Real-World = Partially-Treated Celiac Disease

A recent prospective observational study reinforces the idea that most people with celiac disease are unable to accomplish a strict gluten-free diet (GFD): JP Stefanolo et al. Clin Gastroenterol Hepatol 2021; 19: 484-491. Real-World Gluten Exposure in Patients With Celiac Disease on Gluten-Free Diets, Determined From Gliadin Immunogenic Peptides in Urine and Fecal Samples

The investigators enrolled 53 adults with celiac disease (CD) for at least two years and followed symptoms as well as stool/urine testing for gluten immunogenic peptide (GIP). “GIP in stool can detect gluten consumption of more than 40 mg/d and the urine tests are positive from 40 and 500 mg/d of gluten.”

Key findings:

  • Over the 4-week study period, weekend samples (urine) identified 70% of patients excreted GIP at least once, compared with 62% during weekdays (stool).
  • Patients had a median of 3 exposures during the 4 weeks.
  • Also, the authors noted increases in GIP excretion towards the end of the study. “This suggests a potential Hawthorne effect that could be explained by a decrease in hypervigilance that often is seen in a context of research studies.”

The authors note that GIP “excretions of greater than 2 mcg/g in stool or greater than 12 ng/mL in urine can induce mucosal damage in almost 100% of patients.”

My take: This study adds to the body of literature emphasizing the high rate of inadvertent gluten exposure.

Related blog posts:

Before and After at Lake Michigan shoreline (1 month apart in Evanston, IL)

Early January -Evanston, IL
Early February -Evanston, IL

AAP Bariatric Surgery Recommendations

A recent policy statement (SC Armstrong et al. Pediatrics 2019; 144 (6): e20193223) outlines current evidence regarding adolescent bariatric surgery and makes recommendations for practitioners & policymakers.  There is also an accompanying technical report which provides more detail and supporting evidence.  Thanks to Ben Gold for this reference.

Full PDF Link: Pediatric Metabolic and Bariatric Surgery: Evidence, Barriers, and Best Practices

This policy statement uses “adolescent” to refer to a person from age 13 years to age 18 years.

Background: “Although nearly 4.5 million US adolescents have severe obesity, current estimates suggest that only a small faction undergo metabolic and bariatric surgery…Many providers prefer a “watchful waiting” approach, or long-term lifestyle management.50 However, current evidence suggests that pediatric patients with severe obesity are unlikely to achieve a clinically significant and sustained weight reduction in lifestyle-based weight management programs53 and that watchful waiting may lead to higher BMI and more comorbid conditions…In addition, comparative data examining
postoperative outcomes along the severely obese BMI spectrum (low, middle, and high) suggest that adolescents within a lower BMI range (BMI <55) at the time of bariatric
surgery have a higher probability of achieving nonobese status when compared with individuals with a higher starting BMI (BMI ≥55).”

From Table 2 -Indications for Bariatric Surgery:

  1. Class 2 obesity, BMI ≥35, or 120% of the 95th percentile for age and sex, whichever is lower  along with clinically significant disease, including obstructive sleep apnea (AHI .5), T2DM, IIH, NASH, Blount disease, SCFE, GERD, and hypertension
  2. Class 3 obesity, BMI ≥40, or 140% of the 95th percentile for age and sex, whichever is lower. Clinically significant disease is not required but commonly present

Recommendations for practitioners:

  • Seek high-quality multidisciplinary centers that are experienced in assessing risks and benefits of various treatments for youth with severe obesity, including bariatric surgery, and provide referrals to where such programs are available.
  • Identify pediatric patients with severe obesity who meet criteria for surgery and provide
    timely referrals to comprehensive, multidisciplinary, pediatric-focused metabolic and bariatric surgery programs.
  • Monitor patients postoperatively for micronutrient deficiencies and consider providing iron, folate, and vitamin B12 supplementation as needed.
  • Monitor patients postoperatively for risk-taking behavior and mental health problems.

SYSTEM-LEVEL RECOMMENDATIONS:

  • Advocate for increased access for pediatric patients of all racial, ethnic, and socioeconomic backgrounds to multidisciplinary programs
  • Consider best practice guidelines, including avoidance of unsubstantiated lower age limits, in the context of potential health care benefits and individualized patient-centered care.
  • For insurers: Provide payment for care (pre-operative, operative & post-operative). Reduce barriers to pediatric metabolic and bariatric surgery (including inadequate payment, limited access, unsubstantiated exclusion criteria, and bureaucratic
    delays in approval requiring unnecessary and often numerous appeals) for patients who meet careful selection criteria.

