Survival Advantage of Living Donor Liver Transplantation in Large Pediatric Cohort

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Yodoshi, T., Kuenzig, M. E., Tang, F., Kajiwara Saito, M., Zizzo, A., Ng, V. L., & Benchimol, E. I. Liver Transplantation 2026, 32(9), 1273–1284. Donor type, social deprivation, and long‑term outcomes in pediatric liver transplantation: A 30‑year population‑based cohort.

Background: Living donor liver transplantation (LDLT) reduces wait‑list mortality in children; this can be due to shorter waiting times, minimal cold ischemia, and healthier donor organs. However, its long‑term advantages over deceased donor liver transplantation (DDLT) and how socioeconomic context shapes outcomes in a universal healthcare system (Canada) remain uncertain. Families with socioeconomic disadvantages may have significant barriers to accessing living donor liver transplantation (LDLT). In additon, caregiver resources, neighborhood deprivation, and health literacy may negatively impact post-transplant outcomes.

Methods: From 1991 to 2021, clinical data was linked to provincial health administrative data, yielding 449 recipients who underwent their first transplant. There were 189 LDLT and 260 deceased donor liver transplantation (DDLT).

Key findings:

  •  LDLT recipients had superior patient and graft survival. DDLT was associated with a higher risk of mortality [adjusted hazard ratio (aHR) 2.1], graft failure (aHR 2.1), and chronic kidney disease (adjusted subdistribution HR 5.3), compared with LDLT.
  • The absolute survival advantage of 10-15% at 10 years persisted into the third decade.
  • LDLT outcomes were less impacted by the socioeconomic disadvantages, with recipients showing comparable outcomes regardless of their SES.
  • The overall incidence of de novo cancer was low (2-3% at 10 years post-LT; most of these cancers were due to PTLD.
  • Limitations: The survival advantage could be in part due to selection bias. Patients with more urgent conditions like PALF were more likely to be DDLT recipients. In addiiton, this study did not adjust severity of illness at time of transplantation.

My take: LDLT is underutilized. More use of LDLT will result in better outcomes.

Related blog posts:

Neurocognitive Deficits in 30% of Short Bowel Cohort

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RAL Duister, LE Vlug et al. J Pediatr Gastroenterol Nutr. 2026;83:404–411. Open Access! Cognitive assessment in children with intestinal failure on and weaned off parenteral nutrition

This multicenter international cross-sectional study of children with IF (n=50) examined neurocognitive outcomes (2019-2024); all children were currently receiving home PN or having a history of home PN-dependency.

Key findings:

  • The most common underlying condition was necrotizing enterocolitis (28%); other etiologies included intestinal atresia (20%), midgut volvulus (10%), and intestinal pseudo-obstruction (12%)
  • 21/50 children (42%) received home parenteral nutrition (PN); median PN-duration was 26.8 (7.5–66.5) months
  • Median IQ score was 92.0 (74.3–101.0); 15 children (30%) had very/extremely low IQ (</= 79), both significantly different from the normal population (p < 0.001)

My take: This study provides a good estimate of the percentage of children with intestinal failure/short bowel syndrome with significant neurocognitive impairment: about 30%. The likelihood would be higher in those with proven neurological insults.

Related blog posts:

Seljalandsfoss with a 200 foot watefall cascade. Iceland

Dr. Barbara McElhanon: Update on Autism and GI Manifestations

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Recently, Dr. Barbara McElhanon gave our group a terrific update on the GI Manifestations Associated with Autism. My notes below may contain errors in transcription and in omission. Along with my notes, I have included many of her slides.

