How Low Can You Go with Split Livers?

Z Wang et al. Liver Transplantation 2023; 29: 58-66. Outcome of split-liver transplantation from pediatric donors weighing 25 kg or less

DJ Stoltz et al. Liver Transplantation 2023; 29: 3-4.(Editorial) Open Access! Exploring the lower weight limit of splitable liver grafts for pediatric recipients

From the editorial:

“In this issue of Liver Transplantation, Wang et al.7 describe the results of an innovative strategy to increase organ availability, particularly for low‐weight pediatric recipients, by utilizing a low‐weight donor population (≤25 kg) that historically has been avoided in pediatric split‐liver transplantation (SLT)…They found no significant differences in perioperative data, postoperative complications, patient survival, or graft survival between SLTs from donors ≤25 kg and the other three groups.”

Implications of study findings:

  • Splitting livers from donors weighing less than 25 kg will increase the pediatric donor pool and could improve waitlist mortality
  • Split smaller livers may mitigate “the clinical consequences of large‐for‐size syndrome and subsequent graft dysfunction”
  • “This approach requires a substantial level of surgical expertise to achieve comparable outcomes with more conventional operative techniques”
  • “1‐year graft survival for pediatric recipients receiving technical variant grafts was significantly worse at low‐volume centers performing an average of <5 pediatric liver transplantations per year” compared with high‐volume centers (89.9% vs. 95.3%; p < 0.001)
  • Limitations: Retrospective study. Also, only 22 of the split livers were from <25 kg donors

My take: Making the best use of this precious resource is a solemn responsibility. This study provides another reason for more transplants to be done in centers with a high level of expertise and more reasons to continue to use split livers. In those with sufficient expertise, even smaller livers can save two lives instead of one.

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Unfortunate or Unfair Disparities in Liver Transplantation

In medical school, I took additional courses in bioethics and one of the influential lecturers was Tristramm Engelhardt (Right to Health Care).  “According to him, injuries, disabilities, and diseases arising from natural causes are considered unfortunate. On the other hand, those situations become unfair when brought about by the doing of others. Engelhardt also notes that the result of someone’s unfair action should not be attributed to the society as a whole.”

Two recent articles detail the link between socioeconomics and outcomes in liver transplantation. Are these problems unfair or just unfortunate?

NH Ebel et al. Liver Transplantation 2022; 28: 1521-1529. A review of racial, socioeconomic, and geographic disparities in pediatric liver transplantation

Key points:

  • Disparities remain in pediatric liver transplantation at all time points: from access to referral for transplantation, likelihood of living donor transplantation, use of exception narratives, waitlist mortality, and inequitable posttransplant outcomes
  • Black children are less likely to be petitioned for exception scores, have higher waitlist mortality, are less likely to be the recipient of a living donor transplant, and have worse posttransplant outcomes compared with White children.
  • Children living in the most socioeconomically deprived neighborhoods have worse posttransplant outcomes.
  • Children living farther from a transplant center have higher waitlist mortality

KA Mohamed et al. Liver Transplantation 2022; 28: 1441-1453. Open access! Neighborhood poverty is associated with failure to be waitlisted and death during liver transplantation evaluation

Key points:

  • Based on retrospective analysis of 3454 patients (2011-2018), neighborhood poverty was independently associated with waitlisting (odds ratio 0.56, 95% confidence interval [CI] 0.38–0.82) and death during LT evaluation (hazard ratio 1.49, 95% CI 1.09–2.09)
  • Despite use of the objective prioritization with MELD scores in the allocation of organs, disparities in access for LT continues for vulnerable populations

My take: It is unfortunate but not surprising that poverty and socioeconomic factors adversely affect liver transplantation; the outcomes show stark differences. These issues, however, affect every aspect of health care (& beyond). Though they are not easily addressed, efforts to try to level the playing field are important especially with regard to transplantation to assure optimal use of this life-saving resource.

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Portage Pass Trail (near Whittier AK) with views of Portage glacier

Liver Transplant Outcomes in Children: Two Studies

Jean de Ville de Goyet et al. Hepatology 2022; 75: 634-645. European Liver Transplant Registry: Donor and transplant surgery aspects of 16,641 liver transplantations in children

This is an amazing study — “50-year period (1968–2017), clinical and laboratory data were collected from 133 transplant centers and analyzed retrospectively (16,641 liver transplants in 14,515 children).”

Key findings:

  • Overall, the 5-year graft survival rate has improved from 65% in group A (before 2000) to 75% in group B (2000-2009) (p < 0.0001) and to 79% in group C (since 2010) (B versus C, p < 0.0001).
  • Graft half-life was 31 years, overall; it was 41 years for children who survived the first year after transplant.
  •  The use of living donors steadily increased from A to C (A, n = 296 [7%]; B, n = 1131 [23%]; and C, n = 1985 [39%]; p = 0.0001)

My take: Liver transplantation provides a durable cure for most infants and children with severe liver disease.

