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Introduction The success of liver transplantation has been limited by the 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 hence holds promise for the better organ preservation. The objective of this systematic review is to provide an overview of the safety, benefits, and insight into the other potential useful parameters of NMP in the liver preservation. Material and Methods We searched the current literature following registration in 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, and Scopus databases and clinical trial registry. Results The literature search identified five prospective clinical trials (four being early phase single institutional and single randomized multi-institutional) comparing 187 donor livers on NMP device to 273 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), and international normalized ratio (INR) on days 1–7; major complications as defined by a Clavien-Dindo score ≥ 3; and patient and graft survival and biliary complications at six months. The peaked median AST level between days 1 and 7 in the five trials was 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 ranged within 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. A single case of PNF was reported in NMP group in the randomized trial while none of the other preliminary studies reported any in either group. There was intertrial variability in EAD which ranged within 15–56% in NMP group while being within 23–37% in SCS group. Biliary complications observed in NMP group ranged from 0 to 20%. Single device malfunction was reported in randomized controlled trial leading to renouncement of transplant while none of the other trials reported any machine failure, although two user related device errors inadvertent were reported. Conclusion This review outlines that NMP not only demonstrated safety and efficacy but also provided the favourable environment of organ preservation, repair, and viability assessment to donor liver prior to the transplantation with low rate of posttransplantation complication as PNF, EAD, and biliary complication; however further studies are needed to broaden our horizon.

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