Life expectancy without a transplant for status 1A liver transplant candidates

Abstract

Status 1A liver transplant candidates are given the highest medical priority for the allocation of deceased donor livers. OPTN policy requires physicians to certify that a candidate has a life expectancy without a transplant of less than seven days for that candidate to be given status 1A. Additionally, candidates receiving status 1A must have one of six medical conditions listed in policy. Using SRTR data from all prevalent liver transplant candidates from 2010 – 2020, we used a bias-corrected Kaplan—Meier model to calculate the survival of status 1A candidates and to determine their life expectancy without a transplant. We found that status 1A candidates have a life expectancy without a transplant of 24 (95% CI 20 – 46) days – over three times longer than what policy requires for status 1A designation. We repeated the analysis for subgroups of status 1A candidates based on the medical conditions that grant status 1A. We found that none of these subgroups met the life expectancy requirement. Harmonizing OPTN policy with observed data would sustain the integrity of the allocation process.

1. Introduction

Allocation of deceased donor livers is governed primarily by the model for end-stage liver disease (MELD). Candidates with severe liver dysfunction can be given priority ahead of all candidates with MELD scores via 1A status. The Organ Procurement and Transplantation Network (OPTN) outlines two conditions for an adult candidate to be given status 1A in OPTN Policy 9.1.A for adult candidates.

First, at least one of six medical conditions must apply to the candidate:

1. Fulminant liver failure

2. Anhepatic

3. Primary non-function of a transplanted whole liver within seven days of transplant

4. Primary non-function of a transplanted liver segment within seven days of transplant

5. Hepatic artery thrombosis within seven days of transplant

6. Acute decompensated Wilson’s disease

For most of these medical conditions there are objective criteria in OPTN policy for determining whether they apply to a candidate. Second, the candidate must have a life expectancy without a transplant of less than seven days. In contrast to the first condition, there are no objective criteria in OPTN policy for determining whether a candidate actually has a life expectancy without a transplant of less than seven days.

Using Scientific Registry of Transplant Recipients (SRTR) data from all prevalent liver transplant candidates from 2010 – 2020, we used a bias-corrected Kaplan—Meier model to calculate the without-transplant survival of status 1A candidates. We determined the actual life expectancy of status 1A candidates without a transplant and compared it to the policy requirement. We furthermore stratified status 1A candidates according to the aforementioned medical conditions and repeated the analysis to determine if any subgroup of status 1A candidates had a life expectancy without a transplant of less than seven days.

2. Methods

2.1. Data Source

This study used data from the Scientific Registry of Transplant Recipients (SRTR). The SRTR data system includes data on all donor, wait-listed candidates, and transplant recipients in the U.S., submitted by the members of the Organ Procurement and Transplantation Network (OPTN). The Health Resources and Services Administration (HRSA), U.S. Department of Health and Human Services provides oversight to the activities of the OPTN and SRTR contractors. This dataset has previously been described elsewhere (1).

2.2. Study Population

We studied all adult (i.e., at least 18 years old at listing) liver transplant waitlist candidates who were newly listed or who had at least one status update during the study period of 01/01/2010 – 01/01/2020. We excluded any candidates who ever had a MELD exception during the study period. Medical condition for status 1A was determined using the SRTR’s status 1 justification standard analysis file.

2.3. Without-Transplant Survival Analysis

Kaplan—Meier analysis gives a nonparametric estimate of the probability of survival up to any time, given a data set of independent censored survival times. We computed a bias-corrected (2) Kaplan—Meier estimate of the without-transplant survival over time for status 1A candidates. Status 1A candidates are given the highest allocation priority for deceased donor livers and their high probability of transplant introduces bias into the traditional Kaplan—Meier survival estimation. We corrected for this using inverse probability censoring weights, like what was described in Robbins and Finkelstein (2–4).

For each candidate in our cohort who ever had status 1A, we found the first instance that candidate was given status 1A. The time from that observation to an event – either death or censoring – was recorded. Candidates with removal code 8 (“Died”), 5 (“Medically unsuitable”), or 13 (“Candidate condition deteriorated, too sick for transplant”) were counted as death. All other candidates were censored, either by transplant, by the conclusion of the study period, or by removal from the waitlist for any other reason.

2.4. Life Expectancy Without a Transplant

We defined life expectancy without a transplant as the median survival time, i.e., the largest time t such that the probability of surviving until time t without a transplant is at least 50%. We used bootstrapping to get a 95% confidence interval (CI) for the life expectancy without a transplant. In particular, the 95% confidence interval is given by the 2.5^th and 97.5^th percentiles of the bootstrap-based life expectancies.

