Teaching an Old Liver New Tricks

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A recent retrospective study (JD de Boer et al. Liver Transplantation 2019; 25: 260-74) helps address the question of whether/when a geriatric liver is too old for donation.

The authors culled data from 2000-2015 from 17,811 first liver transplantations performed in the Eurotranplant region.

Key findings:

  • 2394 (13%) transplants were performed with livers ≥70 years old
  • Graft survival was reduced from donors with a history of diabetes (HR 1.3) and in recipients with hepatitis C virus (HCV) antibody (HR 1.5)
  • “Although donor age is associated with a linearly increasing risk of graft loss between 25 and 80 years old, no differences in graft survival could be observed when “preferred” recipients were transplanted” with older grafts (HR 1.1).
  • Preferred recipients: 1. HCV-Ab neg, 2. Recipient >45 years old, 3. BMI <35 kg/m2, 4. cold ischemia time < 8 hours. 26% of recipients were considered “preferred” recipients
  • Utilization of livers from donors ≥70 years old increased from 42% (2000-2003) to 76% (2013-2015).
  • The median donor age increased from 42 to 55 years old from 2000 to 2015.
  • The oldest transplanted liver was 98 years old!

The overall Kaplan-Meier survival curves are given in Figure 2 and there is a clear trend of better graft and patient survival with donors <70 years of age.  However, Figure 4 shows that graft survival with “preferred” recipients was essentially identical when comparing grafts from donors <70 compared to >70.  However, when comparing graft survival from donors <40 compared to donors >70, there appeared to be a small advantage for the younger organs, though this did not meet statistical significance. (HR 1.2 CI 0.96-1.37).

My take: Given the shortage of available livers, the use of older donor organs is a necessity and can be accomplished without significant loss of grafts in selected patients.

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Tackling High Drug Costs -Lessons from Australia and Brazil

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In two related commentaries referenced below, the authors detail how Australia and Brazil managed to provide a blockbuster hepatitis C virus (HCV) medication without following the going-broke example of Blockbuster video stores.

  • Australia: S Moon et al. NEJM 2019; 380: 607-9
  • Brazil: EM da Fonseca et al. NEJM 2019; 605-6.

Australia provided a lump-sum payment of approximately 770 million dollars (in U.S.) over 5 years in exchange for an unlimited volume of direct-acting antivirals (DAAs). As a result of this approach, Australia managed to treat many more patients at a much lower cost.  “The government would have to spend …U.S. $4.92 billion more to treat the same number or it could treat 93,000 fewer patients with a fixed budget” of approximately U.S. $766 million.

With the Australian approach, the authors note that it is analogous to a patent buyout and works if the ongoing drug manufacturing cost is low and the manufacturer is able to meet growing volume demand.

Brazil’s approaches for DAAs relied on either threatening loss of patent protections and/or enabling local generic production of sofosbuvir.  This resulted in ~90% price discount. Patent protection in Brazil is granted only if a medication is approved by both INPI (Instituto Nacional da Propriedade Industrial) and ANVISA (Brazilian Health Regulatory Agency).

My take: Given the rising costs of medicines, examining how other countries surmount these financial barriers is important.  In my view, the often arbitrary and exorbitant pricing by pharmaceutical companies will erode the support of protective policies in the U.S. which thus far has helped produce many advances.

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Why Fiber Matters?

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A recent review article (J O’Grady et al. Aliment Phamacol Ther; 2019; 49: 506-15) highlights how fiber is important for health and its potential role in fostering a diverse microbiome. Some of the material has been covered before in a previous blog/presentation: It’s Alimentary!  “The Fiber Movement: Why Kids Need It and How to Get It” by Maria Oliva-Hemker .

In the introduction, the authors note that there had been a period of disappointment that fiber did not seem to help irritable bowel syndrome.  Though with expanding knowledge of the diet-, microbiome- host interactions, clinicians have started to appreciate the health impact of dietary fiber.

In subsequent sections, the authors detail the different types of fiber based on solubility, viscosity and fermentation.

Key actions of fiber:

  • Anti-inflammatory effects
  • Immune system modulation
  • Regulation of cell proliferation and differentiation
  • Richer microbiome diversity (may lower risk of C difficile)

The authors note that a low-fiber diet in germ-free mice can result in a reduced microbial diversity and interestingly, the “missing taxa is transmitted to subsequent generations” even if fiber is re-introduced.

Potential beneficial fiber effects beyond bulking up stools:

  • Reduced adiposity
  • Lower metabolic disease including lower cholesterol and better glucose metabolism
  • Lower incidence of chronic inflammatory diseases
  • “Potential for fiber to prevent… diverticular and neoplastic disorders”

Western Diet is Deficient in Fiber.