  • Even with the early descriptions of autism, dating back to Les Kanner in 1943, gastrointestinal complaints like feeding difficulties/peculiar diets were recognized.
In a 1971 study, Barry Goodwin reported that seven of the 15 autistic children he had randomly selected from a local community for his study had chronic diarrhea. He found that placing these children on a gluten-free diet improved GI symptoms, as well as abnormal EEG findings.
  • Some studies have found an increase in some autistic behaviors (greater impairment in sleep, communication sensory processing and repetitive behaviors) in those with coexisting/worse gastrointestinal symptoms.
Patients with ASD had much more frequent GI complaints than the control group from this recent prospective longitudinal study at UC Davis looking at almost 500 kids
More than 50% of participants with ASD had GI symptoms at all time points
  • More than 1000 genes have been associated with developing autism.  About 90% of these genes have expression outside the central nervous system including the enteric nervous system.
There are some genes that are implicated in both autism risk and known GI problems. There is elevated serotonin in these patients which plays an important role in both the central and enteric nervous systems.
  • No unique microbiome has been identified as being associated with autism.  Fecal microbial transplantation (FMT) studies included an open label study suggesting an improvement in gastrointestinal symptoms and mood.  However, a randomized study with oral FMT found no changes except some improvement in socialization.
  • For now, FMT is not an established therapy for autism and probiotics are not recommended.
  • Dr. McElhanon notes that dietary restrictions are not recommended for autism.  Children with autism often have a restricted diet at baseline and further restrictions can increase the likelihood of feeding disorders like ARFID.
  • Dr. McElhanon notes that this administration has made several recommendations regarding autism; this has increased awareness and attention to children with autism.  However, at this time, the Marcus Center does not recommend the use of Leucovorin. The studies that have purported to show benefit were small studies with varying doses.  This medication has had an increase in usage due to the increased awareness. 
  • With regard to acetaminophen, recent large studies have shown that it is safe to use and has not increased the risk of autism after use by pregnant women.
  • Due to atypical diets, vitamin/nutrient deficiencies are not rare in children with autism and dietary restrictions.  Disorders like scurvy (Vitamin C deficiency) need to be considered in this population.  Vitamin supplements (eg. NanoVM which is tasteless) are important to prevent these deficiencies.
  • For clinical care, Dr. McElhanon prefers to get a good history before delving into the potentially extensive testing that families may bring.  Also, additional time for the visit and to discuss treatment are needed.  In children with autism, due to difficulty administering medications and diet, it can take longer to figure out the right option.
  • More research on optimal treatment is ongoing.

Related blog posts:

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.

Elegant Study: Childhood Exposure to a Sibling with Crohn’s Disease and Disease Susceptibility

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R Chen et al. Gut. Epub ahead of print, August 31, 2026. doi:10.1136/
gutjnl-2026-339257. Childhood exposure to a sibling with Crohn’s disease alters gut microbiome and Crohn’s disease susceptibility

Thanks to Mike Hart for sharing this reference. This study is worth reading in its entirety due to the combination of experiments. This is a fairly long post to summarize the most important findings.

Background:

“In a study of 2756 Dutch families, gut microbiome composition and function were more alike between siblings than between parent-offspring pairs or spouses…These findings suggest that increased disease susceptibility among siblings of individuals with CD may be mediated by their shared gut microbiome.”

Methods:

  1. The authors used the prospective Genetic Environmental Microbial (GEM) Project and the nationwide South Korean database to assess the association between childhood exposure to affected siblings and CD onset (n=3126). This was validated in the South Korean dataset.
  2. A T-cell transfer model of colitis in germ-free mice was conducted to investigate the effects of stool from childhood-exposed (n=4) versus adult-exposed (n=4) siblings.
  3. An integrative risk model combining faecal calprotectin (FCP) and microbial enterotypes was trained and internally validated within the GEM cohort.

Key findings:

  • “In the GEM cohort, childhood exposure to an affected sibling was associated with a fourfold higher risk of developing CD compared with adult exposure (adjusted HR (aHR) 4.00; p=5.3×10−4), which was validated in the South Korean dataset (aHR 2.54; p=6.0×10−6).”
  • “Childhood exposure was associated with reduced abundances of Lachnospira,
    Roseburia     and Colidextribacter, reductions that mediation analysis identified as partially mediating CD risk.”
  • “In vivo, transplantation of childhood exposure-associated microbiota into germ-free recipient mice exacerbated colitis and elevated mucosal interleukin-22 expression, supporting a potential mechanistic role.”
  • This “model identified siblings with elevated FCP and Blautia-enriched or
    Prevotella-enriched enterotypes as highest risk, with a 10-year cumulative incidence of 22.5%.”
Figure 1b. Childhood exposure to CD was demonstrated to associate with increased disease susceptibility in the GEM cohort, and confirmed in an independent nationwide dataset.
Figure 1d. Among siblings with childhood exposure to CD, the authors developed and validated a risk stratification based on gut inflammation and enterotypes to identify individuals at high risk of CD onset
Figure 3a. Bar chart presenting the proportion of individuals with gut barrier dysfunction and gut inflammation among those exposed to CD during childhood (blue) or adulthood (orange).
Figure 5d. Kaplan-Meier curves showing the cumulative CD-free probability for individuals classified as having non-inflammation (blue), gut inflammation with Bact2 (green) and gut inflammation with Blau/Prev (orange) in the GEM cohort.

