepatic hydrothorax (HH).

A few of the key points:

HPS is most common of these conditions and is identified in 5-30% of cirrhosis patients.  It is identified with abnormal oxygenation (screening with pulse ox <96%) due to intrapulmonary vascular dilatations. There is no established medical therapy.  It is reversible with liver transplantation.

The hallmark of POPH is the development of pulmonary arterial hypertension associated with portal hypertension.  It occurs in 5-10% of cirrhosis patients and often presents as dyspnea on exertion/fatigue.  There are numerous pharmacologic treatments that may be useful, include the following:

  • prostacyclin analogs like epoprostenol
  • endothelin receptor antagonists like boesentan
  • phosphodiesterase-5 inhibitors like sildenafil, vardenafil, and tadalafil

Severe POPH is a relative contraindication for liver transplantation.

HH is a transudative pleural effusion seen in 5-10% of cirrhosis patients. Initial management includes salt restriction and diuretics.  Transjugular intrahepatic portosystemic shunt and thoracentesis are second-line options.  Liver transplantation is curative.

Related blog entries:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

 

 

The Search for a Dietary Culprit in IBD

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Uniformly, patients diagnosed with inflammatory bowel disease (IBD), both ulcerative colitis and Crohn disease, are interested in whether there is a dietary culprit which triggered their IBD and what modifications in their diet can help improve their IBD.  A really good summary of what we know has been published (Inflamm Bowel Dis 2014; 20: 732-41).

A summary of the key points:

Traditional dietary recommendations:  These diets may help decrease symptoms but are not thought to improve disease control.

  • Low-residue: <10-15 g/d of fiver. Potential deficiencies: folate, vitamin A, vitamin C, and potassium.  Overall, this diet is poorly studied.  “One small randomized controlled trial showed that low-residue diet made no difference in symptoms, need for hospitalization, need for surgery…when compared with an unrestricted diet.”
  • Lactose-free: potential deficiencies: calcium, vitamin D

Carbohydrate-restrictive:  Potential deficiencies with all carbohydrate restriction: folate, thiamine, vitamin B6

  • Specific carbodydrate diet: allows only monosaccharides.  Restricts complex sugars, starches, grains and legumes.  This diet was popularized by Elaine Gottschall in 1994 (Breaking the Vicious Cycle) but was developed by Dr. Sidney Haas in 1924.  The premise of SCD is that “complex carbohydrates and legumes are poorly absorbed in gastrointestinal disease…they promote bacterial overgrowth and fermentation.  By-products from bacterial dysbiossis are postulated to contribute to gut inflammation.”  Nevertheless, it “has been poorly studied.”
  • Low FODMAPs (see numerous previous posts).  “A small restrospective study…showed that the low FODMAPs diet resulted in improvement in functional symptoms present in patients with IBD who were in remission.”  This diet is difficult for long-term adherence.
  • Gluten-free: not truly a carbohydrate-restrictive diet, but breads/cereals contain large amounts of carbs. “No evidence that a gluten-free diet has any effect on disease activity in IBD.”

Fat-modified diets

  • Fat-restrictive diets: “On a cellular level, multiple animal studies have shown that prolonged feeding of a high-fat diet seems to promote colitis/ileitis and to perturb barrier function…shifts in microbiome composition…Despite some biologic plausibility, there is a paucity of data evaluating efficacy of fat-restrictive diet for IBD management.”
  • Vegetarian/semi-vegetarian: Potential deficiencies: iron, vitamin B12 (vegans), calcium, vitamin D, ω-3 fatty acids.   A small study of 22 patients with Crohn’s disease who adhered to a semi-vegetarian diet, had lower rate of relapse.  “There does not seem to be sufficient evidence at this time to recommend eliminating meat to patients with IBD as a means to control their disease.”
  • Modified ratio of ω-3/ω-6 polyunsaturated fat: “The efficacy of dietary interventions with ω-3 PUFA has been disappointing..recently, 2 large multicenter clinical trials demonstrated that ω-3 PUFA (fish oil) at a dose of 4 g/day was not significantly better than placebo at maintaining remission in CD.”

