04 May 2023: Articles
Successful Transplantation of a Liver from a Donor with HELLP Syndrome Undergoing Hypothermic Oxygenated Machine Perfusion (HOPE) Prior to Implantation
Unusual setting of medical careDaniel A. Morales Santana1ABCDEFG*, Iakovos Amygdalos 1BCE, Franziska A. Meister1E, Jan Bednarsch1E, Andreas Lambertz1E, Pavel Strnad 2EF, Alexander Koch 2E, Tom Florian Ulmer1E, Ulf P. Neumann1E, Sven A. Lang1ACDEF
Am J Case Rep 2023; 24:e938131
BACKGROUND: Liver transplantation (LT) has become the treatment of choice for patients with end-stage liver disease (ESLD). The organ shortage forced clinicians to use livers from donors with certain risk factors, so-called extended-criteria donor (ECD) organs. Hypothermic oxygenated machine perfusion (HOPE) is an alternative to conventional static cold storage and reduces early allograft injury in ECD organs. In this article we present the case of a 45-year-old man with hepatitis B virus (HBV)-associated cirrhosis and hepatocellular carcinoma (HCC) who underwent successful liver transplantation supported by pretransplant hypothermic oxygenated machine perfusion (HOPE) from a 34-year-old extended-criteria donor (ECD) with hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome.
CASE REPORT: Liver transplantation was scheduled for a 45-year-old man with hepatocellular carcinoma (HCC) due to hepatitis B virus-induced liver cirrhosis. The organ donor was a 34-year-old woman who had developed intracerebral hemorrhage and brain death due to HELLP syndrome after delivery. Compared to the day of admission to the intensive care unit, a decrease in the donor’s transaminases was observed prior to organ procurement. Before transplantation, HOPE was conducted after regular back-table preparation of the graft. LT was performed according to the standard surgical techniques and a standardized immunosuppressive regimen was conducted. In the post-transplant period, transaminases peaked directly after the operation and normalized after 1 week. No major surgical complications occurred. The patient was discharged after a 24-day hospital stay with normal liver function.
CONCLUSIONS: This case report supports the benefits of using HOPE in ECD organs and it should be considered in livers of donors with HELLP syndrome to improve post-transplant outcome.
Keywords: HELLP Syndrome, HOPE, Liver, Transplants
Since the first successful liver transplantation (LT) in 1967, this procedure has become the treatment of choice for patients with end-stage liver disease (ESLD) . Technical and medical advances have led to an increasing number of indications for LT over the years. Thus, the key problem is now the disparity between the availability of donor organs and the number of patients seeking transplantation . This acute organ shortage has led to the acceptance of expanded-criteria donors (ECD) allografts, which were previously considered inadequate for transplantation.
Although the use of ECD allografts is daily practice, the quality of these organs increases risk of negative postoperative outcomes. To overcome this, machine perfusion (MP) for ECD-allograft transplantation was developed. This procedure decreases organ damage and contributes to organ reconditioning before transplantation. Particularly, hypothermic (oxygenated) machine perfusion (HOPE) demonstrated a reduction of early allograft injury and improve the outcome after LT [3,4].
HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) is a dangerous complication in pregnancy. It is associated with hepatic disfunction, which can cause cerebral hemorrhage, and maternal brain death in the worst case . The use of organs from pregnant women who have died due to complications of HELLP syndrome has rarely been described.
The obvious concern is that the use of a damaged, necrotic liver may have severe consequences for the transplant recipient. However, the quality of the graft can only be assessed by the laboratory values prior to procurement, in addition to the macroscopic and microscopic evaluation during organ retrieval.
Additionally, the organ recipient must be thoroughly and appropriately selected to reduce the risk of post-transplant complication and early allograft disfunction. In this case report, we describe a successful LT of a graft from a donor with HELLP syndrome, who underwent HOPE prior to transplantation.
