Impact of the MELD score on waiting time and disease severity in liver transplantation in United States veterans

Authors


Abstract

Organ allocation for liver transplantation (LT) in the United States is based on the Model for End-Stage Liver Disease (MELD) score. The MELD score prioritizes organ distribution to sicker patients. There is limited data on the effect of this policy on transplantation in the Veterans Affairs (VA) healthcare system. The aim of this study was to determine the impact of the MELD score on U.S. veteran patients undergoing LT. Comparison of MELD scores and waiting time of LT recipients before and after the introduction of the MELD system was done. A total of 192 LT recipients were analyzed. Blood type, diagnosis, listing MELD score, and Child-Turcotte-Pugh (CTP) score at transplant did not differ although MELD era recipients were older (mean 54.3 vs. 51.3 yr, P = 0.009). Mean waiting time decreased from 461 days (pre-MELD) to 252 days (MELD era) (P = 0.004). Mean MELD score at LT increased from 23.4 (MELD era) compared to 20.3 (pre-MELD) (P = 0.01). In conclusion, waiting time for LT in U.S. veterans has decreased significantly in the MELD era. The MELD score of patients transplanted in the MELD era is significantly higher and patients are still being listed at a high MELD score. The MELD system has lead to sicker veterans being transplanted with shorter waiting times. Liver Transpl 13:1564–1569, 2007. © 2007 AASLD.

The burden of chronic liver disease in the U.S. veteran population is higher than that in the nonveteran population, often due to hepatitis C (HCV). A recent study demonstrated a prevalence of anti-HCV antibody in users of U.S. Veterans Affairs (VA) medical centers of 5.4%,1 3 times the level seen in the general population.2 Veterans with HCV often have advanced disease at presentation3 and treatment is usually not very successful.4, 5 The annual incidence of new cases of HCV infection has fallen with screening of the blood supply6 and safer practices among injection drug users but the long latent phase means more patients with chronic HCV and cirrhosis are now presenting.7

Liver transplantation (LT) is the standard therapy for most patients with end-stage liver disease but a lack of deceased-donor organs limits its effectiveness. Organ allocation used to be based on a system consisting of waiting time, geography, and several subjective measures of medical urgency, including the Child-Turcotte-Pugh (CTP) score. This led to discrepancies in waiting time across geographic regions.8 Hence, the U.S. Department of Health and Human Services issued “the final rule” regulation in 1998, which stated that the allocation of donor livers should be based primarily on medical urgency and less emphasis placed on geography.9 As a result, the Model for End-Stage Liver Disease (MELD) score was adapted and since February 2002 has been used as the basis for the adult liver allocation system for patients with chronic liver disease in the United States. The MELD score accurately predicts 3-month mortality among patients with chronic liver disease on the waiting list10 and was implemented to prioritize organs for sicker patients and reduce the waiting list mortality, without reducing posttransplant survival.

There is limited data on LT in the veteran population. A recent study suggested a higher mortality in veterans undergoing LT compared to nonveterans,11 and earlier studies have shown this is related to an increased number of high-risk recipients.12 However, this was based on patients undergoing LT prior to the introduction of the MELD score.

The aims of the present study were 2-fold. First, to determine if the implementation of the MELD score has led to veteran patients with more advanced disease undergoing LT, and second, has the implementation of the MELD score decreased the waiting time to LT in the veteran population.

Abbreviations

LT, liver transplant(ation); MELD, Model for End-Stage Liver Disease; VA, Veterans Affairs; HCV, hepatitis C; CTP, Child-Turcotte-Pugh; HCC, hepatocellular carcinoma.

PATIENTS AND METHODS

This study compared the MELD scores of patients transplanted in the VA Pittsburgh Healthcare System since the introduction of the MELD score in February 2002 (the MELD era) to a cohort of patients receiving transplantation in the preceding 6 yr, prior to the introduction of the MELD system (pre-MELD era). Several demographic factors including recipient age, race/ethnicity (white, black, Hispanic), blood type, and donor age were noted as well as CTP scores. The etiology of liver disease was categorized as follows: end-stage liver disease secondary to HCV, alcoholic liver disease, HCV and alcoholic liver disease, HCV and hepatitis B, and other liver diseases (cholestatic, autoimmune, fatty liver/nonalcoholic steatohepatitis, hemochromatosis, and cryptogenic cirrhosis).

Patients with hepatocellular carcinoma (HCC) receive special consideration under the MELD system since their liver disease is often not very advanced leading to a low MELD score and increased waiting list mortality.13, 14 Hence, patients with HCC are currently given a MELD score of 22 irrespective of their actual MELD score if they have stage II disease. This MELD score exception has changed several times since the advent of the MELD system with scores of 20 to 29 having been used depending on the stage of disease. To standardize the comparison between the 2 cohorts, patients who were known to have stage II HCC (single lesion greater than 2 cm and less than 5 cm, or 3 lesions the largest of which is less than 3 cm, and no evidence of vascular invasion on imaging or metastatic disease) prior to LT and who were given a MELD exception score were given a MELD score of 24. The calculated MELD score for these patients was also noted. Stage I HCC patients were not given a MELD exception and their calculated MELD score was used.

Patients with incomplete data, transplantation for acute liver failure, or second transplantation were excluded. MELD scores at the time of listing were calculated as well as MELD scores at time of transplantation. Waiting time was defined as the time from listing until LT.

To analyze the impact of the MELD system on waiting list deaths we noted the number of new patients added to the waiting list each year in the MELD and pre-MELD eras and the number of patients removed from the waiting list due to death or too sick to receive transplantation. Patients who were classified as status 7 (temporarily inactivated) at the time of death or being too sick to receive transplantation were noted.

We looked at outcome after transplantation by examining patient and graft survival. Kaplan-Meier curves were generated for the pre-MELD and MELD eras and compared using the log-rank test. Statistical analysis was carried out using Students' t test for continuous variables and the chi-squared test for categorical variables.

RESULTS

A total of 207 LTs were performed at the VAPHS between December 1995 and October 2005. A total of 83 transplants were performed in the pre-MELD era from December 1995 to February 2002 and 124 transplants in the MELD era from February 2002 until October 2005. A total of 15 patients were excluded, leaving 192 patients for the analysis. A total of 6 patients from the MELD era and 4 from the pre-MELD era were retransplantations and 5 patients from the pre-MELD era were excluded due to missing donor or recipient information.

Table 1 shows the baseline characteristics of the 192 transplantations analyzed. There was no difference between the 2 cohorts in terms of gender, race, blood type, or diagnosis, although transplant recipients and donors in the MELD era were significantly older. In the MELD era 25% of transplant recipients had HCC, vs. 8% in the pre-MELD era (P < 0.002). Evidence of HCV infection was present in two-thirds and significant alcohol use was involved in about one-half of all transplantations.

Table 1. Baseline Characteristics of 192 Patients Undergoing a First Liver Transplant Since 1995
 Pre-MELD era (n = 74)MELD era (n = 118)P value
  1. NOTE: All means are ± standard deviation (SD).

  2. Abbreviations: M, male, F, female; NS, not significant; HBV, hepatitis B virus; ABO, blood group.

Mean recipient age (years)51.3 ± 8.454.3 ± 5.70.009
Gender (M/F)74/0116/2NS
Race (%)   
 White8481NS
 Black711NS
 Hispanic98NS
ABO type (%)   
 A3836NS
 O4336NS
 B1418NS
 AB59NS
Diagnosis (%)   
 HCV2720NS
 Alcohol1221NS
 HCV/Alcohol3437NS
 HCV/HBV49NS
 Others2313NS
 HCC8250.002
Mean donor age (years)40.6 ± 16.544.5 ± 17.30.03

Table 2 shows the severity of liver disease at the time of listing and at the time of LT as measured by the MELD score. There was no difference in the MELD score at listing between the MELD era and pre-MELD era although there was a trend for patients to be listed at a higher MELD score in the MELD era. In addition, the CTP scores at the time of LT did not differ. However, the MELD score at the time of LT was significantly higher in the MELD era recipients compared to the pre-MELD era (23.4 vs. 20.3).

Table 2. MELD Scores and Waiting Time for 192 Patients Undergoing a First Liver Transplant Since 1995 Using Both MELD Score Exception and Calculated MELD Score
 Pre-MELD era (n = 74)MELD era (n = 118)P value
  1. NOTE: All values are mean ± standard deviation.

  2. Abbreviation: NS, not significant.

Transplant CTP score10.0 ± 1.810.2 ± 2.1NS
Listing MELD score (exception)17.7 ± 6.519.2 ± 7.5NS
Listing MELD score (calculated)17.0 ± 6.518.0 ± 7.7NS
Transplant MELD score (exception)20.3 ± 8.323.4 ± 6.10.01
Transplant MELD score (calculated)19.8 ± 8.320.7 ± 7.8NS
Waiting time (days)461 ± 524252 ± 3830.004

The waiting time for LT recipients in the MELD era was significantly shorter compared to the pre-MELD era (252 days vs. 461 days).

The MELD scores and waiting time of LT recipients with calculated MELD scores used for patients who received a MELD score exception for HCC is also shown in Table 2. The listing MELD score and MELD score at LT were similar.

Since the MELD score exception prioritizes patients with stage II HCC, we repeated the analysis by removing all patients who had stage II HCC (Table 3). Transplant recipients in the MELD era had a significantly higher MELD score at listing and at LT and a shorter waiting time. The CTP score was also significantly higher.

Table 3. MELD Scores and Waiting Time for Patients Undergoing a First Liver Transplant Since 1995 Excluding Patients With Stage II HCC Who Would Have Been Given a MELD Score Exception
 Pre-MELD era (n = 66)MELD era (n = 88)P value
  1. NOTE: All values are mean ± standard deviation.

Transplant CPT score10.0 ± 1.811.0 ± 1.70.002
Listing MELD score17.1 ± 6.520.0 ± 7.80.01
Transplant MELD score19.8 ± 8.323.3 ± 6.90.006
Waiting time (days)471 ± 542272 ± 3910.01

A comparison of recipients with HCC and those without HCC in the MELD era is shown in Table 4. Almost all the HCC patients had underlying viral hepatitis. The recipient age and race and donor age did not differ between the 2 groups. The HCC patients had significantly lower CTP scores, listing and transplantation MELD scores, but the waiting time was similar.

Table 4. Characteristics of 118 Patients Undergoing a First Liver Transplant Since February 2002 Who Were Given a MELD Exception for HCC Compared to Patients Without HCC
 HCC (n = 30)Non-HCC (n = 88)P value
  1. NOTE: All values mean ± standard deviation.

  2. Abbreviations: NS, not significant; HBV, hepatitis B virus.

Mean recipient age (years)54.2 ± 4.654.3 ± 6.1NS
Race (%)   
 White7783NS
 Black1011NS
 Hispanic136NS
Diagnosis (%)   
 HCV37150.02
 Alcohol7260.04
 HCV/Alcohol3738NS
 HCV/HBV2060.03
 Others0160.02
Mean donor age47.4 ± 16.943.6 ± 17.4NS
Transplant CTP score8.1 ± 1.711.0 ± 1.7<0.0001
Listing MELD score12.3 ± 3.520.0 ± 7.8<0.0001
Transplant MELD score12.8 ± 4.023.3 ± 6.9<0.0001
Waiting time (days)192 ± 358272 ± 391NS

Figure 1 demonstrates the additions and removals from the waiting list from 1995 to 2005. From 2002 onward there appeared to be an increase in the waiting list additions but the number of patients removed from the waiting list that died or who were too sick to receive transplantation did not change. This also occurred after excluding patients who were listed as status 7 at the time of removal.

Figure 1.

The effect of the MELD system on waiting list additions and removals for death or too sick to receive transplantation in the VA Pittsburgh Healthcare System.

Patient and graft survival after LT is shown in Figure 2. There was no significant difference between the MELD and pre-MELD era with 75% 4-yr-survival.

Figure 2.

Kaplan-Meier curves demonstrating patient and graft survival after LT in the pre-MELD and MELD era. (P = 0.25 for patient survival and P = 0.38 for graft survival).

DISCUSSION

The present study demonstrates that the implementation of the MELD score has resulted in a very significant decrease in the waiting time for LT in U.S. veterans from an average of 15 months to 8 months. However, patients are still presenting at a similar stage of advanced liver disease. The listing MELD score was higher in the MELD era recipients but not significantly so. The MELD score of patients receiving transplantation since February 2002 was significantly higher than in previous years although the CTP score at the time of LT did not change. Together these findings indicate that the MELD system has favorably impacted upon LT in U.S. veterans in that sicker patients are receiving transplantation with a shorter waiting time.

