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

Abstract

Background

Liver retransplantation (reLT) is a well-accepted treatment for liver graft failure in selected patients. A rescue hepatectomy (RH), on the contrary, is a rare and controversial procedure in which a deteriorating liver graft causing failure of other organ systems is removed to stabilize the patient’s condition before a new liver graft is available.

Material/Methods

In this retrospective cohort study, we evaluated the outcomes of the 104 patients who were listed for a first single-organ reLT in our center during the period 2000–2019, to compare the results after RH to other reLTs.

Results

In the study population, RH was performed on 8 patients, while 7 of these received a new graft (8% of all first time reLTs) and 1 died before reLT. All RHs were performed within 1 week after the first transplantation. The median anhepatic time after RH was 36 hours (range 14–99). The 1-year patient survival rate was 57% for reLTs with RH and 69% for acute reLTs without RH that were performed within 14 days after the first transplantation (P=0.66). The 5-year survival rate was 50% in the RH and 47% in the non-RH group (P=1.0).

Conclusions

The use of RH prior to reLT results in a similar outcome to reLTs without RH. Therefore, RH should be considered in patients with a severe clinical instability caused by a deteriorating liver graft. However, further studies are needed to establish guidelines based on objective parameters for when RH should be performed.

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

During the studied period, 2000–2019, 104 patients were listed for their first reLT, and 87 of these patients were retransplanted. The remaining 17 patients died as active patients on the WL or were removed from the list due to liver failure-related complications or uncontrollable infection. Among the patients on the reLT WL, there were 8 cases of RH, and all but 1 of the patients were retransplanted.

All RHs were performed within the first week (range 0–6 days) after the fLT, with half of the RHs performed already at the end of the fLT operation. Three patients had uncontrollable bleeding from retrohepatic vena cava and/or caval anastomosis, with 2 of them also having clear signs of outflow obstruction with a congested liver and capsular ruptures (Table 1). Four patients had combined hepatic artery thrombosis (HAT) and portal vein thrombosis (PVT). In Cases 2 and 6, a thrombosis was suspected based on the liver Doppler ultrasound findings and the patients were directly explored due to uncontrollable bleeding and circulatory instability, with the diagnosis being confirmed intraoperatively. Computed tomography angiography confirmed the ultrasound findings in Case 5, and in Case 8, the thromboses were confirmed at the fLT. The need for RH and consequent reLT was attributed to PNF in only 1 of the cases. The median anhepatic time (AHT) for the retransplanted patients was 2160 min (840–5938 min), and all reLTs after RH were performed within 2 weeks after fLT (median 3 days, range 1–10). The longest AHT was 98 h 58 min. The only RH patient who was not retransplanted died after AHT of 41 h due to bleeding and circulation collapse. Half of the RH patients, including the patient who died before reLT, received MARS treatment during the AHT.

Table 1.

Patients who underwent RH.

Patient	Sex, age	Primary diagnosis	Reason for RH	Uncontrollable bleeding	Severe circulatory instability
1	M 64 y	Ethyl cirrhosis	IVC and caval anastomosis bleeding	Yes	Yes
2	F 8 m	Biliary atresia	HAT + PVT (US and intraoperative findings)	Yes	Yes
3	M 56 y	Ethyl cirrhosis	IVC bleeding and outflow obstruction	Yes	Yes
4	M 52 y	HBV cirrhosis	IVC bleeding and outflow obstruction	Yes	Yes
5	F 7 m	Biliary atresia	HAT + PVT (US and angio-CT)	No	Yes
6	F 9 y	Adams-Olivers syndrome	HAT + PVT (US and intraoperative findings)	Yes	Yes
7	F 67 y	PBC	PNF	No	Yes
8	M 3 y	Biliary atresia	HAT + PVT (intraoperative findings)	No	Yes
Patient	Interval between fLT and RH (h)	AHT (h)	MARS	Outcome
1	3	16	Yes	Alive after 15 years of follow-up
2	40	60	No	Death due to graft failure POD69
3	4	41	Yes	No graft available, death on the reLT WL
4	3	25	Yes	Alive after 8 years of follow-up
5	136	99	No	Alive after 7 years of follow-up
6	24	14	No	Death due to pneumonia POD12
7	12	97	No	Death due to urosepsis POD200
8	5	36	Yes	Alive after 3 years of follow-up

RH – rescue hepatectomy; fLT – first live transplantation; h – hour(s); AHT – anhepatic time; MARS – Molecular Adsorbent Recirculation System; M – male; F – female; y – year(s); m – months(s); IVC – inferior vena cava; HAT – hepatic artery thrombosis; PVT – portal vein thrombosis; US – liver ultrasound; POD – postoperative day; reLT – liver retransplantation; WL – waiting list; PNF – primary non-function; CT – computer tomography.

