Results of Liver Retransplantation After Rescue Hepatectomy: A Single-Center Study

Background

The most common indications for liver retransplantation (reLT) early after first liver transplantation (fLT) are primary non-function (PNF) and thrombovascular complications, whereas recurrence of primary disease, chronic rejection, and biliary complications account for the majority of late reLTs [1–5]. In cases of PNF and other causes for early failure of the liver graft, the deterioration of liver function is rapid, and it may also result in severe dysfunction of other organ systems, leading to hemodynamic instability, multi-organ failure and, eventually, the patient’s death [6]. The deteriorating liver graft not only fails to serve its metabolic function but also produces and leaks toxic substances to the patient’s circulation and is thus called toxic liver syndrome [7]. Occasionally, the need for acute removal of the liver graft is so evident that surgeons may decide to perform a rescue hepatectomy (RH) as a first part of a 2-stage reLT procedure, in which the deteriorating first graft is removed before a new graft is available [8]. In RH, a temporary portocaval shunt is established to achieve sufficient circulatory and clinical stabilization so that the patient can be further managed in an intensive care unit (ICU) while waiting for a new liver graft, and enormous intensive care efforts are required to maintain the patient in a prolonged anhepatic state. Thus, RH is an uncommon procedure performed only in critical situations when other options are few, and there are only a few studies, mainly case reports, describing its role before retransplantation [8–17]. Furthermore, there have been few reports on results after a RH compared to a standard acute reLT, and it is unknown whether RH before reLT affects the long-time outcome. In this study, we analyzed the liver retransplantations performed in our center in the past 2 decades to evaluate the impact of RH on the long-term results.

Material and Methods

STUDY POPULATION:

A retrospective cohort study was performed on patients who were listed for their first reLT at Karolinska University Hospital in Stockholm between January 2000 and December 2019. Patients who had undergone their first transplantation at other hospitals or had received a multi-organ transplantation, either previously or at the same time as reLT, were excluded from the study.

RHs were then identified by assessing the operation journals of patients with an AHT exceeding 3 hours. As there are no commonly defined indications when RH should be performed, decisions to perform RH in our patients were made by the responsible surgeon, with support from other members of the transplant team, on a case-by-case basis. The most important driving factors in the surgeon’s decision to perform RH were the dynamics of respiratory, circulatory, and metabolic deterioration in each patient. The key aspect considered was whether leaving the deteriorating liver graft in the recipient would worsen the patient’s general status within hours to such a degree that the patient would have to be removed from the waiting list (WL) for reLT. In most cases, the decision to perform RH was made before receiving information about the availability of a new liver graft. To identify a control group for the patients who underwent a RH, the patients without RH were divided into 3 groups: acute (within 2 weeks days after fLT), early (between 2 weeks and 3 months), and late (after 3 months), based on the timing of their reLT.

DATA COLLECTION:

Data were collected from the local liver transplantation registry (Ekvator) and supplemented with information from patients’ medical records when needed. Missing data were added using the Scandiatransplant database for organ transplantation (YASWA). The collected data contained characteristics of recipients and donors, as well as perioperative variables from both the recipient and the donors for both the primary transplantation and the retransplantation. Recipient variables included age, sex, weight, body mass index (BMI), primary diagnosis, model for end-stage liver disease (MELD) score prior to fLT and reLT, and date and cause of death. Liver graft function was assessed based on daily standard liver blood tests, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), international normalized ratio (INR), bilirubin, and platelet count (PLT) preoperatively and 3 months, 1 year, and 5 years after retransplantation. The data also included whether a patient had had a biliary or vascular complication or kidney failure requiring permanent renal replacement therapy with dialysis or kidney transplantation during the follow-up. Donor variables included age, sex, weight, BMI, length of ICU stay prior to donation, cause of death, and last available ALT, AST, and bilirubin before donation. The perioperative variables included type of graft (whole liver or living/reduced/split liver), operating time, cold and warm ischemia time, intraoperative bleeding, perioperative blood transfusions, and anhepatic time (AHT). For patients undergoing RH, we collected data on the postoperative day when RH was performed, and if the molecular adsorbent recirculation system (MARS) was used prior to or during AHT.

