Tag Archives: liver transplantation survival

Costs and Opportunity Costs in Pediatric Liver Transplantation

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GV Mazariegos et al. Liver Transplantation 2023; 29: 671-682. Open access! Center use of technical variant grafts varies widely and impacts pediatric liver transplant waitlist and recipient outcomes in the United States

Background: Waitlist (WL) mortality is highest in children under the age of 1 year (12.5 deaths/100 WL years).2 It is thought that TVG (technical variant grafts) [including living donor (LD) and deceased donor split/partial grafts] improve outcomes.

Methods: The authors, in this retrospective study, analyzed Organ Procurement and Transplantation Network (OPTN) data on first-time LT or liver-kidney pediatric candidates listed at centers that performed >10 LTs during the study period, 2004–2020. 

Key findings:

  • Sixty-four centers performed 7842 LTs; 657 children died on the WL
  • Death from listing was significantly lower with increased center TVG usage (HR = 0.611) and LT volume (HR = 0.995)
  • Recipients of LD transplants (HR = 0.637) had significantly increased survival from transplant compared with other graft types, and recipients of deceased donor TVGs (HR = 1.066) had statistically similar outcomes compared with whole graft recipients

My take (borrowed from authors): “LD partial grafts and overall volume performed by the center in the preceding 3 years was significantly associated with increased post-LT survival. Deceased donor graft type (DD TVG vs. DD Whole) was not a predictor of post-LT survival after accounting for patient diagnosis, center volume, and other significant factors that were predictive of survival. DD TVG should not be considered an inferior graft option in experienced centers…LD grafts are associated with a survival advantage.”

BA Sayed, M Cattral, VL Ng. Liver Transplantation 2023; 29: 663-664. Open access! (editorial) Insufficient use of technical variant grafts: An unfulfilled promise in pediatric liver transplantation Key points:

  • “While outcomes have improved, with current 1- and 5-year patient survival >97% and 94%, respectively, many children continue to die on the waitlist (WL) or are removed because they are too sick.1,2“
  • “As expected, these children were younger, smaller, sicker (more status 1 listings), and remained on the WL longer than children who received a transplant during the same time period…These small infants are particularly at risk because of the difficulty of obtaining an appropriately sized-matched graft. Data indicate that this problem can be solved largely by increasing the use of technical variant grafts (TVGs), which includes living donor (LD) grafts and split/reduced grafts from deceased donors (DDs).4,5“
  • “This manuscript obliquely touches on another pressing issue within the pediatric LT community, namely, the core skill set of a pediatric LT surgeon. Currently, there is no such distinct designation in the North American training environment, and therefore, no training requirements exist. To provide the full spectrum of surgical care, the technical skill set should include LD hepatectomies and graft implantations, DD graft reduction/splitting, the reduction or hyper-reduction of left lateral segment grafts, and staged abdominal closure.”

My take: Where a patient is listed is a very important variable in outcomes. Choosing a low volume center without availability to perform TVG increases the risk of lethal outcomes. This information should be disclosed to families at all centers.

Also: T Miloh et al. Liver Transplantation 2023; 29: 735-744. Open access! Costs of pediatric liver transplantation among commercially insured and Medicaid-insured patients with cholestasis in the US

Health care resource utilization and costs associated with pediatric LT were retrospectively assessed using insurance claims data from the US IBM MarketScan Commercial and Medicaid databases collected between October 2015 and December 2019. Study cohort: 53 commercially insured and 100 Medicaid-insured children

  • Key findings: Commercially insured and Medicaid-insured patients averaged US $512,124 and $211,863 in medical costs and $26,998 and $15,704 in pharmacy costs, respectively

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Liver Shorts: Autoimmune Liver Disease/HLA profiles, Saroglitazar for fatty liver, and Liver Transplantation Survivorship

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Y Ma et al. Hepatology 2021; 74: 2032-2046. Open Access: Human Leukocyte Antigen Profile Predicts Severity of Autoimmune Liver Disease in Children of European Ancestry

The main reason I had to highlight this article is the study period was 42 years!!! (1977-2019, n=236 children). Key findings: “Unique HLA profiles are seen in each subgroup of juvenile AILD:  DRB1*03 for AIH-1, DRB1*03 plus DRB1*07 for AIH-2, and DRB1*13 for ASC. DRB1*03 and the A1-B8-DR3 haplotype are disease-predisposing genes for all three subgroups. The influence of HLA class II genes on disease severity is strong, DRB1*03 homozygosity and possession of DRB1*13 being associated to histologically more advanced disease from onset, while DRB1*07 is linked to the least optimal response to immunosuppression”

S Gawrieh et al. Hepatology 2021; 74 1809-1824. Saroglitazar, a PPAR-α/γ Agonist, for Treatment of NAFLD: A Randomized Controlled Double-Blind Phase 2 Trial

The “EVIDENCES IV study was a multicenter, randomized, double-blind, placebo-controlled phase 2 study to evaluate the safety and efficacy of saroglitazar.” n=106. Key findings:

  • For ALT: mean percent change from baseline at week 16 was −25.5% (5.8), −27.7% (5.9), and −45.8% (5.7), with saroglitazar 1 mg, 2 mg, and 4 mg, respectively, versus 3.4% (5.6) in placebo (P < 0.001 for all)
  • Compared with placebo, saroglitazar 4 mg improved liver fat content on MRI PDFF (4.1% [5.9] vs. −19.7% [5.6]), adiponectin (−0.3 μg/mL [0.3] vs. 1.3 μg/mL [0.3]), homeostatic model assessment–insulin resistance (−1.3 [1.8] vs. −6.3 [1.7]), and triglycerides (−5.3 mg/dL [10.7] vs. −68.7 mg/dL [10.3]) (P < 0.05 for all)
  • Saroglitazar was well-tolerated. A mean weight gain of 1.5 kg was observed with saroglitazar 4 mg versus 0.3 kg with placebo (P = 0.27)

My take: This study shows the potential of one agent for pharmacologic therapy for NAFLD/MAFLD.

