Online Aspen Webinar (Part 6) -NAFLD and NASH

Aspen Online Webinar July  14-16, 2020

Below I’ve included some of my notes and slides.  There may be errors of omission or transcription.

What’s Hot? NAFLD and NASH Stavra Xanthakos

  • Fatty liver disease burden of NAFLD and NASH is increasing.  This increases the rate of cirrhosis, liver cancer and liver transplantation; the latter is being needed at younger ages
  • Explained that “Lean” (normal BMI) NAFLD is common
  • Diabetes is strongest risk factor for severe fatty liver disease (NASH or fibrosis). PNPLA3 is genetic risk factor for NAFLD risk.
  • Discussed treatment, particularly diet  and bariatric surgery.  Stated that some emerging treatments look promising.
  • In those with suspected NAFLD, Dr. Xanthokos recommends liver biopsy, if lifestyle therapy is ineffective, under specific circumstances: prior to bariatric surgery, in some cases to determine severity, and prior to instituting therapy (eg Vitamin E)

              

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Probiotics in Preemies: Lifesaving Therapy

Lots of studies have indicated that probiotics may be beneficial in premature newborns; the problem is that there are currently no FDA-approved probiotics for preterm infants. The use of probiotics as a non-regulated FDA product leads to the potential risk of contamination due to inconsistent quality control as well as variability in the strains and concentrations.  The risks are not inconsequential as there has been a report of 29-week infant who died from mucormycosis due to probiotic contamination with mold.

Despite the potential problems with probiotics in this population, their usage is increasing as described in a recent multicenter retrospective cohort study (KD Gray et al. J Pediatr 2020; 222: 59-64) which took place between 1997-2016 with 78,076 infants (23-29 weeks gestational age) in 289 NICUs.

Key findings

  • 3626 (4.6%) received probiotics
  • Probiotic use increased over the study period (>10% in 2015 & 2016)
  • By matching 2178 infants who received probiotics with 33,807 without probiotics, the authors determined that those received probiotics had a decrease likelihood of necrotizing enterocolitis (OR 0.62) and death (OR 0.52).  The authors observed an increase in Candida infection (OR 2.23); though, this is an infrequent infection and the absolute difference in risk was <1%
  • Limitations: “similar to many previous studies, there was great variation in probiotic products and organisms, as well as a lack of dosing information, which made it unclear which product, organism, or dose might be most effective.”  Also, other contributing factors like consumption of breastmilk and antibiotic exposure are not detailed in this report.

My take: Probiotics could be life-saving for premature infants. It would be nice if we could find out which strains work and which ones do not as well as to assure safe manufacturing processes.

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ACG Review (Zobair Younassi, MD): NAFLD and NASH

For PDF copy of slides: NAFLD and NASH

Dr. Zobair Younassi gave a recent virtual grand rounds –here are some of the slides:

Epidemiology:

Natural History:

  • Progression of disease is not linear
  • Fatty liver disease is a multisystem disorder.  Cardiovascular disease is leading cause of death in patients with fatty liver disease
  • Fatigue (~50%) is common with fatty liver disease

Main treatment:

  • Weight loss -Mediterranean diet may be helpful
  • Exercise
  • No FDA-approved treatments, though pioglitizone supported by AASLD for biopsy-proven NASH
  • Public health interventions are needed

Short Gut Diet -CHOA Approach

Recently Kipp Ellsworth, with input from members of the nutritional team, developed our first institutional Short Gut Diet.

Per Kipp, this diet is “designed to facilitate digestion while minimizing abdominal pain and ostomy/stool output in our inpatients with truncated intestinal anatomy.  Previously, clinicians ordered a regular diet for our short gut patients, with parents and nurses providing oversight of the ordering process based on their knowledge of short gut diet precepts.  Obviously this non-standardized approach resulted in significant noncompliance, another onerous daily task for nursing, and a failure of inpatient short gut diet principles reinforcement.  I anticipate the new diet serving as an omnipresent education tool, reinforcing short gut diet precepts for patients and parents during their inpatient stays.”

Related blog posts:

Nutritional Risks in Adolescents After Bariatric Surgery; Prevention of Childhood Obesity; Convalescent Serum for COVID-19

S Xanthakos et al. Clin Gastroenterol Hepatol 2020; 18: 1070-81. Full Text: Nutritional Risks in Adolescents After Bariatric Surgery

This was a multicenter prospective cohort study with 226 adolescents (mean age 16.5 years, mean BMI of 52.7) who had either Roux-en-Y bypass (RYGB, n=161) or vertical sleeve gastrectomy (VSG, n=67).