A Shingina et al. Liver Transplantation 2022; 28: 437-453. Long-term Outcomes of Pediatric Living Versus Deceased Donor Liver Transplantation Recipients: A Systematic Review and Meta-analysis

Associated editorial: EM Dugan, AD Griesemer. Pediatric Living Donor Liver Transplantation: Optimizing Outcomes for Recipients, Donors, and the Waiting List

A total of 24 studies with 3677 patients who underwent living donor liver transplantation (LDLT) and 9098 patients who underwent deceased donor liver transplantation (DDLT) were included for analysis. Key findings:

Overall, this meta-analysis shows improved patient and graft survival at 1, 3, 5, and 10 years with LDLT compared to DDLT:

  • Patient survival: LDLT vs DDLT: 1-year (odds ratio [OR], 0.68), 3-year (OR, 0.73), 5-year (OR, 0.71), and 10-year (OR, 0.42)
  • Graft survival — LDLT vs DDLT: 1-year (OR, 0.50), 3-year (OR, 0.55), 5-year (OR, 0.5; 95), and 10-year (OR, 0.26)

While LDLT is often technically more challenging, it provides timely access (reducing wait-time deaths/deterioration) to a high-quality organ with minimal preservation time. In this cohort, LDLT patients had higher MELD and PELD scores at transplantation compared to the DDLT.

My take: Increasing use of LDLT, at centers with appropriate expertise, will lead to better outcomes in children with severe liver disease.

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Chattahoochee River in Sandy Springs, Ga

Food Allergy in Liver Transplant Recipients

F Mori et al. JPGN 2022; 74: 175-179. De Novo Food Allergy in Pediatric Recipients of Liver Transplant

This interesting review has several key points:

  • Reported prevalence of food allergy after liver transplant ranges from 5% to 40%
  • Younger age at transplantation is a risk factor for developing de novo post-transplant food allergy (dnPTFA)
  • Tacrolimus has been implicated as a risk factor for dnPTFA
  • Common dnPTFA are the same as in the general population: milk, egg, wheat, peanouts/nuts, fish, and soy

Management recommendations:

  • If the donor has a food allergy, the recipient should be tested within the first months of transplant for food-specific IgE and “it is advisable to introduce the suspected food in a controlled setting”
  • Elimination diet is mainstay of treatment. Some individuals may need modification of their immunosuppressive medications
  • Provide self-injectable epinephrine in those with food allergy
  • Monitoring of specific IgE/skin prick tests is advised

My take: There are increased allergy issues in kids who have had liver transplantation.

Related blog post: Lots of Allergy & Autoimmunity Issues Following Solid Organ Transplantation

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Equitable Access to Liver Transplant

R Rosenblatt et al. Hepatology 2021; 74: 2808-2812. Open Access. Equitable Access to Liver Transplant: Bridging the Gaps in the Social Determinants of Health

The problem:

“Evaluation for organ transplantation, a life-saving procedure, involves a multistep, highly selective process. Initially, referrals to appropriate subspecialists and a transplant center are required. During evaluation, candidates undergo formal assessment of adequate social support, psychological health, health insurance, adherence, and understanding of treatments. Each step in the transplant evaluation process is an opportunity for inequity to insert itself, resulting in disparate access to listing for transplantation. This manifests through mechanisms related to poor health literacy, lack of insurance or high copay, poor social support, and geographical location. Culture incapacity by health providers and implicit bias at the provider level and health care system level can create additional barriers. Examples of health inequities include lower referral rate for LT and inferior outcomes among Black and Latinx compared to White patients,(3) while, in addition to race/ethnicity, sex and health literacy(4) also strongly correlate with the likelihood of listing. SES [socioeconomic status] affects both waitlist mortality and post-LT survival as well.”

This article proposes policy measures to counter the deleterious effects of SDOH [social determinants of health]—identify and reduce implicit bias, expand and optimize telemedicine, and improve community outreach. “Structural racism, access to affordable insurance, health literacy, and substance abuse therapy are equally important factors that contribute to health disparities and inequities and warrant further commentary and research, but are outside the focus of this policy piece.”

Related blog post: Getting a Seat at the Liver Counter

Dietary Therapy for Adults with Crohn’s Disease

H Yanai et al. The Lancet 2021; The Crohn’s disease exclusion diet for induction and maintenance of remission in adults with mild-to-moderate Crohn’s disease (CDED-AD): an open-label, pilot, randomised trial

In this open-label trial of adults with mild-to-moderate biologic naive Crohn’s disease, key findings:

  • At week 6, 13 (68%) of 19 patients in the CDED plus partial enteral nutrition group and 12 (57%) of 21 patients in the CDED group had achieved clinical remission (p=0·4618)
  • Among the 25 patients in remission at week 6, 20 (80%) were in sustained remission at week 24 (12 patients in the CDED plus partial enteral nutrition group and eight in the CDED alone group)
  • 14 (35%) of 40 patients were in endoscopic remission at week 24 (eight patients in the CDED plus partial enteral nutrition group and six in the CDED alone group)

My take: Dietary therapy may be effective option for motivated adult patients with Crohn’s disease.

