Objectives: Liver transplant for alcoholic liver disease requires identifying potential recipients at risk for recidivism. We sought to identify risk factors for recidivism and survival in recipients of liver transplant with alcoholic liver disease.

Materials and Methods: Demographic, psychosocial, and histology features were evaluated as risk factors toward harmful recidivism in 148 recipients of liver transplant with alcoholic liver disease.

Results: Based on the univariate analysis using Cox proportional hazards model, duration of alcohol abstinence 6 ≤ months (HR 3.74; P = .011, 95% CI: 1.36-10.3), non-alcohol related criminal history (HR 3.18; P = .032, 95% CI: 1.1-9.15), support from immediate family (HR 0.24; P = .0061, 95% CI: 0.09-0.67), and active smoking at the time of liver transplant (HR 2.74; P = .041, 95% CI: 1-7.53) were identified as significant predictors for recidivism. Older patients had less likelihood of alcohol relapse (HR 0.91; P = .0014, 95% CI: 0.87-0.97) on univariate model. In multivariate model older patients (HR 0.91; P = .004, 95% CI: 0.86-0.97) and patients who have immediate family support (HR 0.27; P = .012, 95% CI: 0.10-0.76) predicated against recidivism. Suggestive features of alcoholic hepatitis on liver explant did not predict recidivism or long-term survival. One-, three-, and five-year patient survival rates estimated by Kaplan-Meier survival model in the recipients that remained abstinent were 95%, 87%, and 80%, compared with 87%, 49%, and 49% for the recipients with recidivism (P = .001).

Conclusions: Recidivism is associated with earlier death after liver transplant. Older recipients and patients with immediate family support are less likely to have alcohol relapse, and have better long-term survival.

Key words : Disease recurrence, Survival analysis, Rehabilitation, Liver disease

Introduction

Liver transplant for alcoholic liver disease continues to generate controversy, particularly with its recommended 6 months of abstinence before liver transplant. In a review of 22 studies on alcoholic liver disease, relapse ranged from 3% to 49%, with graft dysfunction and death ranging from 0% to 27% and 0% to 6.5%.¹ Therefore, it is essential to accurately identify patients before liver transplant who are likely to relapse to harmful drinking after the transplant.

Data on relapse of alcohol abuse with a minimum of 6 months of abstinence before liver transplant are conflicting.^2-4 Several other factors have been identified as predictors for recidivism; however, none has been reliable and consistent across studies.^1-4 Further, a recent French study has provided encouraging data on the outcome after liver transplant in alcoholic hepatitis patients who failed to respond to corticosteroids, challenging the 6-month rule of alcohol abstinence before liver transplant.⁵ However, this study from France had a relatively short posttransplant follow-up of only 2 years. Another recent retrospective US study, using the United Network for Organ Sharing database to assess the 5-year post-liver transplant graft and patient survival of patients with alcoholic hepatitis compared the results with patients transplanted for alcoholic cirrhosis and found no significant difference in graft or patient survival.⁶

There is a need for more studies that address factors associated with recidivism and to separate patients who remain abstinent and benefit from liver transplant from patients who will return to alcohol use and place their graft and/or lives at risk for loss. We sought to identify risk factors for recurrent alcohol consumption after orthotopic liver transplant, the effect of 6-month abstinent rule on recidivism, and long-term outcomes after liver transplant.

Materials and Methods

There were 686 adult liver transplants performed at out center between January 1, 2006, and December 31, 2011. A retrospective review was performed with Institutional Review Board approval from the University of Tennessee Health Science Center to identify adult liver transplant recipients with an indication for alcohol-related liver disease. The diagnosis of alcohol-related liver disease was based on compatible history, laboratory, and/or histologic data by physician assessment and further supported by history of excessive alcohol consumption with both dosage and duration confirmed by an independent evaluation with transplant social worker. These evaluations are documented in the medical record. Additionally, the evaluation includes use of rehabilitation programs or substance abuse abstinence support programs, past and current history of tobacco use, additional recreational or abusive drug use, criminal history, drug or alcohol-related arrests, psychiatric illnesses and treatments, and assessment of posttransplant support structure. Support is defined as acknowledgement and agreement by committed family members or friends or other persons who will help the patient with transportation, medication supervision, and activities of daily living for a smooth transition to independence. Patients with coexisting causes for cirrhosis were not excluded if excessive alcohol abuse was determined to be a significant contributor to end-stage liver disease.