Key findings:

  • At 5 years, 59% of RYGB and 27% of VSG had ≥2 nutritional deficiencies
  • The most prevalent abnormality we observed was hypoferritinemia, which affected nearly twice as many RYGB recipients by Year 5 compared with VSG.
  • Vitamin B12 status likewise worsened disproportionately after RYGB, despite similar trajectories of weight loss after VSG
  • Image below shows the prevalence of abnormal values for vitamins over time

My take: This study shows that adolescents undergoing VSG had fewer nutritional deficiencies than RYGB and provides data supporting nutritional monitoring after bariatric surgery.

B Koletzko et al. JPGN 2020 70: 702-10. Full Text: Prevention of Childhood Obesity: A Position Paper of the Global Federation of International Societies of Paediatric Gastroenterology, Hepatology, and Nutrition (FISPGHAN)

Related blog posts (Bariatric Surgery):

Related blog posts (Obesity):

 

Not Curing Obesity with Fecal Microbiota Transplantation & More on Remdesivir

A recent pilot (n=22) double-blind study (JR Allegrett et al. Clin Gastroenterol Hepatol 2020; 18: 855-63) pours cold water on the idea that repopulating one’s microbiome would be helpful in treating obesity.

In this study, the authors examined obese patients without diabetes, nonalcoholic steatohepatitis, or metabolic syndrome.  In the treatment group, patients received FMT by capsules: 30 capsules at week 4 and then a maintenance dose of 12 capsules at week 8.  All FMT was derived from a single lean donor.

Key findings:

  • There were no significant changes in mean BMI at week 12 in either group.
  • Patients in the FMT group had sustained shifts in microbiomes associated with obesity toward those of the donor (P<.001).  In addition, bile acid profiles became more similar to the donor.

My take: Though this was a small study, it suggests that changing the microbiome by itself is likely insufficient to result in significant weight loss.

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JH Beigel et al. NEJM DOI: 10.1056/NEJMoa2007764 (May 22, 2020): Full text: Remdesivir for the Treatment of Covid-19 — Preliminary Report

This was a a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement (n=1063).

Key findings:

  • Faster recovery for remdesivir recipients: 11 days vs 15 days
  • Lower mortality rate: 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70, 95% CI, 0.47 to 1.04) (mortality difference did not reach statistical significance)

 

 

Celiac Studies -Increasing Prevalence (Italy) and Nonadherence Risks

S Gatti et al. Clin Gastroenterol Hepatol 2020; 18: 596-603.   The authors screened 4570 children (5-11 year olds) from 2015-16; this study included 80% of eligible children from two metropolitan areas in Italy.

Key findings:

  • 77 cases of children met diagnostic criteria for celiac disease (54 met criteria and 23 prior known cases)
  • Prevalence in this population, overall, was 1.58% (2015-16); in 1993-95, the adjusted prevalence was 0.88%
  • Celiac disease autoimmunity was noted in 96 .
  • 1960 (43%) had celiac disease associated haplotypes

A Myleus et al. Clin Gastroenterol Hepatol 2020; 18: 562-73.  In this systematic review, 49 studies (out of initial 703) were included in final analysis to determine risk factors and outcomes with nonadherence to treatment with gluten free diet.

Key findings:

  • Large range of adherence rates: 23% to 98% (median rates were 75-87%).
  • Adolescents were at increased risk of non-adherence
  • Children whose parents had good knowledge had higher adherence rates
  • There was not improved adherence over time, despite improvement in palatable gluten-free foods.

One of the other findings in the study was the lack of consensus about what defines strict adherence and how to measure it.

My take: The first study is in agreement with many others which have demonstrated higher prevalence of celiac disease now compared to previously.  The second study shows that adherence with treatment is highly variable and difficult to measure.

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Screenshot (797)

UNC Campus Pic (Chapel Hill)

Using Spot Urine Sodiums

A recent study (AKN Pedersen et al. JPEN https://doi.org/10.1002/jpen.1593) shows the utility of obtaining urine spot sodiums in patients with an ileostomy. Thanks to Kipp Ellsworth for sharing this reference.

Full link: A Single Urine Sodium Measurement May Validly Estimate 24‐hour Urine Sodium Excretion in Patients With an Ileostomy

Background: Sodium deficiency in patients with an ileostomy is associated with chronic dehydration and may be difficult to detect. We aimed to investigate if the sodium concentration in a single spot urine sample may be used as a proxy for 24‐hour urine sodium excretion.

Design: In this prospective, observational study, we included 16 adult individuals: 8 stable patients with an ileostomy and 8 healthy volunteers with intact intestines

Key finding:

  • There was a high and statistically significant correlation between 24‐hour natriuresis and urine sodium concentrations in both morning spot samples (n = 8, Spearman’s rho [ρ] = 0.78, P = 0.03) and midday spot samples (n = 8, ρ = 0.82, P = 0.02) in the patients with an ileostomy.