  • Recommendations for fiber intake of 14 g per 1000 kcal consumed, which equates to approximately 25 g for females and 38 g for males (depending on energy intake).
  • In underdeveloped countries and historically, intakes are more than 50 g (in Africa) and up to 100 g/day in ancestral humans
  • Actual intake in U.S. is only 12-18 g/day.

The authors recommend efforts to gradually titrate increased fiber in the diet as abrupt changes may be poorly tolerated due to gas and bloating.

My take: This article explains that the connection between fiber intake and a number of health outcomes is likely due, at least in part, to its modulation of the microbiome. Thus, fiber is important for much more than a good poop.

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NY Times: Five Things I Wish I’d Known Before My Chronic Illness

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A recent article describes some of the challenges of dealing with Crohn’s disease (thanks to Kayla Lewis for pointing out this reference).

NY Times: Five Things I Wish I’d Known Before My Chronic Illness

Key Points:

  • “Your relationships change” “It’s hard to be a good employee when you need extended time off. It’s hard to be a good friend when you cancel plans last minute. It’s hard to be a good partner or parent when you barely have the energy to get out of bed. “
  • “Everyone offers you advice” “So unless someone asks for your advice, don’t offer it. If you’re on the receiving end of misguided advice, say something like, “I appreciate that you’re trying to help, but my doctors and I think this treatment is best right now” or “There’s no known cure for my disease, but I’d love if you donated toward the research to find one!”
  • “You have to educate yourself — and everyone else“
  • “Support is everything”  Online communities can be helpful. ” The Crohn’s and Colitis Foundation has resources to help you find one. For a sometimes embarrassing “bathroom disease” like IBD, this is especially vital.”

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Economic Costs of Gluten Free Diet

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A recent study (AR Lee et al. Nutrients; 2019, 11, 399). Open access: Persistent Economic Burden of the Gluten Free Diet) quantifies the additional costs of a gluten free diet (GFD) in the U.S. Thanks to Kipp Ellsworth for this reference.

The authors conducted a “market basket” study to establish the cost of a GFD. “A market basket is a group of products that are purchased by consumers …for this study, the market basket was food that would necessitate a GF substitute, including staple foods, snack foods, and commonly used ready-made or convenience meals.”

Key findings:

  • GF products were more expensive, overall the increase was 183%.  This is an improvement from a 2006 study which found the increase overall at 240% (adjusted for inflation).
  • Mass-market products were 139%  more expensive than wheat-based versions

Discussion:

  • Cost is identified as a frequent reason for nonadherence with diet, cited by 33% in one study
  • Overall, the burden of GFD is more frequently related to the restrictive nature of the diet which leads to a negative impact on quality of life. According to the authors, in one study (Am J Gastroenterol 2014; 109: 1304-11), treatment burden for celiac was ranked higher than for diabetes hypertension, and congestive heart failure

My take: This study shows the significant economic burden of a GFD.  In Italy, the  “government offers celiac patients vouchers to buy gluten-free food — up to 140 euros per month.” (NPR: Italy, Land of Pizza and Pasta)

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AAP -Behind the Scenes 2019

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The Georgia Chapter of the American Academy of Pediatrics (AAP) had a recent Board of Directors meeting.  There is a core group of pediatricians and pediatric specialists who, in conjunction with the AAP staff, work to improve the health of children. This includes arranging conferences, working with legislators, identifying regulatory issues and promoting best practices.  The Board of Directors meeting helps guide the chapter’s work.  This year’s meeting covered a lot of ground.  Two of the presentations provided information from the composite medical board and ABP certification/MOC.

The first presentation discussed the following:

  • -How physicians get into trouble: not completing CME credits, drug use, inappropriate contact with patients.  A new issue is not registering for PDMP (prescription drug monitoring program).  If a physician is not in compliance, they will be fined $3000 and reported to national database.
  • -Issue of lack of physician access in rural areas.
  • -High debt of physicians completing medical school and loan repayment programs to encourage physicians to locate in underserved areas.

The second presentation by Anna Kuo and Brad Weselman focused on changes in ABP’s MOC process, including the introduction of MOCA-Peds.  The goal of the changes is to make MOC process more relevant in improving practice.

FDA’s Very Limited Ability to Regulate Dietary Supplements

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NY Times: Supplement Makers Touting Cures for Alzheimer’s and Other Diseases Get F.D.A. Warning

An excerpt:

The Food and Drug Administration on Monday warned 12 sellers of dietary supplements to stop claiming their products can cure diseases ranging from Alzheimer’s to cancer to diabetes.