In general, patients were required to be abstinent for at least 6 months and to enroll in counseling or support services if deemed necessary by the transplant center. The date of alcohol abstinence is verified by the social worker based on multiple sources by self-report by the patient, confirmation by family members, and documentation by the referring physicians. Additionally, at the Methodist University Hospital Transplant Institute, all patients were required to a sign a contract to remain abstinent after the liver transplant. In cases where the exact time of abstinence was unclear, the date of this contract was used as the initial day of abstinence. If a patient with severe liver decompensation was believed to have probable survival less than 6 months and the transplant center and psychosocial evaluation believed that there was a low risk for recidivism, then the patient could still be listed for transplant.

One hundred sixty-one patients with alcohol-related liver disease were identified who underwent liver transplant. Patients that died within 3 months of the liver transplant were excluded. This exclusion was to remove patients with postoperative com­plications that lead to an early death, and it was unlikely that a return to alcohol use would occur in the first 3 months after the liver transplant. Additionally, patients requiring retransplant were followed from the time of the first transplant, provided survival was more than 90 days. Graft failure was defined as allograft dysfunction leading to death or retransplant.

Liver transplant recipients were seen by protocol in the clinic every 2 weeks for the first month, each month at months 2 and 3, every 3 months for the remainder of the first year, and every 6 months for the second year, and then annually beginning with the third year. Additionally, laboratory studies were performed by protocol with the following schedule: weekly for the first 3 months, every 2 weeks for months 4 through 6, monthly for months 7 through 12, and every 3 months beginning the second posttransplant year. Exceptions that include more frequent evaluation for both clinic visits and laboratory schedules are made based upon clinic status.

Patient charts were reviewed to obtain demo-graphic variables (including age at transplant, gender, and race), medical acuity of liver disease at the time of transplant by Model for End-stage Liver Disease (MELD) score, history of smoking, history of additional substance abuse, insurance coverage, employment status, highest level of education, psychiatric comorbidities, social support after transplant, type of community, distance to the transplant center, criminal history, history of driving under of influence, and length of abstinence from alcohol before liver transplant. Pretransplant abstinence was defined as the time between the last consumption of alcohol to the date of transplant. Recidivism to harmful alcohol use after liver transplant was defined as a return to frequent consumption of alcohol and/or consumption of alcohol associated with medical or social harm, and it was identified by patient self-reporting, family reporting, presentation to a medical facility, and/or compatible laboratory or histologic findings.

Statistical analyses
Descriptive statistics were calculated for all of the key variables. Continuous variables were expressed as mean with standard deviation and categorical variables as counts with percentages. Time to alcohol relapse was calculated from the date of transplant to the date of alcohol relapse and those who did not have relapse were censored at their last contact date. Similarly, time to death was calculated from the liver transplant date to the date of death and those who were still alive were censored at their last contact date.

The Kaplan-Meier method was used to estimate alcohol relapse-free survival (RFS) and overall survival (OS) and log-rank test was used to compare the RFS and OS distributions at the levels of a given demographic and clinical factor of interest. Cox proportional hazards models were constructed to investigate the association of RFS and OS with a variable or a group of variables. In multivariable survival models, we kept in mind the "10 event per covariate" recommendation^7,8 to decide how many predictors can be supported in such models. This is a retrospective study and P values reported in this study are not adjusted for multiplicity; therefore, the findings must be considered in the hypothesis generating context and confirmed with larger prospective studies. All statistical analyses were performed with SAS Version 9.4 (Cary, NC, USA).

Results

Patient demographics and medical status
Of the 161 recipients with alcohol-related liver disease, 13 patients were excluded because of patient survival of less than 3 months postoperatively. Demographic and clinical characteristics for the 148 patients in the study are presented in Table 1. The mean age was 54.0 ± 8.3 years old. The majority was male 128 (86.5%) and white 106 (71.6%). Twelve patients received simultaneous liver-kidney transplant. Alcohol-related liver disease alone was the indication in 92 recipients (62.2%). Concurrent indications were classified as: chronic hepatitis C in 28 patients (18.9%), hepatocellular carcinoma in 18 patients (12.2%), chronic hepatitis C with hepatocellular carcinoma in 4 patients (2.7%), chronic hepatitis B in 2 patients (1.4%), hemochromatosis in 2 patients (1.4%), Caroli disease with hepatocellular carcinoma in 1 patient (0.7%), chronic hepatitis C with alpha-1 antitrypsin deficiency in 1 patient (0.7%). The mean MELD score of the recipients was 22.3 ± 7.0. Some form of psychiatric treatment was instituted in 38 recipients (26.6%) before undergoing liver transplant.

