Use of Dual Hypothermic Oxygenated Machine Perfusion to Recover Extended Criteria Pediatric Liver Grafts

Abstract

The advent of machine perfusion is deeply changing the field of liver transplantation (LT), unveiling a spectrum of unexplored possibilities, both with hypothermic and normothermic perfusion. The renewed interest for these techniques originated from the necessity of improving preservation of grafts from extended criteria donors, which are now commonplace in everyday clinical practice. Hypothermic oxygenated machine perfusion (HOPE) has been associated with improved outcomes in grafts from donation after circulatory death (DCD) or grafts from extended criteria donation after brain death (DBD) donors. (1,2) As opposed to adult LT, the use of extended criteria donors seems much more limited in pediatric LT. Pediatric recipients are generally allocated whole grafts from pediatric donors or the left lateral segment resulting from the splitting of otherwise optimal grafts or living donation. In these scenarios, static cold storage generally allows satisfactory graft preservation.However, extended criteria donors are not exclusive of adult LT, and HOPE could also find specific indications in pediatric LT. Recently, the Groningen group (3) reported the successful transplantation of a graft from a pediatric DCD donor after dual hypothermic oxygenated machine perfusion (D-HOPE; ie, perfusion from both the portal vein and hepatic artery). During the procedure, the pressure settings were lowered as compared with those usually adopted in adults to avoid damaging the graft from excessive perfusion pressure, which has been observed in the experimental setting. (4) In this case, however, the graft weight was 1500 g, thus not representative of an average pediatric graft.After having gathered experience with D-HOPE for grafts from adult donors, (1) we recently applied this technique in 2 small-sized whole liver grafts from pediatric donors whose liver function tests were consistent with acute liver injury, confirming the safety and feasibility of D-HOPE also in the pediatric LT setting. Patient Presentation PAtient 1The donor was a drowned 13-year-old male with anoxic brain damage following 10 minutes of cardiac arrest and 40 minutes of unsuccessful resuscitation, who was admitted the day before he was declared brain dead. Height and weight were 170 cm and 65 kg, respectively. When he was proposed as a potential organ donor, liver function tests were consistent with acute liver injury: aspartate aminotransferase (AST), 966 IU/L (475 IU/L on admission); alanine aminotransferase (ALT), 504 IU/L (385 IU/L on admission); total bilirubin, 1.01 mg/dL (0.3 mg/dL on admission); and international normalized ratio (INR), 2.25 (1.53 on admission). Sodium level was 151 mg/dL. Blood pressure was maintained with 0.01 µg/kg/minute norepinephrine and 0.02 µg/kg/ minute epinephrine. The liver was accepted, but given Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; DBD, donation after brain death; DCD, donation after circulatory death; D-HOPE, dual hypothermic oxygenated machine perfusion; GRWR, graft-to-recipient weig...

Combined liver kidney transplantation for primary hyperoxaluria type 1: Will there still be a future? Current transplantation strategies and monocentric experience

“…A promising option, despite the limited experience in children, might be represented by ex vivo organ machine perfusion. 17,18 Thanks to machine perfusion, it is now possible to efficiently preserve a donated organ during complex surgical procedures, thus reducing the static cold ischemia time. 19,20 The possible advantages of delaying renal transplantation by 24-48 hours, when the liver graft should start functioning, thus preserving the kidney graft from excessive oxalate accumulation, 21,22 need to be evaluated.…”

“…New perspectives are now opening for PH1 treatment. A promising option, despite the limited experience in children, might be represented by ex vivo organ machine perfusion 17,18 . Thanks to machine perfusion, it is now possible to efficiently preserve a donated organ during complex surgical procedures, thus reducing the static cold ischemia time 19,20 .…”

“…In a median follow-up of 7 [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] years after transplantation, no child died and no liver graft failure was observed. Two kidney grafts (33%) were lost early after CLKT, the first due to primary nonfunction, possibly caused by the long ischemia time, the second one after 21 days due to early renal oxalate accumulation, despite a very aggressive HD protocol started immediately after transplantation.…”

“…Median [IQR] recipient's age at transplantation was 11 [1][2][3][4][5][6][7][8][9][10][11][12][13][14] years; in all cases, a compatible graft from a pediatric brain-dead donor aged 8 [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] years was used. In a median follow-up of 7 [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] years after combined liver-kidney transplantation, no child died and no liver graft failure was observed; three kidney grafts were lost, due to chronic rejection, primary non-function, and early renal oxalate accumulation. Liver and kidney graft survival remained stable at 1, 3, and 5 years, at 100% and 85%, respectively.…”

Not only a small liver - The pathologist’s perspective in the pediatric liver transplant setting

“…Nevertheless, limited evidence of machine perfusion implementation in the PLTx setting is available to date. The first report of a successful application of machine perfusion in the pediatric setting is dated 2019 and reported by Werner et al 46 , followed by the experience reported by the Turin group 47 . Indeed, PLTx requires a cautious approach, but once the benefits of machine perfusion will be ensured by multicenter studies, this technique would represent a valid support and eventually increase the PLTx donor pool.…”