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Recurrent PSC in Children After Liver Transplantation

M Martinez et al. Hepatology 2021; 74: 2047-2057. Recurrence of Primary Sclerosing Cholangitis After Liver Transplant in Children: An International Observational Study

In this retrospective study, the authors examined recurrent PSC (rPSC) in children who had undergone liver transplantation (LT) with 3 yrs of median followup. Key findings:

  • rPSC occurred in 36 children, representing 10% and 27% of the subjects at 2 years and 5 years following LT, respectively
  • Subjects with rPSC were younger at LT (12.9 vs. 16.2 years), had faster progression from PSC diagnosis to LT (2.5 vs. 4.1 years), and had higher alanine aminotransferase (112 vs. 66 IU/L) at LT (all P < 0.01)
  • After LT, rPSC subjects had more episodes of biopsy-proved acute rejection (mean 3 vs. 1; P < 0.001), and higher prevalence of steroid-refractory rejection (41% vs. 20%; P = 0.04)

My take: rPSC, not surprisingly, was associated with a more agressive, immunoreactive phenotype prior to LT characterized by younger age, faster progression to end-stage liver disease, higher prevalence of IBD and more frequent/difficult allograft rejection

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Bahamas (courtesy of Mark Martin)

Anonymous Nondirected Liver Donors

D Yoeli et al. Liver Transplantation 2021; 27: 1392-1400. Challenging the Traditional Paradigm of Supply and Demand in Pediatric Liver Transplantation Through Nondirected Living Donation: A Case Series

This case series of 13 nondirected liver donors (ND-LLDs) (from 2012-2020) helps highlight this increasing trend of motivated donors who do not have a predetermined recipient. The Scientific Registry of Transplant Recipients documented 105 patients who underwent a living donor liver transplantation (LDLT) from ND-LLDs 2000-2019, with 39 in 2019 alone.

Key points:

  • While the article states that carefully selected ND-LLDs at high volume centers have excellent outcomes, the associated editorial (pg 1373-74) notes that there is a 0.2% living donor operative mortality. And, a significant number experience negative physical and socioeconomic effects of donation
  • The authors advocate more use of SPLIT livers to increase the donor pool (currently at 10 centers) to lower pediatric deaths on the waitlist
  • The authors note that the likelihood of receiving a LT is increased at high-volume pediatric centers (85%) compared to low-volume centers (41%). “Center expertise and volume is an important consideration…especially true for pediatric liver transplantation, which is relatively infrequent…551 [in 2019]” compared to 8345 adult liver transplants.

The commentary places some context regarding the donors.

  • 70% had previously donated a kidney (“Repetitive donor disorder?”)
  • Yet, “in some sense, nondirected donors may be the best qualified donors, as they are free of coercion”
  • The authors advocate for a “safe, well-informed” process and for national guidelines to address risks and the components of evaluation, medical and psychosocial

My take: It is amazing how much some individuals are willing to sacrifice to help others, especially in age when some react so harshly to being asked to consider the needs of their community.

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Hyde Farm, Marietta, GA

The Elephant in the Transplant Room: Personhood

A recent study and related editorial discuss the ethics and utilization of transplantation for children with intellectual disability.

In the study by Wightman et al, the researchers performed a retrospective cohort analysis of children receiving a first kidney, liver, or heart-alone transplant in the United Network for Organ Sharing dataset from 2008 to 2017. Key findings:

  • Definite intellectual disability accounted for 594 of 6747 (9%) first pediatric kidney-alone, 318 of 4566 (7%) first pediatric liver-alone, and 324 of 3722 (9%) first pediatric heart-alone transplant recipients. 
  • Children with intellectual disability account for 7%-9% of pediatric transplant recipients with comparable long-term outcomes to other pediatric recipients.
  • The article had a number of limitations including a lack of a standardized assessment of cognitive development.

In the editorial, the author “opposes the absolute exclusion of patients with intellectual disability and end-stage organ disease from transplantation waitlists provided that the candidates are expected to gain a predefined minimum benefit threshold of life-years and quality-adjusted-life years. Intellectual disability is one of many factors that should be considered in determining transplant eligibility and each candidate should have an individualized interdisciplinary assessment.”

In this commentary, it is noted that “the vast majority (85%) of individuals classified as having intellectual disability are able to live independently with minimum levels of support.” While the author would exclude those in a persistent vegetative state and those who were minimally conscious, otherwise he advocates “the candidate with intellectual disability should be given equal priority for organ transplantation.”

My view: The suitability for transplantation of individuals with intellectual disability centers on the issue of personhood; those who meet the threshold of personhood should be eligible to receive organ transplants without discrimination.  Wikipedia-Personhood: “Defining personhood is a controversial topic in philosophy and law and is closely tied with legal and political concepts of citizenship, equality, and liberty.”

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