Social characteristics
The mean distance from living quarters to the transplant center was 132 ± 136 miles with 82 of the recipients (55.4%) living in an urban area. The highest educational level achieved was some high school credit in 29 recipients (19.6%), high school graduation in 56 recipients (37.9%), some college credit in 31 recipients (21.6%), and college graduation in 59 recipients (39.9%). Twenty-four (16.2%) had full-time employment, 5 (3.4%) were working part-time, 59 (39.9%) were receiving disability payment, and 60 (40.5%) were unemployed or retired at the time of transplant. Of those recipients that were employed, 41(27.7%) were in white collar jobs. Health care insurance status for the recipients was private insurance in 78 (52.7%), Medicare in 45 (30.4%), Medicaid in 16 (10.8%), and other in 9 (6.1%). Non-alcohol related criminal history was noted in 19 recipients (12.8%).

Characteristics related to alcohol, tobacco, and other substance uses before transplant were also evaluated. The duration of abstinence was ≤ 6 months in 21 (14.2%) and > 6 months in 127 (85.8%) of the 148 patients with the mean duration of alcohol abstinence before their liver transplant being 36.8 ± 66.4 months. Twenty-three recipients (15.5%) had a prior alcohol-related arrest such as driving under the influence. Twenty patients (13.5%) attended Alcoholics Anonymous or a similar support group before transplant. Current tobacco smoking was reported by 27 recipients (18.2%), and 55 recipients (37.2%) had a previous history of tobacco use but had quit before transplant. Fifty-six recipients (37.8%) had prior substance abuse aside from alcohol or tobacco.

Posttransplant social support was also evaluated. One hundred three recipients (69.6%) had support from an immediate family member such as spouse, parent, or child, and 32 recipients (21.6%) were supported by an extended family member. Nine recipients (6.1%) were supported by friends, and 4 (2.7%) had support from other individuals or services.

Explant histopathology
Five characteristics seen on the explanted hepatectomy specimen that may be related to recent heavy consumption were also evaluated: steatosis, foamy degeneration, ballooning degeneration, mega mitochondria, and Mallory-Denk bodies. Steatosis > 5% was seen in 31 specimens (21.0%). Twenty-four specimens (16.2%) had hepatocytes with foamy degeneration, and 14 (9.4%) had hepatocytes with ballooning degeneration. Well-defined Mallory-Denk bodies were seen in 6 (4.1%) of the explanted livers. Mega-mitochondria were seen in 8 specimens (5.4%). The presence of at least 3 histologic characteristics was defined as alcoholic hepatitis. Based on these criteria, 15 patients (10.1%) had evidence for alcoholic hepatitis in the explanted liver. All the explanted liver showed features of cirrhosis of the liver, with bland cirrhosis, defined as no histologic evidence of any of the identifiable features of active alcoholic liver disease, was noted in 32 patients (21.6%).

Recidivism, predictors, and outcomes
A total of 16 (10.8%) went into harmful alcohol consumption after their liver transplant. Eleven of the sixteen patients had recidivism within the first year posttransplant.

Duration of alcohol abstinence 6 ≤ months (HR 3.74; P = .011, 95% CI: 1.36-10.3), non-alcohol related criminal history (HR 3.18; P = .032, 95% CI: 1.1-9.15) and support from immediate family (HR 0.24; P = .0061, 95% CI: 0.09-0.67), and active smoking at the time of LT (HR 2.74; P = .041, 95% CI: 1-7.53) were identified as significant predictors for recidivism (Table 2). The Kaplan-Meier estimate of the RFS distributions and the corresponding Log-rank test results were presented in Figures 1-4 for these factors. Age at transplant was also significantly associated with the likelihood of alcohol relapse, where older patients had less likelihood of alcohol relapse (HR 0.91; P = .0014, 95% CI: 0.87-0.97). Variables such as gender, race, MELD score, psychiatric history, distance from living quarters to the transplant center, level of education, employment status, job type, alcohol-related arrest, participation in support group, past tobacco use, prior substance abuse, and histopathology features had no effect on recidivism (Table 2).