Discussion

  • This “study demonstrates that the timing of exposure to a sibling with CD, specifically childhood versus adult exposure, plays a critical role in disease susceptibility. Childhood exposure was associated with a fourfold higher risk of CD, potentially mediated by alterations in the gut microbiome.”
  • “Genetic predisposition has traditionally been considered the primary explanation for the elevated disease risk among siblings of persons with CD. However, genetic factors account for only about 10% of the variance in CD risk…childhood exposure to a sibling
    with CD, compared with adulthood exposure, was associated with a fourfold increased risk of disease onset, independent of the CD-PRS [CD – polygenic risk score].”
  • This study adds to “a growing body of evidence [that] implicates early-life exposures in CD pathogenesis. A recent meta-analysis reported that prenatal exposure to antibiotics and cigarette smoking increased the risk of CD, while breastfeeding was protective. Similarly, a large population-based study found that rural residence during childhood, but not adulthood, was associated with a lower risk of CD.”

Limitations:

  • Participants were from high-income countries.
  • Study did not include dietary intake.
  • These findings do not prove causation. There may be additional unrecognized genetic factors between the groups with exposure before and after 18 years of age.

My take: The increasing prevalence of Crohn’s disease, particularly over the last few decades, must be related to environmental factors; population genetics and genetic predisposition are unlikely to rapidly change. This is a very important study supporting the notion that exposure to siblings with Crohn’s disease and alteration of the gut microbiome increases the risk of Crohn’s disease. By identifying a microbiome group with a higher risk, this study may facilitate research to determine whether manipulation of the gut microbiome could reduce the likelihood of developing Crohn’s disease. If we can reduce Crohn’s disease in a high risk population, it may allow broader use of the same treatment principles to lower risk groups as well.

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Audio-Recorded Gut-Directed Hypnotherapy for Disorders of Gut-Brain Interaction Plus Measles Update

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L Barash et al. J Pediatr Gastroenterol Nutr. 2026; doi.org/10.1002/jpn3.70545. The role of audio‐recorded gut‐directed hypnotherapy onsleep and abdominal pain: A pilot and feasibility study.

Background: Gut-directed hypnotherapy (GDH) is an evidence-based treatment that improves abdominal pain and quality of life in pediatric DGBI both in the short- and long term.3, 4 Home-based audio-guided GDH has shown comparable efficacy to in-person treatment, while enhancing access to care for families with logistical or socioeconomic barriers.5, 6 

Methods: This was a non-blinded randomized controlled trial with partial crossover. Treatment includes three 25-min audio sessions every 2 weeks and daily 10–20-min sessions, with a goal of ≥5 sessions per week. Out of 25 participants who initiated GDH 16 (64%), completed treatment. Reasons for dropout included side effects (nausea, n = 2), lack of improvement (n = 1), resolution of symptom (n = 1), and unknown (n = 5).

Key findings:

  • Combined abdominal pain scores significantly improved post-treatment with GDH, with a 40.2% reduction from baseline (p < 0.001; d = 0.9), compared to a 16.6% reduction in the standard medical therapy (SMT) group
  • The SMT group had no improvements in sleep-related impairment (SRI) (p = 0.90) … whereas those who completed GDH demonstrated significant improvements in SRI at both 4 weeks (p = 0.01) and at the completion of treatment (p = 0.01)
  • Two participants in our study discontinued due to worsening nausea. Many of the audio recordings included motion-related imagery, which may have contributed to symptoms in susceptible participants.

In a separate study (n=230) (JTW Snijkers et al. Gut Published Online First: 25 July 2026. doi: 10.1136/gutjnl-2026-338385. Open Access! In-person therapist-delivered hypnotherapy versus smartphone-based self-guided hypnotherapy in IBS: a multicentre three-armed randomised controlled trial), a self-guided smartphone hypnotherapy program did not meet the prespecified threshold for noninferiority to in-person hypnotherapy for abdominal pain response in patients with irritable bowel syndrome (IBS). At weeks 13-16, Food and Drug Administration-defined abdominal pain response rates were 48.1% with in-person therapist-delivered hypnotherapy, 33.3% with smartphone-based self-guided hypnotherapy, and 21.8% with online psychoeducation. 

My take (borrowed in part from the JPGN authors): “Providers may consider GDH as a low-risk, home-based therapeutic option for children with DGBI, particularly when sleep is also a concern.”

Rigorous pharmacologic studies show that medications, to date, recommended for patients with DGBIs have difficulty outperforming placebo. With hypnotherapy, having an adequate control group is problematic. It would not be surprising, though, for GDH to have difficulty outperforming pharmacologic agents/placebo despite its good response in patients with DGBIs. In this setting, the use of GDH or medications with a low incidence of adverse effects and plausible beneficial effects continue to have a role in improving symptom control.