Restriction of Multiple food groups

  • Paleolithic: based on the “premise that human genetics have scarcely changed over the past 3000 years, and thus modern humans are genetically adapted to the diet of their Paleolithic ancestors (i.e. Stone Age)…daily calories should come from plant sources (50-65%) and from animal sources (35-45%) with fish preferred over meat.  Most of the restricted foods are carbohydrates..refined salt, and refined oils as well as any “processed foods.”  However, there are “no data that this diet has any effect in IBD.”  Previous reports of improvement in IBD are mainly testimonials (anecdotal evidence).
  • Exclusive enteral nutrition (EEN)/Elemental/Semielemental: In pediatric CD, “EEN has been shown to be as effective as corticosteroids in inducing remission (70-90%)..EEN does not seem to be effective in UC.”  High rate of relapse when diet is stopped.  Formula type does not seem to be very important.

Take-home message: “Clinical trials in all dietary strategies (with possible exception of EEN in pediatric patients) are lacking and further study is needed.” “From the current evidence available, a low FODMAPS or gluten-free diet may be the most helpful in controlling diarrheal and bloating symptoms…However, …symptom improvement does not equate to remission or objective evidence of disease regression.”

Related Blog Posts:

ImproveCareNow has published information on IBD and Nutrition as well.  Here’s an excerpt from their Circle eNewsletter:(initially published April 2013, Stacie Townsend, MS, RD, LDN, CSP)

Diet is an important part of your IBD treatment plan and should be used in conjunction with medications. Proper nutrition plays a critical role in managing IBD. Eating healthfully and in appropriate amounts will improve IBD symptoms, contribute to age-appropriate growth, and decrease risk of anemia, poor bone density, and vitamin/mineral deficiencies. It can also increase effectiveness of IBD medications.

No one diet has been proven to prevent IBD or to prevent flare ups, although several diet books and plans have claimed to “cure IBD”. Unfortunately, there is little scientific evidence to prove that these diet plans, such as the Specific Carbohydrate Diet (still being studied) and the Guts and Glory Program, are effective, and most of these plans avoid entire food groups, which can then lead to vitamin and mineral deficiencies and poor weight gain.

Nutritionists frequently get asked what foods are safe for people with IBD, and creating a diet plan for you is often trial and error… The best diet plan is one that includes all food groups (proteins, grains, fruits, vegetables, dairy, and oils) and in appropriate portions for your age, weight, and physical activity level… If gas, bloating, and diarrhea are among your symptoms, lactose free dairy products may be better tolerated.

So what IS the most appropriate diet for IBD? The United States Department of Agriculture’s food guidance system, MyPlate, is the appropriate diet plan for you… and the SuperTracker within the MyPlate website can help you track what you eat each day, and how your diet measures up to the recommended diet plan for you.

General nutrition guidelines for individuals with IBD include:

  • choose foods from all food groups
  • limit fried/fatty foods, caffeine and spicy foods, especially if these foods worsen symptoms of IBD
  • drink fluids at each meal to maintain hydration
  • consume a multivitamin daily to aid nutrient absorption
  • consume small frequent meals (eat every 2-3 hours while awake) if volume of foods at a meal is an issue

…If you want additional help with your diet, make an appointment to see our nutritionist.

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

 

Shwachman-Diamond Syndrome

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A recent study provides an update on the variable clinical presentation of Shwachman-Diamond syndrome (SDS) (J Pediatr 2014; 163: 866-70).

SDS, an autosomal recessive disorder, is characterized by exocrine pancreatic dysfunction, bone marrow dysfunction, and predisposition to myelodysplasia/leukemia.  It is due to a mutation in the SBDS gene located on chromosome 7q11 (found in ~90% of classically presenting cases of SDS.