Considering that there are 16 events (recidivism) for alcohol relapse-free survival, a multivariable model for overall survival can support up to 2 predictors. As criminal history and immediate family support was found to be highly correlated (Fisher exact test; P = .023), immediate family support was chosen as a predictor in the model. The variable duration of alcohol abstinence ≤ 6 months is also significantly associated with immediate family support (Fisher exact test; P = .023) and lost its significance when we modelled it along with "immediate family support" (P = .061); therefore, we chose not to include it in the final model. Hence, age and immediate family support were chosen as the predictors in the final model. As noted in Table 3, older patients (HR 0.91; P = .004, 95% CI: 0.86-0.97) and patients who have immediate family members to support (HR 0.27; P = .012, 95% CI: 0.10-0.76) are significantly less likely to have recidivism.

Twenty-nine of the 148 recipients (19.6%) transplanted with an indication including alcohol-related liver disease died during a mean follow-up of 1354 ± 669 days (range, 104-2594 d). The cause of death is summarized in the Table 4. Eight of the 16 LT recipients (50%) in the recidivism group died, and 11 of them had recidivism in the first year since their LT. Graft failure was noted in 3 recipients in the recidivism group, and 1 in the group without recidivism. Tylenol toxicity (n = 1), failure to thrive (n = 1), acute myocardial infarction (n = 2), and sepsis (n = 1) were other causes, all of which appeared to be directly or indirectly related to recidivism. Twenty-one of the deaths (15.9%) occurred in the group without recidivism, with sepsis being the most common cause (n = 7).

The mean duration of survival of the patients who expired being 673 ± 401 days. As for RFS, we also investigated the association of overall survival of our cohort based on demographic and clinical factors. None of the variables except recidivism after LT (HR 3.74; P = .011, 95% CI: 1.36-10.3) were significantly associated with likelihood of death (Table 5). Considering there are 29 events (death) for OS, a multivariable model for OS can support up to 3 predictors. As noted in Table 6, recidivism after transplant was a significantly associated with 4-fold increased hazard of earlier death (HR 3.97; P = .001, 95% CI: 1.73-0.001) (Figure 5). Interestingly, history of no substance abuse before liver transplant (HR 2.41; P = .045, 95% CI: 1.02-0.04) was associated with increased hazard of death as well. The history of substance abuse, however, was remote, and these patients were younger compared to those who denied history of remote substance abuse (median age 52 vs 58; P = .0068).

Four of the 16 patients with recidivism were noted to be nonadherent to medications and clinical follow-up, and 3 of them expired. Acute cellular rejection was confirmed by liver biopsy was noted in 5 out of the 16 recipients and only 1 patient had medication nonadherence as the probable cause. Two additional patients were treated empirically for acute cellular rejection without biopsy due to clinical findings and history of noncompliance.

The 1-, 3-, and 5-year patient survival rates for the recipients that remained abstinent were 95%, 87%, and 80%, compared with 87%, 49%, and 49% for the recipients with recidivism (P = .001, Figure 5).

Discussion

In the current study we have critically analyzed factors associated with recidivism with particular emphasis on demographic, psychosocial, and histology features to identify patients at particular risk of returning to harmful consumption of alcohol posttransplant.

This study emphasizes the role of 6-month abstinence before liver transplant as an important determinant in predicting alcohol relapse-free survival after transplant. Our transplant center generally adopts the 6-month abstinence rule; however, a significant consideration is also given to their other psychosocial factors, and some patients were transplanted despite not fulfilling their 6-month abstinence rule, if recidivism was considered less likely by the multidisciplinary committee based on comprehensive assessment of other psychosocial factors. In the current study, 21 of the 148 recipients (14.2%) remained abstinent for less than 6 months before their transplant; 6 of the 21 recipients (28.6%) who remained abstinent for the less than 6 months had documented recidivism compared to 10 of the 127 (7.9%) with more than 6 months of abstinence.

The 1-, 3-, and 5-year patient survival rates for the recipients that remained abstinent were 95%, 87%, and 80%, compared to 87%, 49%, and 49% for the recipients with harmful recidivism (P = .001) (Figure 5). The poor survival in recipients with harmful alcohol abuse in our cohort might be related complications that can be attributed as a direct or indirect consequence of their return to harmful alcohol drinking. Poor long-term survival that can be directly attributed to recidivism has been reported in an earlier study when subjects returned to abusive or harmful alcohol drinking, although another study with longer follow-up attributed this to increased prevalence of cancer and cardiovascular events.^9-11 Differences in the actual rate of survival could be related to the time of recidivism since liver transplant, noncompliance to follow-up, nonadherence to immunosuppressive medications leading to acute cellular rejections, sociocultural differences in the recipients, and possibly definitions used with regard to recidivism (any alcohol consumptions versus harmful alcohol abuse). Regardless of contributing factors, all studies share poor long-term survival in recipients with recidivism.

Although some studies have considered the 6-month abstinent rule as being too stringent with high wait time mortality, the current study again emphasizes the continued role of 6-month abstinence as a strong predictor for alcohol relapse, as well as having a suggestive negative impact on patient survival.^2,12,13

Older age at transplant also appeared to be a predictor for maintaining abstinence from alcohol consumption after a liver transplant. In fact, the recipients of liver transplant who returned to alcohol consumption posttransplant were almost 8 years younger than those recipients that remained abstinent (47.6 ± 12.1 vs 54.5 ± 7.5; P = .033). Presumably, the propensity for higher-risk behaviors in younger, less mature patients may influence their return to alcohol consumption. It is known that rates of alcohol abuse and dependence are disproportionately higher among young adults compared with other age groups. Most heavy-drinking young adults appear to "mature out" of abusive drinking patterns as the responsibilities such as marriage, career development, and child-rearing become important.¹⁴ In fact, a recent study suggested that individuals with alcoholism are more likely have a lower self-perception of majority as they move into middle age than individuals without alcohol use problems.¹⁵ Although this should not mean that younger patients should be denied liver transplant; rather, they need to be more stringently monitored during their posttransplant period and might benefit from structured posttransplant alcohol rehabilitation and support program such as Alcoholics Anonymous.

Pretransplant tobacco use was associated with poor alcohol relapse-free survival in the post-transplant period, and the association being particularly significant in those with active smoking. However, based on the small number of events for RFS, we did not have sufficient statistical power to include a third variable; therefore, we were unable to investigate the current smoking status in our final multivariable model. Nevertheless, those who are active smokers at the time of transplant had much worse RFS in univariable analysis as shown in Figure 2. Multiple studies indirectly suggest that continued smoking may place alcohol-dependent smokers at risk for alcohol relapse.¹⁶ It is possible that conditioning, which is one stimulus resulting in associated behavior or effect being paired with a second stimulus to bring a similar behavior or effect, plays a role in these cases. Conditioning factors associated with tobacco use may increase cues toward alcohol because of experiences that have associated the 2 substances.¹⁷ In our center, it is policy to strongly encourage smoking cessation in transplant candidates in light of the association with alcohol use as well as other negative health consequences.^18-20 Meta-analysis demonstrated that at long-term follow-up, participation in a smoking cessation intervention provided during substance abuse treatment was associated with long-term abstinence from alcohol and other drugs.²¹ Consistent with these findings, data suggest that 1 year after treatment, smokers who participated in a substance abuse treatment program and initiated smoking cessation on their own were less likely to be diagnosed as alcohol dependent and had more days abstinent from alcohol and other substances than those who started or continued smoking during the follow-up.²² Thus, smoking has a direct negative health consequence that affects long-term survival in any transplant recipient, and it possibly plays a role in returning to alcohol consumption in recipients transplanted for alcoholic liver disease based on the current study.

Having the support of a spouse, parent, or child to aid posttransplant recovery was protective against recidivism. It may relate to the strength of the relation as well as the impact of both the alcoholism and liver disease on the potential loss of the relation. Evaluation of the support system is an important part in the evaluation of the patients' transplant candidacy, and its importance has been well reported.²³

We evaluated various other high risk traits or situations generally associated with alcohol consumption including history of psychiatric comorbidities, use of other substances abuse, criminal history, and driving under the influence. Alcohol relapse-free survival also was poor in recipients with non-alcohol related criminal history by Kaplan-Meier survival analysis, but it was significant only on univariate Cox proportional hazard model but not on multivariate analysis. The nature of the relation between alcohol and crime has several themes including a direct relation to violence, an increase in violent behavior to obtain more alcohol, and environmental and genetic factors that contribute to violent behavior. ²⁴