THE LIVER TRANSPLANT DONOR:
A 34-year-old woman was admitted to the intensive care unit (ICU) directly postpartum, with clinical and laboratory evidences of HELLP syndrome. On admission, blood analysis showed an elevation of aspartate transaminase (AST), alanine transaminase (ALT), and bilirubin to 1335 U/l, 762 U/l and 2,95 mg/dl, respectively, and a decrease in platelets to 30×109/L. The patient’s general condition deteriorated dramatically, and a cranial computed tomography scan revealed a fatal intracerebral hemorrhage. Diagnosis of brain death was made, and the process of organ donation was started according to the local legal requirements. At the time of organ procurement, laboratory values showed an AST, ALT, and bilirubin of 103 U/L, 186 U/L and 0.92 mg/dL, respectively (Figure 1).
On exploration at our institution, the graft showed macroscopically normal shape, color, and consistency, with no anatomical variations. The frozen-section histology showed no necrosis, with a macrovesicular steatosis of 0–5% and a microvesicular steatosis of 61–70%. After standardized back-table preparation of the liver, end-ischemic HOPE Liver Assist (Organ Assist, Groningen, The Netherlands) was applied through the portal vein for about 90 minutes prior to implantation in a pressure-controlled system (2–3 mmHg) with 3 L of oxygenized (target pO2 of 60–80 kPa) and cooled (10°C) re-circulating with Belzer MPS (machine perfusion solution) (Bridge to Life, London, UK) solution . The liver was subsequently flushed after HOPE prior to implantation with 1 L of HTK (histidine-tryptophanketoglutarate) (Custodiol, Dr. Franz Köhler Chemie GmbH, Bensheim, Germany).
THE LIVER TRANSPLANT RECIPIENT:
The recipient was a 45-year-old man with hepatitis-B-associated liver cirrhosis and hepatocellular carcinoma with a lab MELD (model for end-stage liver disease) score of 10 (exception MELD score 25). LT was performed in standard techniques with total vena cava replacement, arterial reconstruction with an anastomosis between the common hepatic artery/splenic artery patch of the donor and the proper hepatic artery/gastroduodenal patch of the recipient, and end-to-end portal vein reconstruction. The graft was reperfused after the portal vein anastomosis. Afterwards, an end-to-end bile duct anastomosis was performed. Cold ischemia time was 9 hours 28 minutes, while warm ischemia time was 45 minutes. Standardized immunosuppression regimen consisted of basiliximab (Simulect 20 mg, NOVARTIS Pharma GmbH), tacrolimus (Prograf, Astellas Pharma GmbH), mycophenolate mofetil (CellCept 500 mg, Roche Pharma AG) and corticosteroids. Cytomegalovirus serology was negative in the donor and positive in the recipient.
Immediate postoperative laboratory values showed an increase of AST (716 U/L), ALT (288 U/L) and bilirubin (2.32 mg/dL). These parameters returned to normal within 1 week (Figure 2). No major complications, defined as ≥3b on the Clavien-Dindo (CD) scale , were observed. The patient had postoperative acute kidney failure KDIGO 3 (CD 2). At discharge, the serum creatinine was 2.55 mg/dL and glomerular filtration rate (GFR) was 29.2 mL/min, with normal urine production. The patient was discharged in good clinical condition 24 days after transplantation. A 3-month follow-up showed excellent graft function.
To the best of our knowledge, this is the first case report describing successful LT of a liver from a donor with HELLP syndrome undergoing HOPE prior to transplantation. Due to medical advances along with technical and pharmaceutical improvements, the number of indications requiring LT has increased considerably in recent decades, but the number of available donor organs does not satisfy current demand. The use of marginal organs that were previously rated ineligible for organ donation, so-called ECD allografts , is one of the strategies addressing this situation. This necessary development is decisively facilitated by pharmaceutical and technical advancements that allow the processing of such potentially critical organs .
