This study used multicenter data from the Society of Pediatric Liver Transplantation on first-time pediatric (aged <18 years) liver transplant recipients (n = 3801) in the US and Canada (1995-2016).
7.4% developed HAT within the first 90 days of transplantation.
Of those who were retransplanted, 20.7% developed recurrent HAT.
Those less than 1 year had the highest risk OR 1.20).
Lower Risk for HAT:
Recipients with split, reduced, or living donor grafts had decreased odds of HAT (OR, 0.59; P < .001 compared with whole grafts)
Adolescents aged 11-17 years (OR, 0.53; P = .03).
HAT increased risk of graft failure and mortality:
Fifty percent of children who developed HAT developed graft failure within the first 90 days of transplantation (adjusted hazard ratio, 11.87; 95% CI, 9.02-15.62)
Mortality risk (w/in 90 days after transplantation): adjusted hazard ratio, 6.18 (95% CI, 4.01-9.53).
The finding that split grafts had lower rates of HAT may be related to the fact that these grafts more typically come from larger donors with larger vessels. Historically, split grafts had been described as a risk factor for HAT. The authors note that high-performing centers with the lowest incidence of HAT “also tend to have high rates of living and split transplants, suggesting that surgical expertise may play a role in the decreased risk of HAT in select recipients with technical variant grafts.”
Increased rates of HAT among those who were retransplanted, in some, could be related to thrombophilic conditions; thus, consideration of anticoagulation protocol could be needed
My take: Continued efforts are needed to reduce HAT due to its impact on liver transplantation outcomes. One of the biggest risk factors is age. While this would seem to be a nonmodifiable factor, improving recognition and treatment of biliary atresia could help.
Below I’ve included a few slides and some notes from recent Aspen Webinars; my notes may have errors of omission or transcription.
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
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.
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.
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.
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.
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.
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.
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).
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.
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.
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.
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)
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.
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.
“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.
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.
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.