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Page 6 of 17 Calinescu et al. Hepatoma Res 2021;7:59 https://dx.doi.org/10.20517/2394-5079.2021.26

[56]
Overall, morbidity associated to LT might be as high as 67% , with infection being the first cause. This risk
may be increased in patients who are exposed to both immunosuppression and chemotherapy; in a
monocentric report, infection was identified as the most common morbidity and reached a level of 36%
[57]
(cholangitis, bacteremia, central line infections, abdominal collections, and pneumonia) . Vascular
complications are the second most frequent cause of problems after LT and seem to be higher in patients
transplanted for malignancies. Hepatic artery thrombosis is reported to be as high as 28% [4,11,58] . Although
some groups do not mention a higher thrombosis risk after LT for HBL patients , this might be because
[59]
these patients do not have liver dysfunction, portal hypertension, or hyper splenism and their coagulation
profile is normal at LT, with a possible increased procoagulant activity due to cisplatin. This might justify
the systematic use of antithrombotic and/or anticoagulant strategy after LT for HBL .
[11]

Biliary complications might occur in up to 40% of the cases, as in other indications for LT [60,61] . In a 19-
patient series, one patient (5%) developed a bile duct stricture treated with percutaneous transhepatic
[50]
cholangioplasty and one bile leak (5%) was treated by percutaneous drainage . Faraj et al. described an
[59]
incidence of 8% biliary complications: two bile leaks, one needing a percutaneous drainage and the other
laparotomy and drainage. The Japanese national cohort of living donor LT for HBL showed overall 47.2%
surgical complications: 21.7% biliary complications for the hepaticojejunostomy subgroup and 31.3% for the
duct-to-duct anastomosis subgroup .
[62]
Other complications such as small bowel obstruction and chylous ascites resolving spontaneously were
[59]
[59]
described more rarely.

Rejection-free survival in HBL recipients with living related donor grafts was 91% compared to 58% in
controls; it is thought that less immunosuppression is required after LT for hepatoblastoma as a result of
diminished immunity after neoadjuvant chemotherapy [3,33,53,58] . The findings of rejection rates seem different
in the case of deceased donation with 50% and 70% in two series with 8 and 10 patients, respectively [60,63] . A
larger study confirmed the difference in rejection rates with 50% rejection in HBL patients vs. 75% in a
matched biliary atresia LT patient cohort . Furthermore, decreased rejection rates persist many months
[52]
after completion of chemotherapy, probably suggesting an immunomodulatory effect other than just
[58]
immunosuppression . Together with the altered renal function, the decreased rejection rates suggest a
need for immunosuppression modulation after LT for HBL.

[60]
Post-transplant lymphoproliferative disease was reported in 10% of patients . Nevertheless, none of them
died in a United Network Organ Sharing (UNOS) database inquiry .
[64]
Retransplantation was reported to occur in 10% of the patients after LT for HBL, because of vascular
thrombosis (60.6%), primary non-function (15.2%), and rejection (9.1%) [11,60] .

Survival after liver transplantation for hepatoblastoma
Historically, patients with advanced and metastatic HBL had a 5-year survival of 69%, as reported in
[65]
2006 . Almost 10 years later, improved chemotherapy and aggressive transplant listing upgraded 10-year
patient survival to 84% [4,21] . A retrospective UNOS analysis identified an overall survival of 76% with a graft
[8]
survival of 77%. The three-year overall patient and graft survival was of 85% starting with 2009 . These
results are in line with the SIOPEL 3 and 4 trials that found a 75% overall survival for patients with
unresectable HBL [22,66] [Table 1].