Using a North American Registry, the authors reviewed the records of 37 patients (all who have had mutations in SBDS gene). Key findings:

  • Neutropenia was evident at presentation in 30/37 (81%)
  • Only 51% had both neutropenia and steatorrhea at presentation
  • 24/37 (65%) had congenital anomalies: 3 with ventricular septal defects, 1 malrotation, 1 imperforate anus, 9 thoracic dystrophy (rib abnormalities), 2 with short arms/legs, 4 with metaphyseal dysplasia, 1 with Chiari malformation (type 1), 2 with testicular atrophy.
  • Medical comorbidities included elevated LFTs in 15, adrenal insufficiency in 1, hypopituitarism in 1, type 1 diabetes in 1, hypothyroid in 1, and eczema in 11.

Take-home message: Normal pancreatic imaging studies and normal fecal elastase do not rule out SDS. In addition, frequently there are associated anomalies and comorbidities.

Will Lubiprostone Help Children with Functional Constipation?

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A recent open-label study of lubiprostone examined its use in children younger than 18 years (2007-2008) at 22 U.S. centers (JPGN 2014; 58: 283-91).

Lubiprostone (Amitiza) activates chloride-channel protein-2 in the gastrointestinal epithelium and promotes secretion of chloride ions and fluid.  This results in more frequent bowel movements (BMs) and improved motility.  To determine its safety and effectiveness in the pediatric population, the investigators enrolled 127 patients (124 were treated and analyzed and 109 completed the 4-week study).  After a 2-week observation period, several doses of lubiprostone were compared: 12 μg QD, 12 μg BID, 24 μg BID.  There was no placebo group.  The mean age of the participants was 10.2 years.

Results:

  • Mean spontaneous BM frequency increased from baseline: 3.1/week versus 1.5/week.  Overall, at each week in treatment ≥ 43% achieved ≥ 3 spontaneous BMs/week.
  • 62% experienced a spontaneous BM within 48 hours of starting treatment.
  • Common adverse reactions: Nausea (18.5%), vomiting (12.1%), diarrhea (8.1%), abdominal pain (7.3%) and headache (5.6%). Overall, 65% of patients experienced ≥ 1 adverse effect and this was highest (78%) in the subset of patients receiving the highest dosage

Bottomline: Current guidelines recommend osmotic agents like polyethylene glycol (PEG) (Miralax) as first-line treatment.  This short-term study shows lubiprostone may be an alternative in nonresponders, though more data on long-term outcomes are needed.

Related blog posts:

Is There a Link Between Maternal Iron Supplementation and Celiac Disease?

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According to a recent study, maternal iron supplementation may increase the risk of celiac disease in children (Clin Gastroenterol Hepatol 2014; 12: 624-31).

Using the Norwegian Mother and Child cohort study (1999-2008) which included data for 78,846 children, the authors analyzed the risk of developing celiac disease by examining prospectively collected questionnaires regarding iron supplements, diet, and anemia.  Questionnaires were obtained 3 times during pregnancy, then at age 18 months, 6 years, 7 years and 8 years.

Key Results:

  • 4.65 of 1000 children whose mothers took iron supplements while pregnant developed celiac disease compared to 3.15 of 1000 whose mothers did not.
  • After adjustment for multiple variables, the OR was 1.33 for children developing celiac disease if their mother took iron supplementation during pregnancy.
  • The authors note that maternal anemia was not associated with celiac disease in offspring nor was iron supplementation in childhood.

While these findings are intriguing, the associated editorial (pg 632-35) notes that unmeasured confounding variables could explain the findings.  For example, undiagnosed maternal celiac disease which could increase the likelihood of iron exposure could increase the risk of celiac disease in the offspring and account for the increased association with iron supplementation.

Take-home message (from the editorial): “it is premature to argue that iron supplementation during pregnancy should be avoided in individuals with celiac disease…the observed effect (an absolute risk increase of 0.15%) is modest in magnitude. This exposure is not driving the slow, ongoing epidemic of celiac disease.”

Related blog links:

Head-to-Head: Capsule Endoscopy versus Colonoscopy

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A recent study shows how useful capsule endoscopy (CE) can be in diagnosing Crohn disease (Clin Gastroenterol Hepatol 2014; 12: 609-15).  Congratulations to one of my partners, Dr. Stan Cohen, who is one of the authors.