From AGA Today: US Measles Outbreak Tops 3,000 Cases Reaching 35-Year High

NBC News (9/4, Edwards) reports, “A 6-week-old baby girl is one of two people with measles who died in Pennsylvania, the Lancaster County coroner said Friday, as the nation’s measles tally hit a new 35-year record of 3,134 cases. … At least 115 more people in Pennsylvania, mostly in Lancaster County, have been diagnosed with measles in the last week, the health department said Friday, bringing the state’s outbreak to about 577 cases within the last few months.” Experts say there are likely many more across the country who have contracted measles but have not gotten tested. NBC adds, “The new milestone, the highest number of confirmed cases since 1991, is yet another indication that the highly contagious virus is taking over, particularly in areas of the country with plummeting vaccination rates.”

Related blog posts (for DGBIs):

Related blog posts (for Measles)

Blog Case Report: Eosinophilic Colitis

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This past month I helped diagnose a 2nd young child with eosinophilic colitis. This was an 8 month old who developed rectal bleeding over a 6 week period with subsequent anemia (Hgb 7.1). His colonoscopy showed patchy deep erythema in the right colon and transverse colon; his biopsies identified >100 eosinophils/hpf.

This prompted me to review a case of a child presenting with eosinophilic colitis at 13 months of age.

Case study: He was born at 36 week gestation with a prenatal diagnosis of proximal bowel obstruction due to type IIIb jejunal atresia, s/p ex-lap and tapering enteroplasty for long dilated jejunal segment and with subsequent short gut syndrome (~50 cm of small bowel). He required supplemental HAL dependency for his initial 9 months of life. At 13 months of age, he developed bloody diarrhea (up to 12/day) with associated anemia and peripheral eosinophilia (max elevation of AEC during his course was 23,000).

Initial endoscopy took place in January 2022. Images are noted below and histology confirmed eosinophilic colitis (>100 eos/hpf).

He underwent extensive testing and no monogenetic/immune dysregulation disorders were identified. After not improving with an elemental diet, his treatment ​consisted of prednisolone along with enteral antibiotics (vancomycin/gentamicin)​. His symptoms recurred with steroid taper and he was changed from antibiotic therapy to mesalamine. This was also ineffective. Subsequently, he started with vedolizumab therapy.

Due to ongoing symptoms, tacrolimus (along with PCP prophylaxis) was added two months later (this was 4 months after initial colonoscopy). The target level was between 8-10. He had a rapid and sustained response allowing him to stop corticosteroids which had been used intermittently for more than 6 months. His vedolizumab was stopped shortly thereafter.

After a followup panendoscopy demonstrated resolution of his colitis (see image below), his diet was gradually advanced (no restrictions) while continuing tacrolimus.

His tacrolimus was discontinued after 2.5 years and he has continued to do well off therapy for two years at this point. He still requires periodic vitamin-micronutrient monitoring for his short bowel syndrome.

My take: Eosinophilic colitis is a rare disorder in pediatrics with sparse data to guide management. In this young pediatric patient, tacrolimus was effective. It is possible that vedolizumab would have been effective if given for a longer duration prior to administration of tacrolimus. At the time of presentation, dupilumab had not been approved for eosinophilic esophagitis. There have been case reports of its use off-label for eosinophilic colitis (T Sia et al. Clin Transl Gastroenterol. 2025 Aug 26;16(10):e00908. Dupilumab for Adult and Adolescent Patients With Primary Eosinophilic Colitis).

Related blog posts:

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.

Immune Mediated Enterocolitis with CAR-T Cell Therapy

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JA Damianos et al. Alimentary Pharmacology & Therapeutics, 2026; 0:1–12. Open Access! Review Article: Immune Effector Cell-Mediated Enterocolitis Following CAR-T Cell Therapy—Clinical Features, Pathophysiology and Management

Background: “Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of hematologic malignancies, and its use is expanding rapidly into numerous other disease states including autoimmune diseases. However, CAR-T therapy is associated with a spectrum of immune-related toxicities…it has become apparent that rarely, CAR-T can cause gastrointestinal mucosal inflammation, termed immune effector cell-mediated enterocolitis (IEC-EC).”

