How to Lower Pediatric Liver Transplantation Waitlist Mortality

From the editorial, Key Points:

  • Esmati et al.1 present a fascinating analysis of the impact on waitlist outcomes of a 2014 Eurotransplant (ET) policy that prioritizes patients younger than the age of 2 years with biliary atresia for deceased donor liver transplantation (DDLT) offers
  • Waitlist mortality decreased from 6.7% before to 2.3% after implementation of the new policy. Unexpectedly, this was not associated with an increase in DDLTs
  • During the same time period, the proportion of young patients with BA who underwent living donor liver transplantation (LDLT) increased from 55% to 74%.
  • Without adaptions to the pediatric Model for End‐Stage Liver Disease (MELD) or Pediatric End‐Stage Liver Disease scores, children can never fairly “compete” for deceased donor livers because of the tremendous volume and demand from the adult candidate list

My take (borrowed from editorial): There are many potential ways to achieve the desired goal of zero pediatric waitlist mortality. And, multiple strategies can successfully be pursued in parallel: prioritize children, increase use of LDLT, and increase/mandate use of split livers.

Related blog posts:

Another (unrelated) study in this issue -easy way to assess mobility (a key element of frailty) in adults with decompensated liver disease: AJ Groff et al. Liver Transplantation 29: 226-228. Open Access! A novel method using the level of mobility to predict mortality in patients admitted for decompensated cirrhosis: A prospective study The authors found the following: a value of <8 on The Johns Hopkins Highest Level of Mobility score (JH‐HLM, see below) was associated with much higher risk of mortality compared with those with a JH‐HLM score of 8.

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.

Related blog posts:

Chattahoochee River in Sandy Springs, Ga

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.

Related blog posts:

Hyde Farm, Marietta, GA

More on Time to Split (2018)

As noted in a blog last year (More on its Past Time to Split), increased use of split livers can reduce liver transplantation waitlist mortality in children.  Further justification for this approach is evident from a new study (DB Mogul et al. J Pediatr 2018; 196: 148-53, editorial pg 12) indicated that outcomes following split liver organs are equivalent to whole organ liver organs.

The authors examined two time periods: 2002-2009 and 2010-2015 using the Scientific Registry of Transplant Recipients. n=5715

Key findings:

  • 1-year survival from split liver transplant (SLT) improved during the later period compared to the initial period: 95% versus 89%. n=1626 (28.5% of all transplants)
  • 1-year survival from living donor liver transplant (LDLT) improved during the later period compared to the initial period: 98% versus 93%. n=661 (11.6% of all transplants)
  • 1-year survival from whole liver transplant (WLT) was essentially unchanged during the later period compared to the initial period: 95% versus 94%. n=3428 (60% of all transplants)

These data show that survival after transplant is no longer worsened by SLT and may be higher for LDLT than WLT.

The editorial by Dr. Bae Kim and Dr. Vakili note that there have been several proposals to encourage more use of SLTs.  One that was developed “would prioritize children <2 years old before local/regional adults except for those who were status 1 or who had a MELD score above 30.”  At this point, these efforts to favor SLT allocation have not been adopted by UNOS Board of Directors.

My take (borrowed from editorial): “The question should no longer be ‘To split or not to split?’ but rather ‘Why should we let children die when we can now split livers safely?'”

Related blog posts:

Chattahoochee River



Assessment of Organ Donation –MRI Often Precludes Need for a Liver Biopsy

A recent retrospective single-center study (J Satkunasingham et al. Liver Transplantation 2018; 24: 470-77) shows that MRI is a good tool to assess hepatic steatosis.  In total there were 144 liver donor candidates; a subset of 32 underwent liver biopsy.

When examining magnetic resonance spectroscopy (MRS) and MRI -proton pump density fat fraction (PDFF), the authors found that MRS-PDFF and MRI-PDFF had 95% and 100% negative predictive value in identifying patients with clinically  significant histologic steatosis (≥10%).

The associated editorial by James Trotter (pg 457-58) makes several important points:

  • Currently living donor transplantation in the U.S. accounts for 4% of all transplants
  • In his center (and most centers), protocol biopsy are not required prior to liver donation.  The main indications for donor liver biopsy are biochemical dysfunction or steatosis on imaging studies.

My take (borrowed from editorial): “Noninvasive estimation of hepatic steatosis is sufficiently accurate to forgo liver biopsy in most donors, although ultimately this decision will continue to rest with the individual center.”


First-Hand Account: Living-Donor Liver Transplantation

From NY Times: Donating an Organ to My Son

An excerpt:

It has been a year and half since the surgery. Sammy looks great and is on minimal medication. He goes to school full time, and most people have no idea what he went through. The scar on his abdomen has mostly faded, and we aren’t sure if he even has any memories of this experience.

My liver has grown to full size and my scars are nearly invisible. But that doesn’t mean I am entirely recovered. There are moments, and they are less frequent and further between, that I get spontaneously choked up. This experience was both frightening and inspiring. I had to briefly give up being both doctor and a mother to become a patient. It was as a living donor that I was able to help my son the most.

Another comic account of living liver donation:

Chattahoochee River

Chattahoochee River

Living Liver Donors: 97% Would Do It Again

A recent study (VR Humphreville et al. Liver Transpl 2016; 22: 53-62) indicates that living liver donors report a high satisfaction following donation.

The authors examined a cohort of 127 living liver donors from the University of Minnesota; donation had occurred between 2 years and 16 years previously.  In addition to a donor-specific survey (DSS) completed by 107, the participants completed the short-form 36 health survey to assess health-related quality of life.

Key findings:

  • Almost all donors reported that they would donate again (97.2%)
  • Satisfaction rate correlated with the outcome of the liver transplant recipient along with pain after donation and vitality after donation. 91.6% rated their satisfaction with the donation process as >8 on a 10 -point scale, with 10 being “extremely satisfied”
  • Health-related quality of life was higher among donors than the general population (though they likely had higher scores than the general population at baseline)

The study elaborates on the potential complications with the most frequent  being incisional discomfort in 34%.

My Take: this information on high satisfaction will be useful for transplant programs and those considering living liver donation.