This prospective study examined 80 patients with signs and/or symptoms of small-bowel Crohn disease (age, 10-65 years) who underwent CE, small-bowel follow-through (SBFT), and colonoscopy.

Presenting suggestive features included the following:

  • Diarrhea >6 weeks but less than 3 years
  • Abdominal pain >6 weeks but less than 3 years
  • Extraintestinal IBD manifestations: pyoderma gangrenosum, erythema nodosum, perianal disease, arthritis, aphthous stomatitis, and uveitis
  • Along with abnormal laboratory/clinical finding:
  1. positive inflammatory marker: sedimentation rate, C-reactive protein, calprotectin/lactoferrin
  2. unexplained iron deficiency
  3. hypoalbuminemia
  4. positive IBD serology (eg. anti-Saccharomyces cerevisiae antibodies)
  5. or other clinical findings: recurrent fevers, GI bleeding, growth failure, abnormal radiologic study

Results:

  • CE/colonoscopy in combination detected 107 of 110 inflammatory lesions (97.3%)
  • SBFT/colonoscopy detected 63 lesions (57.3%)
  • “The diagnostic yield of CE compared with colonoscopy was not different.”
  • Of the 80 patients with suspected Crohn disease, 25 (31.3%) had the diagnosis confirmed. 9 patients had diagnostic findings on at least 2 of the 3 modalities.  11 were diagnosed with CE alone and 5 by colonoscopy alone.

The authors conclude that colonoscopy remains the initial diagnostic test of choice.  However, “CE is safe and can establish the diagnosis of Crohn’s disease in patients when ileocolonoscopy results are negative or the terminal ileum cannot be evaluated.”

Take-home message: in patients with symptoms suggestive of Crohn disease, a negative colonoscopy is not sufficient to exclude the disease.  Other modalities like CE or MRE may be needed.

Related post:

Pediatric Capsule Endoscopy Experience

Macrolide Antibiotics and Pyloric Stenosis

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It is well-recognized that infants who receive macrolide antibiotics are at increased risk of pyloric stenosis. A recent study (BMJ 2014;348:g1908) indicates that maternal macrolide intake can also increase the risk of pyloric stenosis in their infants.

Link to article from NASPGHAN twitter feed: http://t.co/CnkbdZoRVf

Conclusions Treatment of young infants with macrolide antibiotics was strongly associated with IHPS and should therefore only be administered if potential treatment benefits outweigh the risk. Maternal use of macrolides during the first two weeks after birth was also associated with an increased risk of IHPS. A possible association was also found with use during late pregnancy.

EXTEND & MUSIC: Optimizing Crohn Disease Care

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As noted in recent posts (see links below), there is increased interest in showing direct mucosal healing and achieving optimal drug levels in controlling Crohn disease (CD).

  1. Clin Gastroenterol Hepatol 2014: 12: 414-422.
  2. Clin Gastroenterol Hepatol 2014: 12: 423-431.

The first study examines the rates of deep remission induced by adalimumab.  Deep remission is “defined as the absence of mucosal ulceration and CD Activity Index scores less than 150.”

Design: The data is derived from the EXTEND (EXTend the Safety and Efficacy of Adalimumab Through ENDoscopic Healing) trial.  EXTEND was a 52-week randomized, double-blind, placebo-controlled trial of adalimumab (ADA) for adults (n=135) with moderate to severe ileocolonic CD.  All patients received open-label induction with ADA (160/80 mg at weeks 0/2), then were randomized to ongoing ADA 40 mg every other week or placebo.

Results: Rates of DR were 16% in ADA patients compared with 10% of placebo-treated patients at week 12.  By week 52, 19% of ADA patients were in DR compared with 0% of placebo-treated patients.

