Improving MRI for NAFLD

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From MedicalNewsToday – a summary of a recent Hepatology study by Jeffrey B. Schwimmer, MD and colleagues.

Excerpts from http://www.medicalnewstoday.com/releases/289088.php along with image.

“In this study, the researchers compared a new MRI technique to the standard liver biopsy method of assessing fat in the liver. To do this, the team enrolled 174 children who were having liver biopsies for clinical care. For each patient, the team performed both MRI-estimated PDFF and compared the results to the standard pathology method of measuring fat on a liver biopsy.”

Screenshot from MedicalNews

Screenshot from MedicalNewsToday

“The team found a strong correlation between the amount of liver fat as measured by the new MRI technique and the grade of liver fat determined by pathology. This is an important step towards being able to use this technology for patients. Notably, the correlation was influenced by both the patient’s gender and the amount of scar tissue in the liver. The correlation between the two techniques was strongest in females and in children with minimal scar tissue.”

“Depending on how the new MRI technology is used, it could correctly classify between 65 and 90 percent of children as having or not having fatty liver tissue.”

“… However, further refinements will be needed before this or any other MRI technique can be used to diagnose NAFLD in an individual child.“

Infantile Hemangioma -Propranolol Effective

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While infantile hemangiomas are not much of a GI disorder, I still thought a recent article (NEJM 2015; 372; 735-46) merited a brief mention. This trial included 456 patients who received treatment in a randomized, double-blind trial.

Key finding: “this trial shows that oral propranolol at a dose of 3 mg per kilogram per day for 6 months is effective in the treatment of infantile hemangioma.”

  • Successful treatment noted in 60% compared with 4% of placebo patients.
  • 88% of propranolol patients showed improvement by week 5 compared with 5% in placebo group.
  • Eligible patients between 35-150 days had a proliferating hemangioma requiring systemic therapy with a minimal diameter of 1.5 cm.

Short Takes on IBD Articles

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Singh S, et al. Gastroenterol 2015; 148: 64-76.  In this study, the authors identified 21 trials with 2006 participants to examine the comparative efficacy of pharmacologic interventions to prevent relapse of Crohn’s disease (CD) after surgery.  Conclusion: “anti-TNF monotherapy appears to be the most effective strategy for postoperative prophylaxis for CD.” The relative risk of clinical relapse and endoscopic relapse with anti-TNF monotherapy was estimated to be between 0.02-0.20 and 0.005-0.04, respectively. Thus, those at highest risk for recurrence, including younger individuals, smokers, penetrating CD, perianal CD, and recurrent surgeries) are most likely to benefit.(Related blog post: More Lessons in TNF Therapy (Part 1) | gutsandgrowth)

Pariente B, et al. Gastroenterol 2015; 148: 52-63. The researchers in this cross-sectional study developed the Lémann Index which measures cumulative structural bowel damage in patients with CD.  My only complaint with this study was the associated editorial on pages 8-10, titled “The Holy Grail, or Only Half Way There?”  There are too many medical advances compared to ‘the holy grail’ and, in my opinion, this shouldn’t be one of them.

Zitomersky NL et al. Inflamm Bowel Dis 2015; 21: 307-14.  In this study the authors examine the relationship between the development of antibodies to infliximab (ATI) and the risk of surgery in a cross-sectional cohort of pediatric and young adult patients.  Not surprisingly, development of ATI, which was noted in 20% of cohort, correlated with reductions in infliximab levels and higher risk of surgery.  Interestingly, prior (but not current) immunomodulator therapy was associated with lower antibody levels (P=0.007).  Perhaps, “step-up” therapy may lower the risk of ATI. (This was a point noted by James Markowitz in a previous post: More NASPGHAN Meeting Notes: IBD Hot Topics | gutsandgrowth)

Rogler G, Vavricka S. Inflamm Bowel Dis 2015; 21: 400-08. This review article discusses the exposome in IBD.  Exposures include air pollution, diet, drugs, infections, water pollution, food additives, and smoking.  These exposures influence the gut microbiome and genetic susceptibility. “Only environmental influences…explain the rising incidence in IBD worldwide. The investigation of the exposome…is an enormous challenge…[but] of crucial importance.” (Related blog post: What do you know about the “exposome”? | gutsandgrowth)

Kalmon RS. Inflamm Bowel Dis 2015; 21: 428-35. Review article provides information when there is a prior personal or family history of malignancy (=avoid thiopurines).  Figure 2 is a suggested algorithm for those with IBD and a previous diagnosis of cancer.

