Online Aspen Webinar (Part 7) -Liver Organ Allocation

Below I’ve included a few slides and some notes from recent Aspen Webinars; my notes may have errors of omission or transcription.

Key Points:

  • The new allocation policy tries to make liver organ allocation more equitable in terms of disease acuity at time of transplantation and access to allografts
  • The changes, based on some preliminary data, appear to improve the likelihood of children receiving needed organs. Dr. Bondoc specifically cited the work of Dr. John Bucuvalas in pointing out some of the systemic ways that the previous system disadvantaged children.
    • Infants are at the greatest risk on the wait list.  Yet, successful transplantation in children could be beneficial for many decades
    • PELD underestimates mortality risk
    • 25% of pediatric donors have historically gone to adults

 

Related blog posts:

More School Advice for Organ Transplant Recipients, Plus Another Benefit of the Influenza Vaccine

Link to PDF (from Pediatric Infectious Disease Society:

FAQs Regarding Return to School for Children after Solid Organ Transplant in the United States During the COVID-19 Pandemic

Some excerpts:

Are pediatric SOT recipients at higher risk for getting COVID-19 compared with other children?
Children of any age can get COVID-19, but they seem to have milder disease than adults. Pediatric SOT recipients do not seem to get COVID-19 more often than other children.

If infected with COVID-19, are pediatric SOT recipients at higher risk for developing severe disease or complications?

Based on experience with other viruses, and from reports of COVID-19 in adult SOT patients, there are a few things that may increase the risk of severe COVID-19. These include:
1) Having undergone transplantation in the last 3-6 months
2) Receiving high doses of immunosuppression (such as for treatment of rejection)
3) Having other medical problems such as diabetes, obesity, or certain lung conditions (refer to CDC website under Helpful Resources for more details)
It is not known if the above factors also put children with SOT at risk. In fact, of all the reports among pediatric SOT recipients with COVID-19 published so far, the majority have had mild symptoms and recovered.

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Surprised This Was Published: Liver Transplantation in Undocumented Immigrants

I was keenly interested in a recent study: BP Lee, NA. Terrault. Liver Transplantation in Unauthorized Immigrants in the United States. Hepatology 2020; 71: 1802-12.  Given the potential for causing a political firestorm, I was surprised it was published.

Definitions: “Unauthorized immigrants, also termed illegal aliens in US federal statures are…all foreign-born non-citizens who are not legal residents.”  Since March 2012, UNOS has required transplant centers to record citizenship…”primarily to better understand transplant tourism.” The authors excluded international transplant tourists in their cohort.

Key findings: 

  • 116 of 43,192 (0.4%) liver transplant (LT) recipients were unauthorized immigrants
  • The majority were from Mexico (52%).  Others came from Guatemala (7%), China (6%), El Salvador (5%) and India (5%).
  • Unauthorized immigrant recipients had a similar risk of graft failure (sHR 0.74) and death (sHR 0.68), though at time of LT, there was higher disease severity (higher MELD scores and increased need for renal replacement therapy).
  • Most LTs for unauthorized immigrants took place in California (47%) and New York (18%).  Texas (3%) and Florida (4%) had a lower proportion of LTs for unauthorized immigrants based on population distribution.
  • The authors note that unauthorized immigrants are different that transplant tourists  –they pay social security tax/other taxes and contribute to organ donation (~3% of donated organs) whereas transplant tourists do not.
  • The authors note that unauthorized immigrant LTs were less than half the number of transplant tourist LTs; the later LT recipients are commonly individuals from Persian Gulf countries.
  • Current federal law mandates that LT be distributed based on “established medical criteria” which does not suggest a “tiered allocation system by citizenship.”  Almost half of the unauthorized immigrant LTs were covered by Medicaid.

My take: Unauthorized immigrants are underrepresented as LT recipients compared to their total population distribution in the U.S.  This likely is due to a number of barriers.  Interestingly, this population is not underrepresented when it comes to organ donation.

 

High Survival Rates for Biliary Atresia Patients Needing Liver Transplantation

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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Island Ford Nat’l Recreational Area, Sandy Springs

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

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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View from the top of Blood Mountain, Ga

What to Expect After Pediatric Liver Transplantation: Cognitive Function and Quality of Life

A recent study (D Ohnemus et al. Liver Transplantation 2020; 26: 45-56, editorial 9-11) examined health-related quality of life (HRQOL) and cognitive functioning approximately 15 years after liver transplantation (LT).

Study details:

Median age 16 years.  Original group was a SPLIT research cohort recruited from 20 centers and then tested at multiple time points; for this study, 8 sites of the original 20 were included.  It is noted that patients with serious neurologic injury were excluded. Among an initial group of 108, there were 79 available for potential enrollment.  In this group, 65 parent surveys were completed and 61 child surveys.

Key findings:

  • For cognitive and school functioning, 60% and 51% of parents reported “poor” functioning, respectively (>1 SD below the health mean).  41% of children rated their cognitive function as poor.
  • Adolescents’ self-reported overall HRQOL was similar to that of healthy children; in contrast, parents rated their teenage children as having significantly worse HRQOL than healthy children in all domains.
  • The cognitive score in the poor functioning group at the latest time point was lower than at first time point measurement (ages 5-6 years and at least 2 years after LT), “suggesting that difficulties intensified in adolescence for those who have problems in early childhood.”
  • Almost half had received special educational services.