Key findings:

  • Analysis showed that shorter disease duration was associated with DR.  One-third of patients with CD for <2 years achieved DR.
  • Patients with DR had better outcomes than those with only mucosal healing (n=8); those with isolated clinical remission (n=19, no mucosal healing), but not DR, had similar outcomes to those with DR.  The associated editorial (pg 432) notes “symptoms will still make patients go to the emergency department, or miss work, or feel miserable, regardless of how good their mucosa looks.”
  • The authors state that during the 40 weeks after early CR, “estimated savings were $6117 for direct medical costs and $4243 for indirect costs” (total $10,360).  This monetary savings may not be offset in clinical practice by ileocolonoscopy which is not only invasive but also expensive.

Conclusion (from the authors): “Before any recommendation to adopt DR as a treatment target, establishing a clear association between achievement of DR and better long-term prognosis is necessary.”  The editorial advises against adopting DR as a treatment goal: “combining symptoms and mucosal healing into 1 end-point should be reconsidered as a measure of response to anti-inflammatory therapies.”

The second study, referenced above, examined plasma concentrations of certolizumab pegol (CZP) and endoscopic outcomes of patients with Crohn disease.

Design: The authors analyzed data (post hoc analysis) from the MUSIC (The Endoscopic MUcoSal Improvement in Patients with Active CD Treated with CZP) study. Adult patients received subcutaneous CZP (400 mg) at weeks 0, 2, and 4 followed by every 4 week treatment for 52 weeks.  Endoscopic evaluation took place at weeks 0, 10, and 54 and CZP concentrations were measured at weeks 8 and 54. At week 10, there were 45 patients analyzed and at week 54, 18 patients.

Key findings:

  • Mean CZP concentrations: 11.1 mcg/mL at week 8 (4 weeks after previous dosing) and 14.9 mcg/mL at week 54 (2 weeks after previous dosing).
  • Higher CZP concentration (by quartile values) correlated with endoscopic response (P=.0016) and remission (P=.0302) at week 10.
  • Among those with the highest CZP values, their 8-week CDEIS (CD Endoscopic Index of Severity) remission rate was 75% (12/16).  Overall, CDEIS remission was noted in 56% (25/45) at week 8.
  • At week 54, endoscopic remission correlated with plasma CZP values (P=.0206).
  • Both high CRP and high body weight inversely correlated with CZP concentrations.

Conclusion from this study: As with other anti-TNF agents, higher serum levels were associated with mucosal healing.  However, the data do not prove causality.  “It is possible that higher trough concentrations at week 8 may be a consequence of mucosal healing” rather than the reverse.

Bottomline: These two studies together show that achieving optimal long-term response correlates with therapeutic drug levels and mucosal healing.  At the same time, these studies along with many other indicate that we have along way to go in order for us to achieve these objectives consistently.

Related blog posts:

 

Camp Weekaneatit for Kids with Celiac

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From my colleague, Jeff Lewis:  “The camp is called Camp Weekaneatit, it is July 13 to July 18, overnight camp, strictly gluten-free so the kids can eat what they want without having to worry.  Its part of Camp Twin Lakes – an organization that hosts tons of medical camps.  We have kids from all over – as far away as California the last two years.  Scholarships are available.”

Anyone who tries to follow a strict gluten-free diet knows how difficult it can be to take a trip outside the home.  This camp lets kids enjoy camp without the worry about the next meal or snack.  Spread the word!

 

CampInformation 

Are you familiar with CMMR-D?

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In a recent review, CMMR-D and Lynch syndrome are reviewed (JPGN 2014; 58: 144-52). The term CMMR-D refers to constitutional mismatch repair deficiency.  This occurs when an individual inherits two MMR gene defects (rather than one gene defect in Lynch syndrome). CMMR-D can occur when a different mutation is inherited from each parent. MMR genes include MLH1, MSH2, MSH6 and PMS2.

Unlike Lynch syndrome when screening for colorectal cancer (CRC) usually starts at age 20 years or 5 years before first CRC in family, with CMMR-D screening recommendations include yearly endoscopic evaluation beginning at age 3 years or at diagnosis.  Complete management guidelines are listed in Table 4.