  • In those in which the cancer is adequately controlled, the recommendations indicate that if it has been more than 2 years since completion of therapy to use a ‘step-up’ management and favor methotrexate over thiopurines
  • In those with less than 2 years since completion of cancer treatment and not responsive to 5-ASAs/antibiotics, then “consider monotherapy with biologic agents.”
  • In those still receiving chemotherapy, the authors suggest “hold immunosuppression and follow course of IBD.  If IBD not well controlled despite chemotherapy, 5-ASAs and antibiotics, treat flares with steroids, then consider biologic agents.”

More Evidence of Anesthetic Neurotoxicity

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One of the more troubling commentaries that I read recently (Rappaport BA et al NEJM 2015; 372: 796-97) provides additional insight into the issue of anesthetic neurotoxicity.

The possibility that anesthetic agents could result in learning disabilities and other neurologic impairments is not new (Pediatrics 2011); however, the data has become more concerning.

Key points:

  • “Compelling evidence from animal models is supported by a small number of observational studies in children who underwent anesthesia early in life.” Exposure to multiple (but not single) episodes of anesthesia and surgery were associated with increased risk of learning disabilities.
  • Anesthetics which have been implicated include propofol, ketamine, sevoflurane, etomidate, desflurane, and isoflurane.  Histologic changes, in animal models, have included apoptosis and cell death, changes in neuronal morphology, and decreased number of synapses.
  • “In June 2014, SmartTots convened a meeting…the participants concluded that the current data from animal studies are now sufficiently convincing that large-scale clinical studies are warranted.” SmartTots Consensus Statement
  • “Care providers should be made aware of the potential risks that anesthetics pose to the developing brain…and parents should consider how urgently surgery is needed, particularly in children under 3 years of age.”

Take-home message:  While recognizing that confounding variables make it difficult to be certain, it appears that anesthetics (particularly prolonged or repeated courses) can result in neurologic changes.  There is enough information available to recommend avoiding truly elective procedures which require anesthetics in young children.

 

Dropping Weight by Adding Fiber in Diet

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A recent study showed that increasing fiber in the diet helped participants lose weight.  The details are noted in this LA Times story: To lose weight, experts suggest a focus on fiber

Here’s an excerpt:

If you’re trying to lose weight, you could count your calories, keep track of precisely how much salt and sugar your eat, and make sure you hit certain targets for protein, carbohydrates, cholesterol and the various types of fat. Or you could set all of that aside and concentrate on just one thing: Eating at least 30 grams of fiber each day.

In a yearlong clinical trial involving 240 obese people who had metabolic syndrome, those who focused on fiber lost almost as much weight as those who followed the American Heart Assn.’s extremely detailed dietary recommendations.

Related blog posts:

Some funny headlines form Freakomomics website –here’s one:

Screen Shot 2015-02-22 at 9.35.46 AM

 

“Mutant Ninja Viruses”

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Yesterday’s post “Understanding HCV Treatment Failures with Sofusbuvir” provided a summary of why patients with hepatitis C virus (HCV) genotype 3 may not respond to therapy. Now a terrific article (Hepatology 2015; 61: 471-80, editorial, titled “Mutant Ninja Viruses” 421-23) looks at why some patients with the favorable HCV genotype 2 may fail to respond.

By using extensive genotyping data and sequencing, the authors were able to determine why some patients with genotype 2 did not respond to combination therapy with ribavirin/sofusbuvir.  These patients were characterized by as genotype 2 based on Siemens VERSANT HCV Genotype INNO-LiPA 2.0 Assay.  This assay “looks at conserved sequences in the 5′ region of the virus.” However, these patients were genotyped as well using a technique to examine the 3′ region of the virus.  From among more than 2000 samples, the two assays gave divergent results in 0.5% of the cases with the 5′ end indicating genotype 2 and the 3′ end indicating genotype 1.

What is happening?

  • Detailed analyses of these discordant viruses showed that they were hybrid viruses with a crossover point located in the NS2/NS3 region.
  • In patients with these hybrid viruses, only 3 of 11 responded to therapy, indicating that they behave like genotype 1 patients.

Bottomline: “These novel viruses are true viral Ninjas hiding a challenging array of ‘difficult-to-cure’ genotype 1 enzymes under an ‘easy-to-cure’ genotype 2 coat.

Understanding HCV Treatment Failures with Sofusbuvir

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While the new treatments for hepatitis C have improved dramatically in terms of cure rates and side effects (and pharmaceutical companies bottom-line), there are still patients who do not respond, especially those with genotype 3.  A recent study (Hepatology 2015; 61: 56-65) has provided some information into why this is happening.

A division of the FDA looked into five sofosbuvir (SOF) trials and performed sequencing to characterize potential resistance-associated substitutions.