STATISTICAL ANALYSIS:

Data are mainly presented as a median (range). The t test was used for continuous variables with normal distribution. Non-normally distributed and nonparametric variables were tested using Mann-Whitney U test. Pearson’s chi-square test and Fischer’s exact test were used to analyze the significance of an association between 2 categorical variables. The Kaplan-Meier test was used for survival analysis. Test results with P values <0.05 were considered statistically significant. Statistical analysis was performed using SPSS statistics 25.0 (IBM, Armonk, NY, USA).

Results

OUTCOME AFTER RETRANSPLANTATION:

All patients with RH survived the reLT operation, while there was 1 intraoperative death (6.3%) in the acute reLT group without RH. The total perioperative mortality for acute reLTs was 17.4%, with 1 death (14.3%) in the RH group and 3 in the non-RH group (18.8%). In the RH group, 1- and 5-year patient survival was 57.1% and 50%, respectively (Figure 1). In the group of acute reLTs without RH, the 1-year patient survival was 68.8% and the 5-year survival 46.7% (P=0.657 and P=1.0, respectively). The most common causes of death were infections (50%) followed by bleeding complications (25%). There were no differences in laboratory test values or incidence of complications (Table 3) between the groups. None of the acutely retransplanted patients underwent a third liver transplantation during the follow-up, graft survival thus equaling patient survival in both the RH and non-RH group.

Discussion

This retrospective study was conducted to gain more insight into RH and outcome after 1 in the context of reLT. To the best of our knowledge, this is the first cohort study comparing long-term results after RH vs results of other reLTs.

RH has been suggested as a bridging procedure before a liver transplantation when a patient’s life is threatened by toxicity caused by the failing liver or exsanguination from the liver [8]. As there are no established policies with standardized indications and objective parameters for when RH should be performed, the decision to perform a RH is still made by individual surgeons in each case, which leads to very subjective decision-making relying on the surgeon’s experience and difficulties comparing different cases with each other. The exact decision-making process in each case was also difficult to analyze due to the retrospective nature of our study. However, in many cases, factors such as high lactate values and need for several vasopressors with a maximal dosage played an important role in it. Nevertheless, we would like to stress that the decision of performing RH, at least in our study population, is made in emergency situations where other measures have been deemed insufficient and the prognosis extremely poor. The question of whether hepatectomized patients would have a different outcome without a RH is difficult to answer. In our study, the only RH patient who died before reLT had a relatively long AHT of 41 h compared to many other reports [9,10,12–15]. However, there have been several patients surviving a longer anhepatic time with a good outcome, both in our study and in the literature [9,11,16,17]. It is also difficult to determine a time limit between AHT and reLT beyond which reLT may be considered futile, both due to lack of data on the subject and variability in the deterioration of a patient’s condition from case to case [18]. As RHs were performed within the first 14 days after the fLT, all RH patients qualified for an “urgent call” within Scandiatransplant [19]. The average waiting time on the urgent call WL is relatively short, supported by the fact that only 1 patient (12.5%) died before a new graft was available. That is comparable to mortality for non-RH patients on the same WL in our study and, for example, to the mortality on the Eurotransplant’s urgent and United Network for Organ Sharing status 1a WL [20,21]. Thus, from the organ availability point of view, RH should be considered a feasible alternative, as the organ supply in critical situations is relatively good, at least in these areas. Furthermore, the number of deaths on the WL has not increased over the studied period, although the number of reLTs has been rising, which also seems to be a trend in the Nordic countries [22].

The small number of patients made it difficult to perform any further subgroup analyses, including analyzing pediatric patients as a separate group. The small sample size – 87 retransplanted patients and only 8 patients with RH during the 20-year study period – is undeniably the main limitation of this study. All conclusions should therefore be tentative. Nevertheless, RH did not seem to affect the outcome in our patients. The long-term survival after reLTs with a prior RH is the same as the results of other acute reLTs, and can therefore be regarded as good, which indirectly validates RH as an emergency alternative in unstable patients with questionable graft viability and function and who do not respond to other treatments.

Conclusions

The use of RH prior to reLT results in the same patient survival rate as acute reLTs without RH. RH should therefore be considered in patients with deterioration of the first liver graft and with clinical instability. However, further studies are needed to establish guidelines based on objective parameters for when RH should be performed.