My take: These recommendations are in general agreement with previous guidelines.  I think having the stamp of approval from the AAP is likely to help in getting coverage and may shift attitudes.

Related blog posts:

FDA Approval of HCV Medications for Children, 12-17 years

4/7/17:  FDA Okays Two Hepatitis C Drugs for Our Pediatric Patients

An excerpt:

The US Food and Drug Administration (FDA) today granted approval for supplemental applications for sofosbuvir (Sovaldi) and ledipasvir and sofosbuvir (Harvoni) to treat hepatitis C virus (HCV) in children ages 12 to 17…

Sovaldi, combined with ribavirin, is indicated to treat pediatric patients 12 years older or weighing at least 77 pounds (35 kilograms) with genotype 2 or 3 HCV infection without cirrhosis or with mild cirrhosis.   Harvoni is indicated for the treatment of pediatric patients 12 years and older or weighing at least 77 pounds (35 kilograms) with HCV genotype 1, 4, 5 or 6 infection without cirrhosis (liver disease) or with mild cirrhosis.   The approval for the new indication was based on an open-label, multicenter clinical trial including 100 pediatric patients 12 years and older looking at the safety, pharmacokinetics, and efficacy of Harvoni to treat HCV genotype 1 infection…

health care professionals should screen all patients for evidence of current or prior HBV infection before starting treatment with Harvoni or Sovaldi.

Reaching Consensus on Bariatric Intervention in Children and Adolescents

A recent medical position paper (Nobili V, et al. JPGN 2015; 60: 550-61) provides guidance for bariatric surgery intervention in children and adolescents with and without nonalcoholic fatty liver disease (NAFLD).

While the authors acknowledge that bariatric surgery can “dramatically reduce the risk of adulthood obesity and obesity-related diseases,” they advocate its use in adolescents with the following:

  • BMI >40 kg/m-squared with severe comorbidities: type 2 diabetes mellitus, moderate-to-severe sleep apnea, pseudotumor cerebri, or NASH with advanced fibrosis (ISHAK score >1)
  • BMI >50 kg/m-squared with mild comorbidities: hypertension, dyslipidemia, psychological distress, gastroesophageal reflux, anthropathies, NASH, impairment in activities of daily living, mild obstructive sleep apnea, panniculitis, chronic venous insufficiency, urinary incontinence
  • Additional criteria: have attained 95% of adult stature, failed behavioral/medical treatments, psychological evaluation perioperatively, avoid pregnancy for 1 year after surgery, will adhere to nutritional guidelines after surgery, informed assent from teenager (along with parental consent)

Key points:

  • “There is a lack of randomized controlled trials examining the effects of bariatric surgery on NAFLD or NASH.”  In Table 3, the authors provide a summary of 16 previous studies/outcomes; though none of the studies enrolled more than 60 patients.
  • In an adult prospective study with 381 patients (Mathurin P et al. Gastroenterol 2009; 137: 532-40), there was a significant decline in the severity/prevalence of steatosis and resolution of NASH at 1 and 5 years.
  • Bariatric surgery, in adult studies, have improved diabetes, insulin resistance, hypertension, and dyslipidemia.
  • Patients who have “undergone bariatric surgery show higher suicide rates than the general population.”  Psychological evaluation should be integrated with surgical decision.
  • Type of surgery: Roux-en-Y Gastric Bypass (RYGB) is favored by the authors; they also discuss studies with Laparoscopic Adjustable Gastric Banding (LAGB).  “RYGB and LAGB are the 2 main surgical procedures that have been used in pediatric obesity.  RYGB is considered a safe and effective option for adolescents with extreme obesity, as long as appropriate long-term follow-up is provided. LAGB has not been approved by Food and Drug Administration for use in adolescents, and there should be considered investigational only.”

It is interesting that the authors are so deferential to the Food and Drug Administration.  It is clear from their position paper that LAGB has similar evidence supporting its use in adolescents as RYGB.  They even note that it has potential for reversibility and “an excellent safety profile with a lower risk of postoperative vitamin deficiencies when compared with biliopancreatic diversion and RYGB.”

Bottomline: Given the continuation of the obesity epidemic, additional pediatric medical expertise will be needed to help evaluate adolescents for bariatric surgery and to follow them postoperatively.

Related blog posts: