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.

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.

Related blog posts:

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



Picking winners and losers with liver transplantation allocation

From a pediatric hepatology viewpoint, I’ve always been concerned that scoring systems  do not favor children.  More data is now available relevant to this topic:

  • Goldberg et al. Liver Transplantation 2012; 18: 434-43, editorial: 381-83 
  • Sepulveda et al. Liver Transplantation 2012; 18: 413-422, editorial: 389-90

These articles and the editorials look at the model for end-stage liver disease (MELD) and exceptions for hepatocellular carcinoma (HCC) as well as the issue of split livers to expand the donor pool.

The goals of liver transplantation allocation is to distribute livers to  minimize waiting list mortality, to distribute this valuable resource fairly, and to improve long-term outcomes.  How are we doing?

With regard to HCC, the authors indicate that the current policy is increasing the number of individuals transplanted with this indication.  Before MELD, 4.6% of all transplants were for candidates with HCC.  Between 2002-2007, the number increased to 26%.  This has dramatically improved the outcomes in this previously almost universally fatal disease.

But is the priority afforded by MELD priority unfair?  From 2005-2009, Goldberg et al show that the rate of individuals with HCC removed from the waiting list because of death or disease progression was much lower than non-HCC patients: 4.2% vs. 11% (90-day waitlist outcome).  Patients with HCC with exception points were 2.62 times less likely to die by waiting.  Thus, the authors conclude that allocating 22 MELD points to HCC patients greatly overestimates 90-day mortality.  Other conditions that receive 22 MELD points include candidates with hepatopulmonary syndrome, cholangiocarcinoma, cystic fibrosis, familial amyloidotic polyneuropathy, and portopulmonary syndrome.

Sepulveda et al performed a retrospective review of the experience from split liver transplantation in French adults.  In their cohort of 36 patients who received extended right grafts from split livers, there were increased complications.  Only 21 patients had a relatively easy postoperative course.  Six patients required retransplantation.  Overall survival rate was 84.2% and 77.7% at 1 and 5 years.  Complications were related to ischemia of hepatic segment 4.

In the editorial, Riccardo Superina makes several important points:

  • Many centers have equivalent outcomes for whole and split livers; there is likely a learning curve to improve technique.
  • In the U.S., between 2002-2009, only 288 split livers grafts were performed in adults whereas there were >29,000 whole liver transplants performed.
  • In the U.S. children have the highest mortality rates on the waiting list.  In 2008, 18% of children died without a chance for liver transplantation.
  • In France, allocation policy dictates that livers from all donors less than 30 years old should be directed to children first with the stipulation of liver splitting.  If this policy were adopted in US, it could alleviate the organ shortage for children who are currently most disadvantaged by UNOS (United Network for Organ Sharing) allocation policy.

Related blog posts:

Big gift, how much risk

Sarcopenia, fatigue, and nutrition in chronic liver disease

A liver disease tsunami

Additional references:

  • -Am J Transplant 2010; 10: 1643-48.  HCC patients advantaged with current allocation
  • -Clin Gastro & Hep 2008; 6: 1255. solutble TNF receptor 75 better at predicting mortality risk than MELD>
  • -Gastroenterology 2008; 135: 1568. MELD has changed allocation -less-ill patients now getting higher risk organs.
  • -Liver Transplantation 2006; 12: S128-S136. Guidelines for exceptions (increased status)
  • -Liver Transplantation 2006; 12: 12-15, 40-45. 53% of pediatric livers allocated based on other factors (eg. exception, status 1) than PELD score
  • -Gastroenterology 2003;124: 91-96, 251. MELD scores works fairly well in adults; factors in bilirubin, INR, creatinine.