As all patients who were retransplanted after RH were retransplanted within 2 weeks and thus categorized as acute reLTs, they were compared to the 16 patients who underwent acute reLT without RH (median 7 days, range 1–14). ReLT waiting time, defined as time between listing for reLT and either reLT or removal from the WL due to death or not being transplantable, did not differ between retransplanted patients and patients who died before reLT. The patient characteristics and operation details of acute reLTs with RH compared to acute reLTs without RH are presented in Table 2. The proportion of pediatric patients was significantly higher among the retransplanted RH patients compared to non-RH reLTs, which affected many size-related parameters, such as portal flow and the proportion of split or reduced grafts. There were no differences in preoperative laboratory values, MELD score or non-size-related perioperative measurements, except for higher pre-reLT ALT in patients without RH (median 9.00 vs 1.69, P=0.009). Patients with RH received their second liver graft from donor with a longer ICU stay (median 4 vs 2 days, P=0.031), but there were no other donor-related differences.

Table 2.

Characteristics of patients who were listed for acute reLT with and without RH.

	Listed for acute reLT with RH (n=8)	Listed for acute reLT without RH (n=18)	P-value
Gender (female/male)	4/4	8/10	0.563
Age (years)	31.7 (0.6–67.2)	50.5 (0.5–64.8)	0.892
Paediatric (%)	50	22.2	0.169
Primary diagnosis
Biliary atresia	3	1
HCC	0	2
Cholestatic disease	1	6
Metabolic disease	0	1
Viral hepatitis	1	5
Ethyl cirrhosis	1	0
Acute liver failure	0	3
Other	1	1
MELD fLT	15.5 (8–40)	16.8 (7–40)	0.878
Weight fLT	44.2 (6.6–125.0)	74.3 (7.5–128.5)	0.196
Split or reduced graft fLT (%)	37.5	22.2	0.361
Operation time fLT (min)	560 (382–927)	469 (185–755)	0.062
Total ischemia time fLT (min)	492 (201–970)	596 (379–765)	0.177
Perioperative bleeding fLT (l)	3.3 (0.6–72)	5.3 (0.9–30)	0.925
Reason for reLT
PNF	1	9
HAT	0	5
PVT	0	1
HAT + PVT	4	1
Bleeding	3	0
Other	0	2
Death on WL	1	2	0.686
Time on WL for reLT (days)	2 (0–4)	2 (0–14)	0.605
Split or reduced graft reLT (%)	57.1	12.5	0.045
Operation time reLT (min)	335 (243–660)	290 (165–695)	0.141
Total ischemia time reLT (min)	430 (183–647)	507 (249–659)	0.400
Perioperative bleeding reLT (l)	2.5 (0.6–20)	2.1 (0.4–60)	0.911

MELD and BMI are only presented for adult recipients. reLT – retransplantation; MELD – model for end-stage liver disease; BMI – body mass index; WL – waiting list; HCC – hepatocellular cancer; PNF – primary non-function;HAT – hepatic artery thrombosis; PVT – portal vein thrombosis.

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.

Figure 1.

Patient survival after acute reLT with and without RH. SPSS statistics 25.0, IBM.

Table 3.

Complications after acute reLT.

	Acute with RH (n=7)	Acute without RH (n=15)	P-value
Biliary complication
AS	0	1	0.682
NAS	0	0	0.455
Biliary leakage	0	2
Vascular complication
PVT	0	0	0.682
HAT	0	1	0.318
Outflow obstruction	1	0
Kidney failure	0	1	0.682

reLT – liver retransplantation; RH – rescue hepatectomy; AS – anastomotic stricture; NAS – non-anastomotic stricture; PVT – portal vein thrombosis; HAT – hepatic artery thrombosis.

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.

Abbreviations

AHT

anhepatic time

ALT

alanine aminotransferase

AST

aspartate aminotransferase

BMI

body mass index

fLT

first liver transplantation

ICU

Intensive Care Unit

INR

international normalized ratio

HAT

hepatic artery thrombosis

HCC

hepatocellular cancer

MARS

molecular adsorbent recirculation system

MELD

model for end-stage liver disease

PLT

platelet count

POD

postoperative day

PVT

portal vein thrombosis

reLT

liver retransplantation

WL

waiting list