Other treatments affecting the immune system can result in gastrointestinal inflammation. “Immune checkpoint inhibitors, including cytotoxic T lymphocyte associated anti-gen 4 (CTLA- 4) inhibitors, programmed death-1 (PD1) inhibitors, and PD-ligand 1 (PDL-1) inhibitors have been associated with colitis (with or without enteritis) in up to 54% of patients treated with these agents”

Key points:

  • “Occurring in up to approximately 6% of patients typically following B cell maturation antigen-targeted CAR-T therapy, IEC-EC presents with severe diarrhea and malabsorption, responds poorly to treatment, and portends a dire prognosis.”
  • “Step-up pharmacotherapy, often featuring biologics and small molecules drawn from the inflammatory bowel disease pharmacologic armamentarium.” Figure 6 presents an algorithm for evaluation and management.
  • “Patients typically present 1–3 months after CAR-T infusion with persistent watery, non-bloody diarrhea, often Grade 3 or higher [33]. Diarrhea is often severe and persistent, frequently accompanied by malnutrition and significant weight loss, and may necessitate prolonged parenteral nutritional support [25]. Diagnosis is often delayed due to the rarity and novelty of this condition, and the fact that patients receiving CAR-T have numerous other potential reasons to experience diarrhea.”

My take: There are a growing number of individuals needing CAR-T cell therapy. Recognizing this delayed complication quickly may help improve outcomes.

Related blog posts:

Puffins on the Edge of a Cliff Overlooking a Black Sand Beach

Federal Policies Changing Medical Standards

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BA Barsky et al. N Engl J Med 2026;395:419-421. Medical Standards by Federal Fiat

An excerpt:

“Historically, the federal–state division of authority over medical practice has been strict. This division is evident in health care financing and medical product regulation, for example. States license physicians and set standards for medical care, often incorporating standards established by the medical profession while allowing broad discretion for physician judgment.1…

The Trump administration has attempted to alter the balance of federal–state authority in the area of gender-affirming care in two important ways. First, in June 2025, the U.S. Department of Justice (DOJ) issued administrative subpoenas to more than 20 health systems and clinics providing gender-affirming care, demanding unusually broad information related to off-label prescribing of puberty blockers and hormones…The DOJ’s subpoenas, however, demanded information at the heart of physician judgment and the patient–doctor relationship, including physicians’ case-specific clinical assessments justifying off-label prescriptions and information that could be used to identify patients, including children, by name…

The second federal disruption came in December 2025, when Secretary of Health and Human Services Robert F. Kennedy, Jr., issued a declaration stating that gender-affirming care for children and adolescents is unsafe and does not meet professionally recognized standards of care…

Much of the authority and discretion now held by medical professionals and the states would move upward to a federal government that would exert expanded control over the health care that patients receive. Such a shift would potentially force all states to accept a single federal standard of care in various areas of medicine while concentrating immense medical power in the hands of political appointees. Federal authority over health care standards is appropriate in some instances. But this authority should be established using a proper legal process — Congress acting within its enumerated constitutional powers, or the executive branch acting under properly delegated authority — not by fiat.”

Established Roles for Setting the Medical Standard of Care
and Changes Implied by Trump Administration Actions.

My take: While this issue primarily affects a narrow area currently, it is not difficult to imagine that other administratioins could similarly impose policies affecting other sensitive decisions like abortion (expanding or limiting options), contraceptive availability, discussions about guns, and viability decisions.

Dr. Michael Wilsey: Endoscopy Pearls and Ergonomics (Part 2)

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Dr. Michael Wilsey gave our group an excellent update on Endoscopy Pearls and Ergonomics. My notes below may contain errors in transcription and in omission. Along with my notes, I have included many of his slides.

Yesterday’s post focused on endoscopy pearls. Today’s post focuses on ergonomics. Most of the attendees realized that we could use a lot of improvement in this area after listening to this presentation. This issue is likely of even greater importance in those with a high endoscopy case load.

  • A high percentage of gastroenterologists/pediatric gastroenterologists develop injuries related to repetitive endoscopy procedures.  These can be mitigated using proper ergonomics.  Although this advice is pretty straight forward, a lot of endoscopists could benefit from careful attention to this.
Areas included neck/upper back (44.0%), thumb (42.0%), hand/finger (38.0%), lower back (36.0%).
  • Keep Monitor near eye level and in front of you (don’t torque your neck)
  • Maintain good posture. Can start by standing upright against a wall
  • Position bed so elbows can be in a fairly neutral position with bed not more than 10 cm below elbows
  • Two-piece lead aprons helpful to distribute weight better
  • Handle endoscope more like holding a pencil than using a firm grip
  • Cushioned mat and cushioned soles can help with standing posture/fatigue