My take: In patients with ileostomy (and also short bowel syndrome), periodic urine sodium values (from morning or mid-day) will help detect subclinical sodium depletion.

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Atlanta Botanical Gardens

FMT Warning & “Get Your Butt in Gear” –Less Than 10% of Kids Meeting Guidelines for Healthy Movement

To lessen obesity, three health risk behaviors have been targeted:

  • Sedentary behavior -goal is to limit to 2 hours of screen time in 24 hours
  • Physical activity -goal is 1 hour (or more) of moderate to vigorous activity
  • Sleep duration -goal is 9-12 hours (ages 6-12 years) and 8-10 hours (13-18 years)

A recent study (X Zhu et al. J Pediatr 2020; 218: 204-9) shows that <10% of U.S. kids meet these goals.  The authors examined data (2016-17) from the National Survey of Children’s Health (NSCH) dataset (n=71,811)

Key findings:

  • 80.9% did NOT meet physical activity goal
  • 76.2% did meet screen time goal
  • 581% did meet sleep goal
  • However, only 9.4% met all 3 goals
  • Not meeting these ‘movement’ guidelines was associated with obesity, particularly in females (aOR 4.97 compared to aOR 3.99 for males)

My take: We are all made to be different shapes and sizes.  Nevertheless, we should strive for healthy behaviors and healthy eating which could improve outcomes.

Iron Injectables

At bottom of post, more information on COVID-19.

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At a recent Pharmacy, Nutrition, and Therapeutics (PNT) meeting, one of the topics that we reviewed was injectable iron agents, primarily iron sucrose (Venofer ®) and ferric carboxymaltose (Injectafer®).  Iron dextran is mainly used as a supplement in parenteral nutrition in our patient population.

Also, this topic is reviewed in Practical Gastroenterology Jan 2020 (M Auerbach et al. January 2020 • Volume XLIV, Issue 1: Treatment of Iron Deficiency in Gastroenterology: A New Paradigm

Key points:

  • Venofer® is much less expensive and currently has an FDA indication for children. To provide 1500 mg, Venofer®, 5 doses of 300 mg (~$75/dose)~$375. Injectafer®, 2 doses of 750 mg (~$600/dose) ~1200.  This does not include potential travel and other ancillary costs.
  • Dosing: Injectafer® can give large amounts of iron; in adults, typical dose is 750 mg given 7 days apart (in children 15 mg/kg/dose with 750 mg max).  FDA approved method is to administer over 15 minutes. Venofer® in children is 5-7 mg/kg/dose with 300 mg max per dose.
  • Injectafer® has been associated with hypophosphatemia (in 27%, <2 mg/dL); Hypophosphatemia has also been reported with iron sucrose.  The reported incidence of hypophosphatemia is higher with ferric carboxymaltose vs iron sucrose.
  • Other Adverse Effects
Iron Sucrose (Venofer®) Ferric Carboxy (Injectafer®)
Nausea 8.6% 7.2%
Vomiting 5% 1.7%
Diarrhea 7.2% <1%
Dizziness 6.5% 2%
Hypertension 6.5% 3.8%

Oral vs IV Iron for IBD: Auerbach et al recommends that “iron should only be given orally to IBD patients with inactive disease, mild anemia, and good tolerance of oral iron; in patients with active IBD oral iron should be avoided.”  They state that “oral iron has been shown to exacerbate intestinal inflammation of IBD independent of anemia, and cause luminal changes in microbiota and bacterial metabolism, which may negatively alter the microbiome.” (Has IV iron’s effect on the microbiome been studied/compared to oral iron?)

Safety of intravenous iron: “In a recent meta-analysis, the results of more than 10,000 patients who were treated with intravenous iron were reported. Compared to oral iron, placebo, and even intramuscular iron (which should never be given), while minor infusion reactions were observed with IV iron, there was no increase in serious adverse events compared to any comparator including placebo.”

My take: Injectafer® is likely preferable to Venofer® in the outpatient setting as adequate dosing can be given in 1 or 2 infusions.

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Trail on Blood Mountain

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  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

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Here’s a link to Financial Times COVID-19 Tracker –includes logrithmic charts plotting the rates of reported infection and deaths and allows quick comparison between countries and high-volume locations (eg. Madrid, Lombardia, NY City).  Some figures from March 23, 2100 GMT noted below; unfortunately, the U.S is likely to the world leader in number of reported cases quite soon.

Other relevant tweets: