Retransplantation for hepatitis C: Results of a U.S. multicenter retransplant study

Authors


  • See Editorial on Page 1217

  • Presented at the International Liver Transplantation Congress, Los Angeles, CA 2005.

Abstract

It is widely perceived that outcomes are relatively poor following retransplantation (reTX) for recurrent of hepatitis C virus (HCV) infection. Transplant centers debate the utility of offering another liver to these patients. A U.S. study group was formed to retrospectively compare survival after reTX in patients with recurrent HCV (histologically proven) and those transplanted for other indications greater than 90 days after first transplantation, from 1996 to 2004. Patients were divided into 3 groups; group 1: HCV reTX (n = 43), group 2: non-HCV reTX (n = 73), and group 3: recurrent HCV but no reTX (n = 156). They were predominantly male, Caucasian, with mean age of 47.2 yr. The commonest indications for non-HCV reTX were chronic rejection (36%), hepatic artery thrombosis (31%) and recurrent primary sclerosing cholangitis (17%). Duration of hospitalization, number of intensive care unit (ICU) days, and time interval from listing to transplantation or reTX were similar between reTX groups. The 1-yr and 3-yr survival rates after reTX were also similar for HCV reTX and non-HCV reTX groups (1 yr, 69% vs. 73%; 3 yr, 49% vs. 55%). Model for End-Stage Liver Disease (MELD) scores were not predictive of survival from reTX. However, with a MELD score of >30 in the non HCV group, survival was <50%. In the recurrent HCV not undergoing reTX group, 30% were reevaluated for reTX but only 15% were listed for reTX and the 3-yr survival was 47%. The most common reasons for not listing for reTX were recurrent HCV within 6 months (22%), fibrosing cholestatic hepatitis (19%), and renal dysfunction (9%). In conclusion, patients retransplanted for recurrent HCV had similar 1-yr and 3-yr survival when compared to patients undergoing reTX for other indications. MELD scores were not predictive of post-reTX survival. Survival was <50% in the non-HCV reTx group with MELD score of >30. Many patients with recurrent HCV are not considered for reTX and die from recurrent disease. Liver Transpl 13:1246–1253, 2007. © 2007 AASLD.

Hepatitis C virus (HCV)-related liver disease is the leading indication for liver transplantation in North America. Virological recurrence of HCV infection is universal, with 20 to 40% of grafts developing cirrhosis by the fifth postoperative year.1, 2 Allograft failure secondary to recurrence of HCV infection is the most common cause of graft failure and death among recipients with HCV infection.1, 2 Efficacy of treatment of the recurrent HCV is limited by many factors, including drug toxicity and immunosuppression, with sustained virological response rates in the range of 30%.3, 4 The progression to graft failure is significant and liver transplant centers are debating the issue of retransplantation (reTX).

Historically, reTX in the United States has accounted for about 10% of all liver transplantations.5 However, over the last 8 years the rate has decreased to approximately 4%.5 One explanation for this finding is that reTX for patients with HCV is believed to be associated with poor outcomes, with many centers reluctant to perform these procedures.6–18 Utilizing the United Network for Organ Sharing registry, Rosen and Martin6 showed worse outcome in patients retransplanted for HCV from 1990 to 1996. In contrast, Watt et al.9 reported similar patient survival in HCV compared to other etiologies, but showed progressively decreased survival as the Model for End-Stage Liver Disease (MELD) score increased, especially when it was greater than 25. While analysis of the United Network for Organ Sharing or Scientific Registry of Transplant Recipients database is helpful, detailed information (e.g., histopathology) concerning the cause of graft failure is lacking. An unknown proportion of patients with HCV infection undergoing reTX in these analyses will have had causes of graft failure other than HCV. There is no data describing the prevalence and outcome of patients with recurrent HCV with graft dysfunction due to HCV recurrence that are not offered reTX.

We formed a U.S. multicenter reTX study group to address some of these issues after this topic was discussed at the International Liver Transplant Society (Phoenix, AZ) Hepatitis C Consensus Conference. The primary aim of this study was to compare outcomes after reTX in patients with graft failure due to recurrent HCV with those of patients undergoing reTX for indications other than recurrence of HCV. The secondary aims were to determine the frequency and fate of patients with graft failure due to recurrent HCV. Finally, we assessed the length of hospitalization after reTX of the different groups.

Abbreviations

reTX, retransplant(ation); MELD, Model for End-Stage Liver Disease; HCV, hepatitis C virus; ICU, intensive care unit.

PATIENTS AND METHODS

We performed a retrospective cohort study using self-reported data from 11 U.S. centers including the University of Alabama, University of California at San Francisco, University of Cincinnati, University of Colorado, Duke University, Mayo Clinic Rochester, Mayo Clinic Scottsdale, University of Nebraska, Oregon Health and Science University, University of Pennsylvania, and the University of Southern California. All patients older than 18 yr of age who were retransplanted more than 90 days after their first transplant from 1996 to 2004 were included in the study. Patients who underwent reTX within 90 days of their primary transplant were excluded from this analysis to exclude patients with primary nonfunction, early hepatic artery thrombosis, or technical complications. Pathologic reports of the explanted organ at reTX and prior histological reports were reviewed to confirm cause of graft failure and reason for reTX. Patients were analyzed in 3 groups: group 1 patients were retransplanted due to recurrent HCV; group 2 patients were retransplanted due to non-HCV causes; and group 3 patients had recurrent HCV but were not retransplanted. Group 3 patients were selected by histological recurrent disease with graft dysfunction. Since this study was retrospective, individual centers decided when to consider revaluation and relisting according to their center-specific criteria for consideration for relisting/reTX. No uniform criterion for revaluation/relisting was used in this study. To evaluate if there was patient selection bias or center differences, risk scores using Rosen et al.'s19 formula of Risk = 10 * [0.0236 * (age at second listing) + 0.125 * √(bilirubin) + 0.438 (creatinine) − 0.234 * (interval to reOLT)] were calculated for groups 1 and 2 to separate patients into low (<16), intermediate (16.1–20.49), and high (>20.5) risk groups. Markmann et al.'s20 survival model was also used to evaluate patients selected for reTX. The study was approved by all centers' institutional review boards and conformed to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the appropriate institutional review committee. Individual patients were referred to by number and not by other identify data.

All analyses were performed using SAS statistical software, version 9.1 (SAS Institute, Cary, NC). Differences in categorical variables between the groups were compared by the Fisher's Exact test. Continuous data were reported as median ± standard error. Differences in continuous variables were analyzed by the Kruskal-Wallis test. Survival estimates were calculated using the Kaplan-Meier method, and confidence intervals for specific estimates of time-to-event distributions were calculated using Greenwood's formula for the variance of the estimates. Comparisons of outcome among the groups were made using the log-rank test. A P value of less than 0.05 was considered statistically significant.

RESULTS

Demographics/Patient Selection

The study population included 272 patients and were grouped as follows: group 1 included 43 patients retransplanted for recurrent HCV; group 2 included 73 retransplanted for non-HCV etiologies; and group 3 included 156 patients who were not retransplanted but had recurrent HCV and graft dysfunction. Four patients were excluded from analysis due to review of histology and inability to conclusively determine the cause of graft failure. Six patients out of 73 patients in group 2 were initially transplanted for hepatitis C. The reasons for reTX in these 6 patients were chronic rejection in 3, hepatic artery thrombosis in 2, and venoocclusive disease in 1 patient. No patients undergoing reTX utilized a living donor. No patient retransplanted had a combined liver and kidney transplant.

The transplant centers enrolled 6 to 51 patients per site, with 5 centers enrolling more than 20 patients (Table 1). Transplant centers enrolled 0 to 9 patients in group 1, 0 to 22 patients in group 2, and 1 to 36 patients in group 3. Patient demographics were similar between all groups, except patients in group 3, which were predominately males (71%) in contrast to groups 1 and 2, which had equal gender distribution. (Table 2) Assessment of previously described variables of poor outcomes at reTX noted: 7% of group 1 and 25% of group 2 patients were >55 yr of age; 58% of group 1 and 54% of group 2 patients had a bilirubin of >5 mg/dL; and 27% of group 1 and 20% of group 2 patients had serum creatinine >2 mg/dL. Type of immunosuppression, genotype, and quantitative HCV viral levels at reTX could not be evaluated due to missing data for these variables in many patients. A total of 19 (44%) of group 1 patients received HCV treatment after their initial transplant. Of those 19, 16 patients received standard interferon, 2 patients were treated with PEG interferon 2a; and 6 patients received PEG interferon 2b and ribavirin.

Table 1. Distribution of Patients by Study Site
SiteGroup 1Group 2Group 3
192220
2369
34136
42314
591810
6321
75416
81512
9007
10152
116729
Table 2. Demographics
 HCV reTXNon HCV reTXHCV no reTX
 N = 43N = 73N = 156
  1. Abbreviations: OLT, orthotopic liver transplantation.

Age (mean yr)47.346.452.2
Gender   
 Male (%)27 (62)38 (52)111 (71)
 Female (%)16 (38)35 (48)45 (29)
Ethnicity   
 Caucasian (%)40 (93)55 (75)113 (72)
 Black (%)2 (5)6 (8)14 (9)
 Hispanic (%)1 (2)6 (8)8 (5)
 Asian (%)0 (0)4 (5)10 (6)
 Other (%)0 (0)2 (3)11 (7)
Donor age*   
 First OLT   
  < 30 (%)9 (26)21 (33) 
  31–50, (%)13 (37)18 (29) 
  >51, (%)13 (37)24 (38) 
 Second OLT   
  <30, (%)14 (38)28 (43) 
  31–50, (%)13 (35)15 (23) 
  >51, (%)10 (27)22 (34) 

Using the Rosen et al.19 survival model, 66% of patients (n = 28) in group 1 were low risk, 24% (n = 10) were intermediate risk, and 10% (n = 4) were high risk patients. Group 2 patients had similar risk distribution, low 67% (n = 49), intermediate 24% (n = 18), and high 9% (n = 6). Variables to calculate risk scores were available in 36 of 46 patients reevaluated for reTX in group 3. These patients in group 3 had risk scores of 47% low risk, 36% intermediate, and 16% high risk. Using Markmann et al.'s20 model of risk assessment, 81% of patients of group 1 were low risk (score of 0–2) and 19% were high risk (score of 3–5). In group 2 patients, 76% were low risk and 24% were high risk. The distribution of group 3's patients was similar, with 78% low risk and 22% high risk. Comparing risk scores between the centers, there was no difference in center-specific distribution of patients retransplanted. Therefore, patients that were retransplanted seemed to be similarly selected by all centers of the study.

Donor age was divided into categories of <30, 31–50, and >50 yr. No differences in donor age among groups 1 and 2 were noted between primary transplantation and reTX (Table 2). Steatotic donor organs (>30% histological steatosis) were used in 2 retransplant patients, both in group 2 and one HCV-positive donor organ was used in group 1.

Yearly reTX rates (2–6 patients/group/yr) were constant for groups 1 and 2 from 1996 through 2004. In contrast, the prevalence of recurrent HCV patients not retransplanted increased dramatically in years 2003 and 2004 in comparison to years 1996 to 2002 (from 10–15 patients/yr to 25–30 patients/yr).

Indications for reTX in group 2 (non-HCV) are summarized in Table 3. Chronic rejection was the most common reason for reTX (36%), followed by late hepatic artery thrombosis (31%) and recurrent primary sclerosing cholangitis (17%).

Table 3. Indications for Retransplantation in Non-HCV Patients
 No. of patients (%)
  1. Abbreviations: HAT, hepatic artery thrombosis; PSC, primary sclerosing cholangitis; PBC, primary biliary cirrhosis; VOD, venoocclusive disease; NASH, nonalcoholic steatohepatitis.

Chronic rejection26 (36)
HAT22 (31)
Recurrent PSC12 (17)
Second Biliary cirrhosis2 (3)
Recurrent Budd Chiari2 (3)
Recurrent PBC2 (3)
Drug2 (3)
Other3 (4)
VOD1 (1)
Recurrent NASH1 (1)

Time Intervals Between Listing and Transplantation

The median waiting list time (days) for first transplant compared to waiting list time for retransplant was markedly different when comparing group 1 and 2 (group 1, 236.5 vs. 81 median days; group 2, 172 vs. 51, median days). However, there was no statistical difference among the 2 groups. The median time (days) from the first transplantation to the second transplantation was not statistically significant between the 2 groups (group 1, 747; group 2, 871).

MELD Score Comparisons Among Groups

The distribution of MELD scores of each group at initial listing, first transplantation, relisting, and reTX are illustrated in Figure 1. Group 3 patients included the MELD score at reevaluation for potential reTX. As expected, MELD score increased at each interval of evaluation from initial transplantation to reTX. At the time of the first listing and transplantation the MELD scores were higher in group 2 and 3 compared to group 1 (first listing, mean MELD score, 13 [6–23] vs. 18 [6–43] vs. 15 [6–43]; first transplant, mean MELD score, 15 [6–28] vs. 20 [6–40] vs. 18 [2–50]). MELD scores at second listing and reTX were distinctly higher than initial listing and transplantation (second listing, mean MELD score, 21 [6–42] vs. 21 [8–43] vs. 25 [10–40]; reTX, mean MELD score, 26 [7–44] vs. 25 [9–46]). In contrast to the primary transplantation, the MELD scores at second listing and reTX were similar in groups 1 and 2, and the majority of patients retransplanted had moderately high MELD scores (mean score >25). It is important to note that the mean MELD score of group 3 patients at the time of reTX evaluation was higher than patients in groups 1 and 2. Patients who were deemed not to be candidates for reTX were sicker and may have been considered to be poor candidates for reTX on this basis rather than based on etiology of graft failure. MELD scores were analyzed prior to 2002 and after 2002 (when MELD was instituted); no differences between the eras or groups were noted (group 1, mean 20.5 vs. 21.4, group 2 mean 21.9 vs. 20.0).

Figure 1.

MELD scores. List 1 = time of initial listing for liver transplantation, Trans 1 = time of initial transplantation, List 2 = time of second relisting, Trans 2 = time of retransplantation.

Survival

The Kaplan-Meier survival curve is shown in Figure 2. Overall 1-yr and 3-yr survival rates after reTX were 69% and 49% for group 1 and 73% and 55% for group 2 (P = 0.74), respectively. Table 4 illustrates the survival of groups 1 and 2 with MELD scores divided by score ranges of <20, 20–25, 25–30, and >30. One-yr and 3-yr survival decreased with higher MELD scores in both groups. When analyzed by MELD scores <25 and >25 there was a significant difference in survival in group 2 (3 yr survival: <25, 76% vs. >25, 54%; P = 0.01), but not in group 1. Survival was significantly different in group 1 patients when they were separated into calculated low risk group (<16) vs. intermediate risk (16.1–20.49) (1-yr and 3-yr survival: low risk 74%, 53% vs. intermediate risk 42%, 21%; P = 0.03). All of the 4 high-risk patients in group 1 survived up to 3 yr. In group 2, survival was similar in all risk groups (1-yr and 3-yr survival: low risk 76%, 70%; intermediate 72%, 43%; and high risk 50%, 50%; P = 0.23) There was no statistically significant difference when comparing group 1 vs. group 2 patients comparing patients in the low risk (R < 16) or intermediate risk group (R = 16.1–20.49). In group 1 patients, survival after reTX was markedly different for patients retransplanted for histological confirmed fibrosing cholestatic hepatitis (n = 4, 1-yr survival 0%) vs. patients with recurrent hepatitis C and cirrhosis (n = 39, 1-yr survival 67%).

Figure 2.

Overall survival. HCV reTX = patients retransplanted for hepatitis C. Non-HCV reTX = patients without hepatitis C retransplanted.

Table 4. MELD Score Survival Outcome
MELD score1-yr survival rate (%) (95% CI)3-yr survival rate (%) (95% CI)5-yr survival rate (%) (95% CI)P value
Group 1   0.97
 <2076 (43–92)56 (23–79)56 (23–79) 
 20–2583 (27–97)42 (1–84)42 (1–84) 
 26–3061 (20–86)41 (7–74)41 (7–74) 
 >3066 (32–86)53 (19–78)53 (19–78) 
Group 2   0.011
 <2089 (64–97)83 (56–94)83 (56–94) 
 20–2583 (55–94)63 (29–84)50 (18–76) 
 26–3073 (37–90)73 (37–90)73 (37–90) 
 >3053 (31–72)37 (16–57)29 (11–51) 

There was no difference in the overall survival among the different etiologies (chronic rejection, hepatic artery thrombosis, recurrent primary sclerosing cholangitis, or other) for reTX within group 2. Neither recipient gender, race, nor age was significant predictors of post-reTX survival in either group 1 or 2. In group 2, reTX survival was worse in those retransplanted <1 yr from initial transplant compared to those retransplanted 1–3 yr and >3 yr from primary transplant. (3-yr survival: <1 yr, 46%; 1–3 yr, 80%; >3 yr, 70%) Retransplant survival difference based on time from initial transplant was not noted in group 1.

Multiorgan failure was the most common cause of death in group 1, whereas sepsis was the overwhelming cause of death in group 2 (Table 5). The causes of death in those who survived greater than 1 yr in group 1 was recurrent HCV (2 patients), recurrent hepatocellular carcinoma (1 patient), viral sepsis (1 patient), and multiorgan system failure (1 patient). In group 2, the causes of death after the first year were multiorgan system failure (3 patients), other causes (3 patients), cardiac disease (2 patients), recurrent hepatocellular carcinoma (1 patient), and bacterial infection (1 patient).

Table 5. Causes of Death
Cause of deathHCV reTX n = 17Non HCV reTX n = 29HCV No reTX n = 86
N (%)N (%)N (%)
  1. Abbreviations: MOSF, multiorgan systemic failure; HCC, hepatocellular carcinoma.

Recurrent HCV (liver failure)2 (11)0 (0)38 (44)
MOSF5 (29)8 (28)26 (32)
Sepsis, bacterial1 (6)10 (34)5 (6)
Sepsis, fungal1 (6)2 (7)0 (0)
Sepsis, viral1 (6)1 (3)2 (2)
Hepatorenal2 (11)0 (0)3 (4)
Cardiac1 (6)3 (10)1 (1)
Pulmonary0 (0)0 (0)2 (2)
HCC1 (6)1 (3)1 (1)
Bleeding1 (6)3 (10)1 (1)
Chronic rejection2 (11)0 (0)0 (0)
Tumor, other0 (0)1 (3)7 (8)

Analysis of Patients With Recurrent HCV Not Retransplanted

A large number of patients (156) with graft failure due to histologically confirmed recurrence of HCV were not retransplanted during this study period. These patients developed graft dysfunction defined by decompensated liver disease. Only 46 of 156 (30%) patients were reevaluated for reTX. Furthermore, only 24 of 46 (52%) of these patients were placed on the waiting list for reTX; 19 of these 24 patients died prior to the opportunity for reTX, and 5 were still on the waiting list at the time of the study. Characteristics of patients with graft failure due to recurrence of HCV who were and were not retransplanted is provided in (Table 2). However, this group of patients was predominately males (71%) in contrast to the retransplant groups that had equal gender distribution.

Overall survival in this group of patients was poor (1 yr: 70%; 3 yr: 40%; and 5 yr: 22%). The causes of death were liver failure from recurrent HCV (44%), multiorgan failure (32%), and tumor (8%) (Table 5).

The main reasons for not listing for reTX were: recurrent HCV within 6 months of transplantation (22%), fibrosing cholestatic HCV (19%), renal dysfunction [serum creatinine >2 mg/dL (9%) and hepatorenal syndrome (9%)], and “other” (28%) (age >60 yr, infection, patient request, noncompliance, low MELD score, and single cases of aortic stenosis, uncontrolled gastrointestinal bleeding, intracranial hemorrhage, and unknown).

Days of Hospitalization and Intensive Care Unit (ICU)

Days of hospitalization were similar among groups 1 and 2 after the first and second transplantation (first transplantation, median days ± standard deviation, 9 ± 4 [6–172] vs. 15 ± 2 [6–68]). The length of stay was about 1 week longer at reTX (second transplant, median days ± standard deviation, 13 ± 4 [3–105] vs. 19 ± 3 [1–90]). Interestingly, ICU days were similar among groups and transplants (first transplant, median days, 2 ± 0.5 [1–22] vs. 3 ± 0.5 [1–10]; second transplant, median days 3 ± 2 [1–70] in both groups). In group 1, 21 (49%) patients were hospitalized at the time of reTX and 4 (9%) were in the ICU. Whereas in group 2, 36 (49%) were hospitalized at time of reTX and 13 (18%) patients were in the ICU. Only 1 patient was on a ventilator at reTX in group 1, while 4 patients in group 2 were on a ventilator. A higher percentage of patients in group 2 than in group 1 were on dialysis at reTX, 20% vs. 11% in group 1. Despite more patients in group 2 being in the ICU and in renal failure, overall survival was similar to group 1. When patients that were in the ICU or on dialysis were excluded (in both groups), survival was again similar (1-yr and 3-yr survival: group 1, 75% and 53% vs. group 2, 84% and 73%; P = 0.35).

DISCUSSION

This is the first multicenter U.S. study examining reTX with histological confirmation for the etiology of initial graft failure and need for reTX. We also report the frequency and fate of patients with graft failure due to recurrence of HCV who are not listed for reTX. The most important finding of our analysis is that overall 1-yr and 3-yr survival rates are similar for patients retransplanted for recurrent HCV when compared to patients undergoing reTX who do not have HCV infection. However, overall reTX survival is poor. Inspection of the patients who were retransplanted revealed that they were highly selected patients, as noted by the majority of patients (67–81%) being calculated as low-risk patients by prior retransplant survival models. Therefore, these results should not be extrapolated to all patients with recurrent HCV or other causes of graft failure requiring reTX. The message should be that appropriately-selected patients for reTX regardless of cause will result in acceptable results. This study also found that a large proportion (30%) of patients with graft failure due to recurrent HCV infection are not considered for reTX and only half of those who are evaluated are relisted. Furthermore, of those patients who were relisted, most died (79%) while awaiting reTX.

Overall post-reTX survival in this study was similar to that reported in previous studies of registry databases (United Network for Organ Sharing or Scientific Registry of Transplant Recipients).6, 9, 10, 14 The advantage of this study was that the pathological confirmation of graft failure was available, which is not available in large database resources. Several single-center studies have noted slightly higher survival than reported by our group.18, 21–23 The reported ability of MELD scores to predict post-reTX survival has been variable.9, 24–27 In our study, although MELD scores were not predictive of post-reTX survival, higher MELD scores (particularly >25) at the time of reTX were associated with high post-reTX mortality. Overall post-reTX patient survival at 3 yr was 40 to 56% for patients with HCV infection regardless of MELD scores, whereas in non-HCV patients, the survival at 3 yr was below 60% only when the MELD score was above 30 (survival was 37%). Not surprisingly, the MELD scores in all groups of patients rose from first transplantation to second listing to second transplantation. Interestingly, patients with recurrent HCV who did not undergo reTX had the highest MELD scores at the time of evaluation for reTX, potentially reflecting a group of sicker patients predicted to have a much poorer outcome.

