Transplantation of Severely Steatotic Liver Grafts After Machine Perfusion Remains a Risky Challenge

Abstract

Liver transplantation is the treatment of choice for patients with end-stage liver disease. However, donor shortages have increased the use of high-risk and extended criteria donor livers, including livers donated after circulatory death and those with severe steatosis. Severe donor liver steatosis is associated with poor outcomes due to high susceptibility to ischemia-reperfusion injury. Ex situ machine perfusion, combining hypothermic oxygenated perfusion and normothermic perfusion (termed the DHOPE-COR-NMP protocol), has emerged as a promising strategy to mitigate injury, assess liver viability, and improve transplant outcomes. Here, we present two patients who received very steatotic donor livers following resuscitation and viability assessment using DHOPE-COR-NMP. Although both steatotic donor liver functioned well during NMP and met all of our clinically validated viability criteria, the outcome after transplantation was complicated. One recipient suffered from pulmonary fat emboli syndrome, likely due to significant loss of fat from the donor liver. The second patient required retransplantation and histopathological examination of the donor liver revealed massive lipopeliosis in zones III of the explanted liver. With the increasing incidence of steatotic donor livers, further research to prevent steatosis-related posttransplant complications is becoming progressively important. At present, transplantation of severely steatotic liver grafts remains a risky challenge, even after ex situ machine perfusion.

Keywords: complication; donors and donation: extended criteria; liver biology.

FIGURE 1

Summary of donor and recipient of Case 1. (A) Macroscopic image of the 3025 g donor liver on the backtable prior to machine perfusion. (B) Hematoxylin and eosin histology of liver parenchyma prior to machine perfusion showing severe steatosis (approximately 60%). Scale bars 250 µm, magnification 10×. (C) Graph showing evolution of recipient serum creatinine, lactate, and prothrombin time. (D) Graph showing recipient serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin after transplantation. On postoperative day 17, the patient underwent re‐transplantation. (E) Hematoxylin and eosin histology of the explanted liver showing severe macrovesicular steatosis (60%–70%) with moderate sinusoidal and perivenular fibrosis. Scale bars 100 µm, magnification 10×. (F) Hematoxylin and eosin histology of explanted liver showing lipopeliosis. Scale bar 5 µm, magnification 15×.

FIGURE 2

Summary of donor and recipient characteristics of Case 2. (A) Macroscopic image of the 2944 g donor liver on the backtable prior to machine perfusion (B) Hematoxylin and eosin histology of liver prior to machine perfusion. Histological steatosis was present but appeared less severe than expected from macroscopic assessment. Scale bars 250 µm, magnification 10×. (C) Graph showing evolution of recipient creatinine, lactate, and prothrombin time. (D) Graph showing recipient serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and bilirubin after transplantation. (E) Chest X‐Ray on postoperative day (POD) 3 showing consistent interstitial impairment with pleural effusion electively on the right side. (F) Chest x‐ray on POD 8 showing improved lungs with reduced interstitial imbibition and concurrent replacement of the right pleural effusion with a mild blurred obliteration of costophrenic sinus.