SR Lieber et al. Liver Transplantation 2021; 27: 1454-1467. What Survivorship Means to Liver Transplant Recipients: Qualitative Groundwork for a Survivorship Conceptual Model

“A majority of LT recipients (75%) identified themselves as survivors. Integral to the definition of survivorship was overcoming hardship (including experiences on the waiting list) and the unique experience of being given a “second chance” at life. Motivations to survive included a new chance at life (55%), family (40%), spirituality/faith (30%), and fear of rejection (15%)”

High Survival Rates for Biliary Atresia Patients Needing Liver Transplantation

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A recent retrospective study (SA Taylor et al. J Pediatr 2020; 219; 89-97) examined patients enrolled in the Society of Pediatric Liver Transplantation (SPLIT) registry, including 547 before 2002 and 1477 after 2002.

Key findings:

  • Before 2002, patient and graft survival were 81% and 90%.
  • After 2002, patient and graft survival were 90% and 97%. This improvement is perhaps more impressive as there was evidence of increased disease severity at time of transplantation in the later cohort.
  • The reasons for these improved outcomes include reduced relisting for transplant, less rejection, less culture-proven infection, fewer reoperations, and less vascular complications (eg. hepatic artery thrombosis and portal vein thrombosis).
  • Donor age (0-5 months) was a risk factor for graft loss; compared to 1-17 years, the hazard ratio was 5.525.  However, in the later group, recipient age of ≤11 months was no longer a risk factor for patient death.
  • Bacterial infection or sepsis remain the leading cause of death after transplantation.

Due to improvement in survival, the authors note that some have advocated for primary liver transplantation instead of Kasai portoenterostomy.  “A report of 626 patients with biliary atresia, of whom 50% underwent primary liver transplantation without Kasai portoenterostomy, demonstrated improved survival.” (JAMA Surg 2019; 154: 26-32)

My take: This information about survival is certainly encouraging –though many challenges remain, especially to improve comorbidities.

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Projected 20-Year and 30-Year Survival Rates for Pediatric Liver Transplant Recipients (U.S.)

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A recent study (MG Bowring et al. JPGN 2020; 70: 356-63) provides data on pediatric liver transplantation (LT) survival rates and projected survival rates.

This retrospective cohort study included 13,442 first-time pediatric (<18) LT recipients from 1987-2018.

Key findings:

  • Projected 20-year survival rate for pediatric LT from 2007-18: 84.0%
  • Prior 20-year survival rates: 72.8% (1997-2006 cohort) and 63.6% (1987-1996 cohort)
  • Projected 30-year survival rates for pediatric LT from 2007-18: 80.1%
  • Prior 30-year survival rates: 68.6% (1997-2006 cohort) and 57.5% (1987-1996 cohort)
  • Projected outcomes with split LT (28% of 2007-2018 cohort) are similar to outcomes with whole LT

My take: While projections can overestimate and underestimate survival rates, the clear trend has been a remarkable improvement in long-term outcomes.  This published data can provide current expectations when counseling families, though with ongoing improvements in management/development of tolerance, the hope is for even better outcomes.

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Weak Link in Liver Transplantation Survival

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A recent article and editorial (DH Leung et al. Liver Transpl 2016; 22: 1584-92 & editorial by JC Bucuvalas, S Feng 1466-68) provides a better picture of long-term survival for pediatric patients facing the prospect of liver transplantation.

Among patients less than 2 years in the UNOS data sharing registry, there were 994 with biliary atresia (BA) and 221 with other chronic liver disease.

The key data:

  • The overall postlisting mortality was 19.6% with most of this due to wait-list mortality (12.4%).  Posttransplant mortality was 8%.
  • The non-BA patients had a higher wait-list mortality compared with BA patients: 23.9% vs 9.8%
  • Risk factors for mortality included lack of exception points (HR 5.8), and initial creatinine >0.5.  In addition, BA patients without prior abdominal surgery (eg Kasai) was higher (risk was 1.6 times greater) than in those with BA with presumed Kasai.

Reviewing the article, it is not clear to me if patients removed the waitlist (eg due to sepsis and other causes) are included in this analysis.  Thus, the true postlisting mortality may be higher than 20% if all needy individuals are considered.

From the editorial -other aspects:

  • Only one-third of pediatric recipients have optimal outcomes which would include normal LFTs, maintained on monotherapy immunosuppression, normal growth, and free of comorbidity.  In addition, even among those with ‘optimal’ outcomes, many would still have histologic injury.
  • The “incidence of nonstandard exception requests has increased 5-fold and is now used on behalf of 44% of wait-listed children.”  Importantly, children with public insurance were less likely to have petitions for exception PELD points.

My take (with help from editorial): To improve outcomes, this means starting with candidate selection and working on each step: traversing wait-list management and optimizing posttransplant care.

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