HELLP syndrome (hemolysis, high liver enzymes, and low platelets) was first described in 1982. It is a multi-systemic disorder that continues to be a major cause of maternal and neonatal mortality and morbidity, with an incidence of 0.17–0.85% of all pregnancies [5,9]. A number of life-threatening complications for pregnant women are associated with HELLP syndrome, including placental abruption, pre-term delivery, pulmonary edema followed by acute respiratory distress, disseminated intravascular coagulation, cerebral hemorrhage, septic shock, acute renal failure, and hepatic hemorrhage due to hepatic rupture . In case of brain death due to complications of HELLP syndrome, organ donation has rarely been considered.
In the last 2 decades, few cases of liver transplantation from deceased donors with HELLP syndrome have been described in the literature. Due to the characteristics of HELLP syndrome with hemolysis, high liver enzymes, and low platelets, which can lead to severe liver damage, the use of organs from donors with HELLP syndrome is controversial. The published cases of successful LT generally presented with a similar transaminase profile with an improvement from admission at ICU to organ harvesting. Moreover, biopsy after organ procurement showed minimal areas of necrosis [11,12]. However, Karadagi et al  described a case of liver transplantation from a donor with HELLP syndrome in which the recipient developed a clinical picture similar to HELLP syndrome on day 7 post-transplant and underwent emergency liver retransplantation. Briceno et al  recommended that experienced surgeons should guide liver procurements and analyze the microscopic findings from donors with HELLP syndrome to increase the chances of a favorable outcome. In case of severe hepatic necrosis, organs should be discarded. Particularly, Woodside et al  described a case with progressive hepatic necrosis through cold storage and transport that made the liver unsuitable for use.
To prevent the damage caused during static cold storage, MP has become an option for graft preservation by reducing ischemia reperfusion injury as well as preconditioning organs prior to transplantation . In a recent randomized controlled clinical study, Czigany et al demonstrate the benefits of HOPE in LT, reducing serum ALT and attenuating effects on early allograft injury. Furthermore, the use of MP is related with less peri-operative morbidity and shorter ICU and hospital stays, being an established method supported by clinical trials [16–18]. In the current case, we observed a prompt decrease of transaminases down to normal values 1 week after transplantation. No major complications were observed, and the patient was discharged in good condition on the 23rd postoperative day.
In conclusion, LT from donors who die from HELLP syndrome is controversial. Apart from profound ethical, religious, and medico-legal questions about the mother and fetus, the safety of the recipient of the donated organ must be accurately evaluated. Given the encouraging recent data, we suggest the use of HOPE prior to LT instead of static cold storage to avoid graft injury and to improve postoperative outcome. Alternatively, normothermic machine perfusion can be considered in LT from donors with HELLP syndrome, as it maintains the liver in a normal metabolism throughout the preservation period, avoids cooling, and allows recovery (eg, reduction of hepatic steatosis) and functional testing [19,20]. This should be evaluated in further studies.
This case report has certain limitations. At present, no follow-up data regarding the impact of the donor’s HELLP syndrome on long-term organ function are available. Furthermore, limited experience with organs from donors with HELLP syndrome is available and this hampers validation of our results. Finally, identification of the most promising MP approach for liver preservation in this special setting would be desirable but presumably not possible due to the low number of eligible donors with HELLP syndrome.
This report supports the benefits of using pretransplant HOPE in cases of ECD organs in LT. Although the outcome was successful in this case, despite the use of a graft from a donor with HELLP syndrome, caution and rigorous follow-up are required to ensure that long-term complications do not occur in transplant recipients.
FiguresFigure 1.. Trajectories of laboratory values of the donor patient with HELLP syndrome before organ harvesting. The acute elevation of laboratory values after admission in concordance with clinical course. On the day of organ procurement, laboratory values were reduced to approximately one-third of the acute phase values. AST – aspartate aminotransferase; ALT – alanine aminotransferase. Figure 2.. Trajectories of the laboratory values of the recipient after transplantation. The recovery of laboratory values from POD 2 with normalization after 1 week. AST – aspartate aminotransferase, ALT – alanine aminotransferase, POD – postoperative day.
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