The role of normothermic perfusion In liver transplant (TRaNsIT Study): a systematic review of preliminary studies

Introduction: The success of liver transplantation has been limited by unavailability of suitable donor livers. The current organ preservation technique i.e static cold storage (SCS) is not suitable for marginal organs. Alternatively, normothermic machine perfusion (NMP) promises to recreate the physiological environment and thus provide better organ preservation. The objective of this systematic review, is to provide an overview on the safety, benefits and other potential useful parameters of NMP device. Material and Methods: We searched the current literature following registration in with the International Prospective Register of Systematic Reviews (PROSPERO) with registration number CRD42018086034 for prospective trials comparing the role of NMP device to SCS in liver transplant by searching the PubMed, EMBASE, Cochrane, BIOSIS, Crossref, Scopus databases and clinical trial registry. Results: The literature search identified five prospective clinical trials (four early phase single institutional and single randomized multi-institutional) comparing 187 donor liver on NMP device to 275 donor livers on SCS. The primary outcome of interest was to assess the safety and graft survival at day 30 after transplant following NMP of the donor liver. Secondary outcomes included were early allograft dysfunction (EAD) in the first seven days; serum measures of liver functions as (bilirubin, aspartate aminotransferase (AST), alanine amino transferase(ALT), alkaline phosphatase (ALP), international normalized ratio (INR) on days 1–7; major complications as defined by a Clavien-Dindo score ≥3; patient & graft survival and biliary complications at six months. The peaked median AST level between day 1-7 in the five trials was from 417-1252 U/L (range 84-15009 U/L) while on NMP and 839-1474 U/L (range 153-8786 U/L) in SCS group. The median bilirubin level on day 7 was ranged from 25-79 μmol/L (range 8-344 μmol/l) and 30- 47.53 μmol/l (range 9-340 μmol/l) in NMP and SCS groups respectively. There was no reported PNF in either groups in the three trials. There was inter trial variability in EAD which ranged from 15-56% in NMP group while 23-30 in SCS group. Biliary complications in form of 6 months’ biliary stricture were observed in NMP group ranged from 0-20%. None of the three trials reported any machine failure, although inadvertent events of catheter occlusion (four events) in hepatic vein and bile duct or unrecognized twist in portal vein (single event) were reported. Conclusion: This review outlines that NMP not only demonstrated safety and efficacy but also provides the favourable environment of organ preservation, repair, and viability assessment to donor liver with low rate of complication as PNF, EAD and biliary complication following transplantation, however further studies are needed to broaden our horizon