Interestingly in our cohort, LT recipients with remote history of substance abuse have better overall survival. This likely reflects our stringent practice of patient selection of recipients with history of substance abuse over alcohol abuse. In our practice, we require LT recipients to demonstrate a lengthy period of cessation before listing for LT. We suspect these LT recipients are more reformed "past drug abuser," reflecting less likelihood of posttransplant substance abuse, and better long-term survival. Prior history of remote substance abuse, however, did not have any effect on alcohol relapse free survival in our cohort. We also require that patients with significant history of psychiatric disorder including depression are well treated before they are considered for transplant. Interestingly, we did not find any significant reduction in recidivism in patients who attended counseling or support groups including Alcoholics Anonymous, although this is strongly recommended to all subjects considered for transplant with an indication of alcohol-related liver disease.

Finally, we wish to underscore that in this sample, insurance coverage, employment status, highest level of education, type of community, and distance to the transplant center did not predict outcome either in univariate analysis or after adjustment for other variables.

Analysis of the explant histopathology for evidence of active alcohol consumption was not useful in predicting return to alcohol consumption following liver transplant. In the current study, we also analyzed multiple individual histological variables, such as presence of steatosis, well-defined Mallory-Denk bodies, mega-mitochondria, ballooning degeneration, and foamy degeneration were not seen in patients that showed recidivism toward drinking alcohol. Neither histologic evidence of alcoholic hepatitis nor bland cirrhosis was a predictor of recidivism. This finding is similar to a previous study that specifically looked into posttransplant alcohol relapse based on histologic alcoholic hepatitis on explant specimen where the presence of histologic alcoholic hepatitis was not predictive of relapse or worse long-term outcome.^25,26 Based on this study and analysis from our center, we do not recommend liver biopsy before listing patients with alcohol-related liver disease for liver transplant to guide decision-making on their risk for drinking posttransplant.

Our analysis also demonstrated that survival was significantly worse in recipients with recidivism after their liver transplant compared to recipients that maintained abstinence. Thirty-three patients had concomitant hepatitis C virus (HCV) infection con-tributing to their liver disease (Table 1). Histologic recurrence of HCV was noted in 20 recipients (60.6%) with only 1 patient progressing to cirrhosis during the follow-up; this patient was still alive at the time of this analysis. Of the 20 recipients with recurrent HCV, 3 recipients (15%) died, but none of the deaths was related to graft failure from recurrent HCV. There were no significant difference in the number of death in the HCV and the non-HCV group (6 [18.25%] vs 23 [20%]; P = .817). Recurrence of hepatitis C had no effect on alcohol relapse-free survival as well as overall survival (Table 2 and 5) in recipients of alcoholic liver disease with concomitant hepatitis C.

The limitations of the current study are those inherit to any retrospective, single-center study. The selection criteria are center specific and introduce a bias which may limit wider applicability to other centers. However, single center analysis does provide some clarity to certain variables that may not be captured in large registries. In this particular study, variables identified to effect recidivism toward alcohol consumption (age, abstinence period, and current tobacco use) can be used by other centers when drafting criteria for candidates to be placed on the waiting list for liver transplant with an indication of alcohol-related liver disease. Additionally, the level of support and non–alcohol-related criminal history, although not independently predictive, also can be included in this difficult, but imperfect, decision-making process. It is important to place all demographic data, psychosocial factors, and clinical parameters into the appropriate context to assure the best outcome. However, retrospective review of medical records likely underestimates the true prevalence of recidivism. Prospective studies with emphasis on clear assessment of risk factors already identified and validated assessment tools of alcohol use and relapse might help strengthen the conclusions.

In conclusion, young patients, patients with short duration of abstinence (≤ 6 months), and those who are actively smoking, and those who had history of non–alcohol-related criminal history, if considered for liver transplant for alcohol-related liver disease, potentially may benefit from a structured pre-and posttransplant rehabilitation or counseling prog-rams.27 Older recipients, and those with immediate family support are less likely to have harmful recidivism. Additionally, liver histopathology findings of alcoholic hepatitis does not have any role in the decision to consider these patients for liver transplant and should not be used to exclude otherwise suitable candidates from being placed on the waiting list.

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