Some of the difference in MELD score between the transplant recipients since 2002 was due to the MELD score exception for recipients with HCC. Table 2 demonstrates that if the MELD score exception was replaced by the patient's calculated MELD score, patients received transplantation with a mean MELD score of 20.7, compared to 23.4 using the MELD exception. However, excluding patients with HCC from the analysis demonstrates that patients are being listed with a significantly higher MELD score and undergo transplantation with a higher CTP score and MELD score compared to the pre-MELD era. The waiting time was still significantly shorter in the MELD era. Comparing MELD and CTP scores of recipients with HCC and those without HCC, it is apparent that the former have less advanced liver disease at the time of transplantation. The waiting time was similar reflecting the overall decrease seen under the MELD system.

Some of this decrease in waiting time could also be due to more availability of donor organs. The mean donor age was significantly higher in the MELD era recipients, perhaps indicating a greater willingness to accept older organs that may have been turned down in earlier years, or it may be a reflection of the increase in donor age seen over the last few years.

The impact of the MELD system on waiting list additions and removals was difficult to ascertain. The number of patients added to the list appeared to increase after 2002, particularly more recently in 2004-2005, but similar levels were seen in the mid 1990s. This may have reflected recent staffing issues in the transplant program at the VA in Pittsburgh and lack of alternative transplantation centers for VA patients in earlier years. Removals for death on the waiting list or being too sick to receive transplantation did not appear to change from the pre-MELD to the MELD era.

Examination of the impact of the MELD score on LT throughout the United States suggests that it has improved organ allocation without affecting early transplant survival rates.15 As seen in the present study, several investigators have also demonstrated the dramatic influence of the HCC MELD score exception in increasing the number of patients with HCC undergoing transplantation, with a decrease in the waiting time.16, 17

MELD appears to be effective in prioritizing transplant for sicker patients but it remains to be seen if this influences long-term outcome after transplantation. The present study demonstrates that patient and graft survival were similar in the pre-MELD and MELD eras despite patients in the MELD era being sicker at the time of transplantation (Fig. 2). Although data on LT in the veteran population is limited a recent study comparing LT in veterans and nonveterans suggested a similar survival when recipient age and gender, etiology of liver disease, and MELD score were accounted for.11

Our findings illustrate that veteran patients with cirrhosis often have advanced disease at presentation for transplantation that may be due to later referral. Investigators from a large VA hospital recently examined the referral rate for LT in patients who met the American Association for the Study of Liver Diseases guidelines and found that only 41 of 199 (21%) patients were referred.18 However, most patients for whom transplantation was not considered had potential contraindications that were inferred such as active alcohol use. Contraindications for transplantation may be more important reasons why patients appear to be sent late, although the process for LT listing in the VA may be partially responsible for the perceived delay in patient listing.19 There are currently 4 VA centers in the country offering LT but a potential patient needs to be initially evaluated in their local VA medical center with blood tests, imaging, cardiopulmonary testing, and psychosocial assessment. The completed evaluation is then sent to the central VA office in Washington, DC, and is reviewed by VA transplant physicians. If the patient is thought to be an acceptable candidate, he/she is then sent to 1 of the 4 VA transplant centers for further assessment. This process usually takes several months.

There were some limitations to the findings of this study. The single center analysis of 1 VA LT center may not be generalizable to other VA centers. However, the other 3 VA transplant centers have also shown a similar increase in the number of transplants during the MELD era, from 190 transplants (1997-2001) to 300 transplants (2002-2006), perhaps indicating that sicker veteran patients are indeed receiving transplantation (data from VA Transplant Program, Washington, DC). Our center differs significantly from the other 3 VA programs in the nation in recently being an independent LT program, not affiliated with a university. In the pre-MELD era our center was affiliated with a university. The study was retrospective and included patients receiving transplantation more than 10 yr ago. Part of the reason why so many more patients with HCC received transplantation recently may be better detection techniques and more emphasis on screening because of the MELD exception.

There are regional differences in MELD scores at the time of transplantation and of patients dying on the waiting list. Certain regions have significantly higher MELD scores and waiting times than the national average and are affected by the number of competing transplant centers in the region.20 Our center is in region 2, which has a shorter waiting time than average.21

In conclusion, implementation of the MELD system has led to a significant decrease in waiting time for LT in U.S. veteran patients. The sickest patients are being identified by the MELD score and are undergoing LT with no change in patient or graft survival.

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