Our study was not designed to identify variables that might predict reTX survival. However, analysis of several variables that previously were associated with poor survival (etiology for reTX in group 2, recipient age, gender, race, and donor age) were not predictive. Time interval from initial transplantation to reTX was a predictive of survival in group 2 patients, but not in group 1. Those retransplanted within 1 yr of initial transplant had poorer survival (3-yr survival, 46%). Other studies have found many variables that may contribute to poorer survival including recurrent HCV,14 Child-Turcotte-Pugh score,25 hepatic encephalopathy,25 intensive care stay,14, 28 poor renal function,14, 19, 20, 22, 25, 29, 30 donor age,11, 14, 17, 20, 27 prothrombin time,11, 20, 25 time interval from initial transplantation,14, 27 recipient age,14, 20, 22, 25, 27, 30 ventilatory status,6, 20 bilirubin level,6, 14, 19, 20, 22, 29, 30 physical condition,31 and intraoperative blood loss.22, 30 Interestingly, many patients in this study had isolated variables or poor outcomes (51% had bilirubin >10 mg/dL and 25% had serum creatinine > 2 mg/dL). This topic has been extensively reviewed and studied before; nevertheless, many predictive models have used elaborate mathematical formulas that are not easily used or have variables that are not available prior to the reTX.19, 20, 28 In contrast to primary transplantation, the decision whether to retransplant a patient focuses on post-reTX survival. Whereas, pretransplant mortality (MELD score) is the principal driving force for primary transplantation. An interesting perspective was reported by Burton et al.,26 using a model of maximizing utility. They found that a MELD score of 21 for HCV patients and 24 for non-HCV patients maximized this limited resource. In addition, these same investigators surveyed U.S. transplant programs and found that HCV alone was not a contraindication for reTX. Variables of more concern were recipient age greater than 60 yr and early cirrhosis (<2 yr).16

Evaluation of patients with recurrent HCV who were not relisted for reTX revealed that the number of patients were 3 times greater than those who did get retransplanted. A fear of worse outcomes after reTX for patients with recurrent HCV undoubtedly may have resulted in fewer numbers of these patients being selected for reTX. Only 30% of patients with allograft failure from recurrent HCV were evaluated for reTX. Furthermore, only 16% of the 156 patients not getting retransplanted were ever listed for reTX, with the majority of those patients dying prior to the opportunity to be retransplanted. Therefore, very few recurrent HCV patients are being retransplanted. Our data shows that <1% of transplants in these centers are being done for recurrent HCV graft failure. Perhaps clinicians may have learned, from prior studies and experience, which patients should be excluded from reTX. Those patients that do get retransplanted for recurrent HCV, therefore, are a very highly-selected group of patients. Thus, this could impact the results of our study. However, listing and when to evaluate patients for transplantation is the art of medicine, and no uniform guidelines exist, especially when considering reTX. Not surprising, the most common reasons for not relisting were early recurrent HCV after the initial transplantation and/or renal dysfunction.

Studies have used various models to predict post-reTX outcomes,19, 20, 28, 31 but these models are not easily calculated and many of the variables are not available at the time of reTX evaluation (i.e., cold ischemia time, donor age, intraoperative blood loss). MELD scores have been shown in other studies to predict posttransplantation survival.9, 19, 24, 25, 28 In our study it was not predictive of survival in HCV patients partially due to low (3 yr) survival even in the moderate MELD score range.20–25 Given the mean MELD score >25 at the time of evaluation for reTX, it is not surprising that these patients were often not offered a retransplant or could not survive long enough to get the organ they needed.

The days of hospitalization and ICU stay have changed from an earlier study,27 but were similar to a more recent study.27 About half the patients were in the hospital at the time of reTX, with only a few in the ICU or on mechanical ventilation. Renal failure was not uncommon (10–20%) at reTX. Hemodialysis and ventilation support were less common at the time of reTX in the HCV than non HCV infected group. This likely reflects the education of physicians from earlier studies and the practice of selecting patients who are not considered to be futile candidates for reTX.32

The suggested use of extended grafts or living related donor transplantation may have a role in improving reTX, but has rarely been discussed. No retransplant patient in our study received a living donor liver transplant, likely due to concern for a high-risk recipient receiving a higher-risk operation. Extended donors were not overly used for reTX. Survival was better for lower MELD scores; thus, should patients be allocated additional MELD points to improve post-reTX outcomes? This is a difficult question, as reTX inherently has a 20% lower patient survival; therefore, institution of such a policy could potentially reduce overall transplant survival. The ethical implications in reTX are many and diverse, especially with limited organ availability.33 However, many believe that the minimal survival after reTX should be equivalent to the lowest primary transplantation. Therefore, recipients who are older, and have severe renal dysfunction and high MELD score (>30), are poor candidates for reTX, regardless of the presence of HCV infection. Recurrent HCV in isolation is not a contraindication for reTX; rather, all variables should be used to evaluate a potential candidate.

Ancillary