Key findings:

  • Nonstructural protein 5B (NS5B) substitutions, L159F and V321A, emerged in 2.2%-4.4% of subjects who failed SOF treatment.
  • Baseline substitutions in 316 were associated with a reduced response in HCV genotype 1b subjects.
  • This study identified only 11 patients with genotype 3 with potentially relevant substitutions.

Bottomline: In the vast majority of patients, no resistance-associated substitution could be identified, indicating that we have a lot to learn why some patients are not responding.

Related blog posts:

Theses Eggs Contain Eggs!

Theses Eggs Contain Eggs!  Is the “allergen information” really necessary in this case?

An Oral Oligonucleotide in the Crohn’s Treatment Pipeline & Smart Patients

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The preliminary data are in from a phase II study regarding Mongerson, a oral pill for Crohn’s disease.

Here’s the link: Oral oligonucledotide shows efficacy, safety in Crohn’s

Here’s an excerpt from GI & Hepatology News:

Fourteen days of daily treatment with mongersen, an oral, antisense oligonucleotide, safely produced remissions in two-thirds of patients with Crohn’s disease in a phase II study with a total of 163 patients…

Mongensen “is not an anti-inflammatory drug. It removes a brake on the normal immunosupressant mechanism in the gut, and that is why the effect is long lasting. It allows TGF [transforming growth factor]-beta to work again [as an endogenous immunosuppressant] and promote healing,” said Dr. Monteleone, a professor of gastroenterology at the University of Rome Tor Vergata.

Oligonucleotide blockade of the production of the Smad7 intracellular protein prevented the inhibitory effect of Smad7 on TGF-beta and thus allowed TGF-beta to inhibit cytokine production and T lymphocyte signaling (J. Clin. Invest. 2001;108:601-9).

From ImproveCareNow — Smart Patients Online Community -may be helpful resource for families:

There are many social networks and online communities for IBD, but we have chosen to partner with the Smart Patients team because their custom-built, disease-specific forums offer a truly safe, warm and engaging experience for users. Smart Patients also offers conversation tagging, and clearly defined community norms, which means community members are highly likely to find the answers they need and highly unlikely to be trolled. And because the conversations are arranged using tags and completely searchable, you can always find what you’re looking for.

The Smart Patients team and ImproveCareNow have partnered to create an online IBD community that is supportive and also powerful. The Smart Patients IBDcommunity has the power to improve health and health care systems through patient and family peer-to-peer learning.

 

Updated Guidelines on Genetic Testing/Management for Hereditary GI Cancer Syndromes

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Here’s a link to abstract: Updated Guidelines on Genetic Testing/Management for Hereditary GI Cancer Syndromes (The American Journal of Gastroenterology 110, 223-262 (February 2015) | doi:10.1038/ajg.2014.435).  This ACG guideline specifically discusses genetic testing and management of Lynch syndrome, familial adenomatous polyposis (FAP), attenuated familial adenomatous polyposis (AFAP), MUTYH-associated polyposis (MAP), Peutz–Jeghers syndrome, juvenile polyposis syndrome, Cowden syndrome, serrated (hyperplastic) polyposis syndrome, hereditary pancreatic cancer, and hereditary gastric cancer.

I glanced at the guideline –it is about 40 pages in length.  It provides a lot of in-depth information on these infrequent disorders.

Some online resources for similar information:

Family Meals –Protection Against Obesity?

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According to a 10-year longitudinal study, increased family meal frequency during adolescence was associated with a reduced odds of overweight or obesity (Berge JM et al, J Pediatr 2015; 166: 296-301, editorial 220-21).

The data from this study derived from Project EAT I and EAT III which examined at baseline middle school and high school students at 31 public schools in Minnesota.  Ultimately the participants (n=2117) were followed over 10 years.

Key finding:

  • “Results showed that eating family meals together, ranging from 1-2 to 5 or more times during 1 week, was significantly predictive of lower odds of being overweight or obese 10 years later.”  This effect was largest among African American participants.
  • Odds ratios for overweight/obesity was similar with any frequency of family meals compared to no family meals: 1-2 times/week OR 0.67, 3-4 times/week OR 0.50, and 5 or more/week OR 0.68

Why does this occur?

There is not an answer to this question.

Speculation from the authors:

  • “Healthier meals”
  • “Opportunities for emotional connection”
  • “Parental modeling”

In my view, family meals may be an epiphenomenon.  It may be a marker for a more organized household which is likely to have some favorable effects.

Bottomline: Another reason to eat together.  Besides having a chance to catch up on your kids, it may keep them healthier.

Related blog posts: