Objectives: Liver retransplant is the only therapeutic option for irreversible liver graft failure. Its incidence varies between 5% and 22% worldwide. Liver retransplant - despite some recent improvement - is associated with significantly poorer outcome compared with the primary transplant.

The purpose of this study was to assess the outcome of liver retransplant compared with primary liver transplant, compare the outcome of early and late liver retransplant, and to evaluate the outcome of liver retransplant within different predictive index categories.

Materials and Methods: We retrospectively reviewed adult patients who had liver retransplant from May 2001 to December 2013. Patients were divided into 2 groups: group A (early liver retransplant), retransplant within 30 days; and group B (late liver retransplant), retransplant > 30 days after primary liver transplant.

Results: After 460 primary adult liver transplants, 17 liver retransplants (3.7%) were performed in 16 adults. Mean patient survival after liver retransplant was 29.5 ± 31.9 months. The 1-, 3-, and 5-year patient survival was 68.8%, 51.6%, and 38.7%. Mean graft survival following liver retransplant was 27.9 ± 32.1 months, and 1-, 3-, and 5-year graft survival was 51.5%, 34.3%, and 22.9%. Patient and graft survival was significantly better in group B than group A at 1 year and 3 years. There were 9 liver retransplants (52.9%) with predictive index category IV; 7 retransplants (41.2%) with predictive index category III; and 1 retransplant (5.9%) with predictive index category II. Patient survival was significantly higher for predictive index category III than IV at 1 year and 3 years.

Conclusions: Patient and graft survival are lower after liver retransplant than primary liver transplant. Graft and patient survival are better in late than early liver retransplant and in predictive index category III than IV.

Key words : Complications, End-stage liver disease, Liver transplant, Survival

Introduction

Liver transplant is an established treatment for its approved indications. Currently, 1- and 5-year survival rates after liver transplant are 90% and 70%. However, many patients (10%-19.4%) have graft loss after primary liver transplant.^1,2 Liver retransplant is the only therapeutic option for irreversible liver graft failure. The incidence of retransplant varies between 5% and 22% worldwide.^3-6

The situation of liver retransplant is complex. It involves financial and ethical issues. It is associated with higher costs and it results in a missed opportunity for primary transplant in another patient. This has importance due to the increasing donor organ shortage.^7,8 Moreover, despite some recent improvements, liver retransplant is associated with significantly poorer outcome than primary transplant; based on data from United Network for Organ Sharing, graft survival at 1, 3, and 5 years after liver retransplant was 82.6%, 74.2%, and 56.0% and after primary liver transplant was 92.4%, 86.1%, and 69.9%.1 This difference in outcome has been confirmed in numerous reports.^9-14

It is important to distinguish between liver retransplant performed for early or late indications. Early after primary liver transplant (within the first 30 d), the indications usually are urgent, and this carries special concern regarding evaluation to exclude cases with refractory sepsis, brain herniation, or multiorgan failure. However, early liver retransplant is technically easier, especially within 1 week, than late liver retransplant.³ Late after transplant, the situation is much more complicated because patients usually have comorbidities that contribute to medical complexity such as renal failure, recurrent infection, and use of immuno­suppression. Furthermore, liver retransplant is technically demanding due to distorted anatomy and vascular adhesions.³

It has been noted that outcome of liver retransplant is variable. Factors were identified that were associated with poor outcome; the value of some of these factors was ascertained, and some risk models were created.^15,16 The purpose of this study was to review data from > 12 years about the outcome of liver retransplant in adults at our center.

Materials and Methods

We retrospectively reviewed our database for cases of liver retransplant for adults from May 2001 to December 2013. Data were collected including demographic data; primary transplant data including type of graft, urgency of transplant, Model for End-Stage Liver Disease (MELD) score before transplant, and donor risk index (DRI) for cases transplanted from a deceased donor; data related to retransplant including interval to retransplant, indication for retransplant, type of graft, urgency of retransplant, MELD score before retransplant, intensive care unit stay, mechanical ventilation, DRI for cases transplanted from a deceased donor, and operative details; and data related to outcome of retransplant including patient survival and graft survival. Liver retransplant procedures were divided into 2 groups: group A (early liver retransplant) included cases transplanted within 30 days after primary liver transplant, and group B (late liver retransplant) included patients who were transplanted > 30 days after primary liver transplant.

Results

Overall and demographic data
From May 2001 until the end of December 2013, there were 460 liver transplants for adult patients performed at our center. Our database revealed 17 liver retransplants for 16 adult patients (retransplant rate, 3.7%) including 10 males (62.5%) and 6 females (37.5%); 15 patients had 1 liver retransplant and 1 patient had 2 liver retransplants.

Primary transplant data
Primary liver transplants were right lobe living-donor liver transplant (LDLT) in 9 patients (56.25%) and whole organ deceased-donor liver transplant (DDLT) in the other 7 patients (43.75%). In their first liver transplant, most patients had elective admissions; 1 patient was admitted to the intensive care unit (6.25%), 2 patients were inpatients (12.5%), and 13 patients were admitted electively to the hospital to undergo primary liver transplant (80.25%). The MELD score for patients before primary liver transplant ranged from 7 to 34 points (mean, 21.2 ± 8.2 points). Indication for liver transplant was end-stage liver disease secondary to hepatitis C virus (HCV) cirrhosis in 7 patients (43.75%), hepatitis B virus (HBV) cirrhosis in 5 patients (31.25%), autoimmune hepatitis in 2 patients (12.5%) and Budd-Chiari syndrome or cryptogenic liver cirrhosis in 1 patient each (6.25%). In addition to these indications, 3 patients had concomitant hepatocellular carcinoma (18.75%). There were 15 patients who had their primary transplant at our institution; the 2 other patients had their primary liver transplant in the United States, and in these 2 patients, deceased-donor data could not be retrieved, and DRI was not calculated. In the other 5 DDLT cases, DRI was < 2 with low risk from the deceased-donor perspective (DRI range, 1.2-1.9 points; mean, 1.46 ± 0.32 points). Therefore, good liver graft quality at the primary liver transplant was present in all retransplanted cases.

Overall data on liver retransplant
There were 15 patients who had 1 liver retransplant and 1 patient who had 2 liver retransplants. There were several different indications for liver retransplant in adult patients (Figure 1).

The overall mean MELD score for patients before the retransplant was 27.5 ± 8.1 points (range, 11-38.3 points). Retransplant was done using whole organ DDLT in all procedures except in 1 procedure that was performed with a right lobe LDLT (the patient’s daughter was aged < 18 years at primary liver transplant later on; she donated the right lobe of her liver to retransplant her father when she was above 18 years.).

Patient survival after liver retransplant was mean 29.5 ± 31.9 months (range, 9-3063 d). Graft survival following liver retransplant was mean 27.9 ± 32.1 months (range, 0-3063 days). The 1-, 3- and 5-year patient and graft survival rates were determined using Kaplan-Meier method (Figure 2).

Comparative data on early versus late liver retransplant
There were 9 procedures (56.25%) in group A (early liver retransplant) and 8 procedures (43.75%) in group B (late liver retransplant). Indications for liver retransplant differed between the 2 groups (Table 1).

In the 9 patients in group A, 1 patient had 2 liver retransplants. Indications for retransplant in this group included graft loss secondary to early vascular complications in 4 patients (44.4%); small-for-size syndrome (SFSS) in 4 patients; and primary nonfunction (PNF) (11.1%) in 1 patient. In group B; all patients had 1 liver retransplant, and the different indications for retransplant were tabulated (Table 1).

The MELD score in group A ranged from 16 to 36 points (mean, 29.3 ± 6.3 points) and in group B from 11 to 38.3 points (mean, 25.4 ± 9.8 points) (Table 2). In group A, all patients were retransplanted using whole-organ DDLT; in group B, patients were retransplanted using whole-organ DDLT except for 1 patient who was retransplanted using right lobe LDLT. Operative time, operative blood loss, and intraoperative transfusion requirements were significantly less in group A than group B (Table 2).

Patient survival in group A (early liver retransplant) ranged from 9 to 3063 days (median survival, 29.8 ± 38.6 mo) and in group B (late liver retransplant) ranged from 51 to 1945 days (median survival, 29.3 ± 26.5 mo). The 1-, 3-, and 5-year patient survival was determined using Kaplan-Meier method for both groups (Figure 3). Using log-rank test, patient survival was significantly different between both groups (log-rank value = 1.89).

Graft survival in group A (early liver retransplant) ranged from 9 to 3063 days (median survival, 26.5 ± 36 mo) and in group B (late liver retransplant) ranged from 51 to 1945 days (median survival, 29.3 ± 26.5 mo). The 1-, 3-, and 5-year graft survival was determined using Kaplan-Meier method for both groups (Figure 4). Using log-rank test, graft survival was significantly different between both groups (log-rank value = 7.85).

Liver retransplant
Liver retransplants were retrospectively assessed according to predictive index categories (PIC) proposed by University of California at Los Angeles (UCLA) workers. The categories were PIC IV in 9 liver retransplants (52.9%), PIC III in 7 retransplants (41.2%), and PIC II in 1 retransplant (5.9%). There were no liver retransplants in the PIC I category. Patient survival following liver retransplant differed according to the PIC category, with PIC III (log-rank value = 15.88) associated with significantly better patient and graft survival than PIC IV (log-rank value = 22.54). Kaplan-Meier method was used to compare patient and graft survival between PIC III and PIC IV categories (Figure 5 and 6).

Discussion

The incidence of liver retransplant varies between 5% and 22% worldwide. Our liver retransplant rate was lower than this range (3.7%). This can be attributed to the severe shortage of deceased-donor grafts in Saudi Arabia, especially at the beginning of the liver transplant program in Saudi Arabia. This is compounded by the absence of a national allocation policy, and might have been affected by the learning stage, which may have limited the performance of retransplants.

The SFSS was the most common cause of retransplant in our series (23.5%), followed by early hepatic artery thrombosis (HAT) (17.6%), recurrence of original disease (17.6%), chronic rejection (11.8%), late vascular complications (11.8%), and, rarely, PNF (5.9%) and biliary complications (5.9%). Bramhall and coworkers2 reported HAT as the most common indication for retransplant (31.6%), followed by chronic rejection (22.4%), recurrent disease (13.2%), and PNF (10.7%). The HAT was not the most common reason for our retransplants. This can be attributed to routine use of operative microscopy for hepatic artery anastomosis at our center and failure to retransplant cases of HAT in a timely fashion because of the lack of a national allocation policy at the start of the liver transplant program in Saudi Arabia. The reason that SFSS was the commonest indication for retransplant at our center was the lack of reconstruction of anterior segment veins in right lobe LDLT, especially at the start of our liver transplant program, which led to the frequent occurrence of anterior segment congestion and SFSS.

Operative time, operative blood loss, and intraoperative transfusion requirements were significantly lower in early than late retransplants. These findings are consistent with many previous reports and may be attributed to distortion of anatomy and presence of dense, vascular adhesions and portal hypertension.

Our data showed better 1- and 3-year patient and graft survival in late than early retransplants. At 5 years, the early group had slightly better patient and graft survival than the late group. This can be explained partially by worsening of survival in the late group due to development of graft cirrhosis secondary to recurrence of HCV.

Recently, workers at UCLA developed the PIC scoring system in which patients were stratified into 4 classes that were highly predictive of patient and graft survival. The authors recommended reserving liver retransplant for patients with PIC I to III but not patients with PIC IV.16 The present data confirm better survival of patients with PIC III than PIC IV, similar to data from the UCLA researchers. Evaluation of the details showed that patient survival after liver retransplant in our cohort paralleled the UCLA data (50% and 25% at 5 years for PIC III and PIC IV in our data compared with 49% and 22% in the UCLA data). However, our 5-year graft survival after liver retransplant was slightly worse than reported by the UCLA workers for PIC III (UCLA, 43%; present study, 26.7%) and slightly better for PIC IV (UCLA, 19%; present study, 22.2%). This can be attributed to the smaller sample size in the present study.

In summary, liver retransplant is the only therapeutic option for irreversible liver graft failure. However, organ shortage and logistic reasons may prevent patients from timely retransplant. Our patient and graft survival were lower after liver retransplant than primary liver transplant, especially when early liver retransplant was considered. This mandates the application of the risk stratification model to predict optimal retransplant procedures. The PIC categories were relevant retrospectively for predicting outcome after liver retransplant.

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