At the same time, Dr. Scott Gottlieb, the agency’s commissioner, suggested that Congress strengthen the F.D.A.’s authority over an estimated $40 billion industry, which sells as many as 80,000 kinds of powders and pills with little federal scrutiny…

The F.D.A.’s oversight is based on a 1994 federal law, which imposed minimal reporting and labeling requirements on the makers of vitamins, minerals and herbs — a fledgling industry at the time. To prevent a company from selling a product, the law requires the F.D.A. to prove that it is unsafe…

There are now between 50,000 and 80,000 dietary supplements on the market, according to the F.D.A. The agency also says that three of every four American consumers now take a dietary supplement regularly.

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Pushing the Boundaries on Dietary Therapy for Crohn’s Disease (CD-TREAT)

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A recent study (available online in advance of publication) (V Svolos et al. Gastroenterology https://doi.org/10.1053/j.gastro.2018.12.002) examines the feasibility and science of modifying a diet to mimic exclusive enteral nutrition.

Full text accepted manuscript (from ScienceDirect/Gastroenterology website): Treatment of Active Crohn’s Disease With an Ordinary Food-based Diet That Replicates Exclusive Enteral Nutrition (PDF 135 pages)

Background: The authors note that exclusive enteral nutrition (EEN) is the only established dietary treatment for Crohn’s disease.

This complicated study had three main parts:

  1. Examining the effects of their CD-TREAT diet compared to EEN in 25 healthy adults in a randomized control trial
  2. Animal experiments (rat model) to explore the anti-inflammatory effect of CD-TREAT
  3. Pilot open-label study of 5 children with CD-TREAT diet (8-weeks)

In the first part of this study, the authors modeled a diet based on the components of the formula modulen. This diet continued to exclude gluten, lactose, and alcohol and tried matching other components (macronutrients, vitamins, minerals, fiber).  In place of maltodextrin (the commonest carbohydrate in EEN feeds), the authors substituted foods high in starch and low in fiber.  Also, the authors decreased carbohydrates in CD-TREAT (particularly complex carbohydrates) in favor of protein.  This diet was given to 25 healthy adults.

Key findings:

  • CD-TREAT induced similar effects to EEN on fecal microbiome, composition,metabolome, mean total sulfide, pH, and short-chain fatty acids (SCFA)

In the second part of this study, in the rat model, CD-TREAT and EEN produced similar changes in bacterial load, short-chain fatty acids, microbiome, and in ileitis severity.

In the third part of the study with 5 children, after 8 weeks —Key findings:

  • 4 (80%) had a clinical response
  • 3 (60%) entered a clinical remission with concurrent reductions in calprotectin (mean decrease of 918 +/- 555 mg/kg)

The CD-TREAT diet appears to affect the taxon abundance of many species of the microbiome in a manner similar to EEN therapy.  The authors noted that CD-TREAT also changed the abundance of genera belonging to Actinobacteria, Bacteroides, and Firmicutes.

Unlike EEN, the CD-TREAT diet is subject to more variable individual intakes; it is not identical in all individuals.

My take: The mechanism of action of EEN therapy remains poorly understood.  The CD-TREAT diet, which is far more diverse than EEN, appears to replicate many of the effects of EEN: “the microbial composition, fecal pH, SCFA, total sulfide, fecal bacterial load and fecal metabolome significantly changed in the same direction for both diets.” A larger clinical study is needed to confirm the effectiveness of the CD=TREAT diet.

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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

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Sport Drinks Not Needed

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A recent expose from 538 explains why sports drinks are unnecessary.

538: You Don’t Need Sport Drinks to Stay Hydrated

Key points:

  • Though sports drinks are highly marketed, there is little scientific evidence behind their claims
  • Water is generally better for most people
  • Hyponatremia can be provoked by drinking too much fluids

A few excerpts:

  • “As it turns out, if you apply evidence-based methods, 40 years of sports drinks research does not seemingly add up to much,” Carl Heneghan and his colleagues at the University of Oxford’s Centre for Evidence-Based Medicine wrote in a 2012 analysis published in the British medical journal BMJ. ..
  • There has never been a case of a runner dying of dehydration on a marathon course, but since 1993, at least five marathoners have died from hyponatremia they developed during a race.  At the 2002 Boston Marathon, researchers from Harvard Medical School took blood samples from 488 marathoners after the finish. The samples showed that 13 percent of the runners had diagnosable hyponatremia…Athletes who develop hyponatremia during exercise usually get there by drinking too much because they’ve been conditioned to think they need to drink beyond thirst

My take: Drink when you are thirsty.  Exceptional talent and hard work, not sports drinks, are the key if you want to “Be Like Mike.”

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