The editorial notes that the PedsQL Cognitive Functioning Scale scores used by the investigators were considered subjective.  “The more objective PedsPCF scores fell within the normal range.”

My take: This report indicates that a majority of children are likely to have some cognitive deficits and many are likely to have reduced HRQOL following liver transplantation; in addition, if these problems are detected at a younger age, they are likely to persist.

Related blog posts:

 

Mural on Atlanta’s Beltway

Outcomes of Liver Transplantation in Small Infants

A recent study (H Yamamoto et al. Liver Transplantation 2019; 25: 1561-70) provides data on the outcomes of infants who underwent liver transplantation (LT) in the United Kingdom (King’s College Hospital).

A total of 64 infants underwent LT (1989-2014) at a single institution. The authors compared “extra-small” (XS) infants in the first 3 months of life to “small” (S) who were 3-6 months of age.

Key findings:

  • Acute liver failure was the main indication for LT in the XS group (n=31, 84%) compared to the S group (7, 26%)
  • Hepatic artery thrombosis and portal vein thrombosis were similar in both groups: 5.4% and 10.8% in the XS and 7.4% and 11.1% in the S group
  • Bilary stricture and leakage were similar: 5.4% and 2.7% in the XS and 3.7% and 3.7% in the S group
  • 1-, 5-, and 10-year survivals were 70.3%, 70.3% and 70.3% in the XS group and 92.6%, 88.9%, and 88.9% in the S group (not statistically significant)

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Quebec City, Frontenac Hotel and Boardwalk (early in the day)

Need Liver, Will Travel (2019)

A recent study (AJ Kwong et al Clin Gastroenterol Hepatol 2019; 17: 2347-55) quantifies the potential advantage of moving to receive a liver transplant. This had been discussed in 2016 blog post as well (Need Liver, Will Travel)

During the study period (2004-2016), there were 104,914 waitlist registrations.

Key findings:

  • 60.985 patients received a liver transplant during the study period
  • 2930  (2.8%) pursued listing at a distant center
  • Distant listing was associated with a 22% reductinon in the risk of death within 1 year

My take: this study highlights socioeconomic disparity in acquiring a liver transplant along with potential geographic disparities.

Related article:

“Transplantation Traffic –Geography as Destiny for Transplant Candidates” NEJM 2014; 271: 2450-52.  Describes ongoing geographic inequality in organ distribution and obstacles to improving allocation.

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Botanical Garden,, Chicago

Sad Truth: Job Security in Hepatology

A recent study (ND Parikh et al. Hepatology 2019; 70: 487-95, and associated editorial JA Marrero. 459-61) provide a forecast of increasing liver disease and liver disease severity, driven mainly by fatty liver disease and obesity.

Key findings:

  • Nonalcoholic fatty liver disease (NAFLD) related additions to the liver transplant waitlist expanded from 391 in 2000 to 1605 in 2014.  This corresponded to an overall increase in obesity of 44.1% during that time period.
  • NAFLD-related wait-list additions were predicted by the prevalence of obesity 9 years prior.
  • The authors anticipate that obesity population will increase to over 92 million adults by 2025.
  • The authors project that NAFLD-related wait-list additions will increase to 2104 by 2030, a 55% increase

Because the decrease in complications related to new treatments for Hepatitis C is not expected “until well into the next decade,” the burden of chronic liver disease will continue to rise.

The editorial notes that overall graft survival rates for obese patients with BMI less than 40 do not appear different than those of lean individuals.  Those with BMI >40 had reduced 5-year graft and survival rates.  Also, obese patients have higher morbidities, even in those without reduced survival.

My take: This study identifies a marked increase in end-stage liver disease in the growing population of obese patients.

Related blog posts:

How Does USA Compare to Other Countries in Pediatric Liver Transplantation

A recent study (B Fischler et al. JPGN 2019; 68: 700-05) compared the similarities and differences in allocation experience among 15 countries based on a survey completed by a representative hepatologist in each country.

Key findings:

  • The number of liver transplants was 4 to 9 million inhabitants younger than 18 years for 13 of the 15 respondents. USA had the 5th highest rate at ~7 per million inhabitants (Figure 2)
  • USA had the 3rd highest donation rate per million inhabitants, ~26 per million.  Spain had highest rate at 35 per million.  This is partly related to Spain allocating all nonugent pediatric cadaveric donors to pediatric candidates.
  • USA had the 3rd lowest rate of living-related liver transplantation percentage in children < 2 yrs, approximately 10%.  Both Turkey and Poland had rates near 90%.
  • USA had one of the lowest rates of %split liver transplantations for children <2 yrs, less than 10%. Italy, Netherlands, and New Zealand had rates near 90%.
  • USA had the 4th highest waitlist mortality for children <2 yrs, approximately 11%

My take: This study indicates that the rate of split liver transplants and living related liver transplants are much lower in USA than in other countries.  This is likely to reduce donor pool and contribute to increased waiting list mortality.

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