3. Results

Our cohort contained 3,291 candidates who ever received status 1A. Of those 3,291 candidates, 605 (18.4%) died on the waitlist and 2,051 (62.3%) received a transplant. The bias-corrected Kaplan—Meier survival for status 1A candidates is given in Figure 1 with the 95% confidence interval. The life expectancy of status 1A candidates without a transplant was estimated at approximately 24 days. Using 200 bootstrap iterations, we determined the 95% confidence interval for life expectancy as (20, 46) days.

Figure 1.

Bias-corrected without-transplant survival for status 1A candidates overall with 95% confidence interval. Estimated life expectancy without a transplant was approximately 24 days.

Using the SRTR’s status 1 justification standard analysis file, we determined for each candidate the medical condition which granted status 1A. We could not distinguish between candidates who were given status 1A because of primary non-function of a transplanted whole or segmented liver, or hepatic artery thrombosis (HAT), within seven days of transplant; therefore candidates with these medical conditions were combined into a single status 1A subgroup (“Primary Non-Function or HAT”). Anhepatic state could not be determined based on the status 1 justification file, and for some candidates no data could be found. These candidates were similarly combined into a single status 1A subgroup (“Unknown”).

Table 1 provides a breakdown of candidates in our cohort by status 1A subgroup. The most common medical condition for receiving status 1A was fulminant liver failure (n = 2,332), followed by primary non-function or HAT within seven days of transplant (n = 432), unknown (n = 395), and acute decompensated Wilson’s disease (n = 132). Figure 2 provides the bias-corrected Kaplan-Meier survival for status 1A candidates with fulminant liver failure (Figure 2a), primary non-function or HAT within seven days of transplant (Figure 2b), acute decompensated Wilson’s disease (Figure 2c), and for candidates whose medical condition was unknown (Figure 2d). Life expectancy (95% CI) was estimated as 24 (19, 90) days for candidates with fulminant liver failure, 38 (22, 90) days for candidates with primary non-function or HAT within seven days of transplant, 17 (11, 90) days for candidates with acute decompensated Wilson’s disease, and 27 (15, 39) days for candidates whose medical condition was unknown.

Table 1.

Number of status 1A candidates, transplants, and deaths overall and by medical condition that granted status 1A.

	N	Transplanted (%)	Died (%)
Overall	3,291	2,051 (62.3)	605 (18.4)
Fulminant Liver Failure	2,332	1,453 (62.3)	423 (18.1)
Primary Non-Function or HAT	432	240 (55.6)	88 (20.4)
Wilsons	132	112 (84.8)	13 (9.8)
Unknown	395	246 (62.3)	81 (20.5)

Figure 2.

Bias-corrected without-transplant survival for status 1A candidates with 95% confidence interval by medical condition; (a) fulminant liver failure (life expectancy 24 days), (b) primary non-function or hepatic artery thrombosis within seven days of transplant (life expectancy 38 days), (c) acute decompensated Wilson’s disease (life expectancy 17 days), and (d) unknown (life expectancy 27 days).

4. Discussion

In this national study of the liver transplant waiting list, we found that candidates who were given status 1A had a life expectancy of 24 (95% CI 20 – 46) days without a transplant. This is in contrast to OPTN policy, which stipulates that candidates can be given status 1A only if their life expectancy without a transplant is less than seven days. We furthermore stratified status 1A candidates according to the medical conditions that grant status 1A and repeated our analysis. We found that none of these subgroups had a life expectancy without a transplant of less than seven days. The OPTN policy language, therefore, does not align with the observed life expectancy.

Other researchers have investigated the survival of status 1A candidates. VanDerwerken et al. showed that the without-transplant survival for status 1A candidates was higher than MELD 40 candidates at 3, 7, and 14 days (3). Sharma et al. similarly showed that status 1A candidates have better 14-day without-transplant survival than candidates with a MELD score above 40 (before rounding) (5). To our knowledge, however, no one has investigated whether current practice is aligned with the OPTN’s policy that status 1A candidates have a life expectancy without a transplant of less than seven days.

OPTN policy provides no means for determining whether a candidate (or group of candidates) has a life expectancy without a transplant of less than seven days. This ambiguity forces physicians to use their best judgement when requesting status 1A without any assurance they are complying with OPTN policy. By contrast, OPTN policy does provide objective criteria for determining whether a candidate has one of the six medical conditions required for status 1A. For example, an adult candidate may be granted status 1A if he has primary non-function of a transplanted whole liver within 7 days of transplant, with aspartate aminotransferase greater than or equal to 3,000 U/L and at least one of the following: INR greater than or equal to 2.5; arterial pH less than or equal to 7.30; venous pH less than or equal to 7.25; or lactate greater than or equal to 4 mmol/L. Physicians can show that their candidates meet these criteria with objective laboratory tests. However, OPTN policy provides no objective criteria by which physicians can show that their candidates have a life expectancy without a transplant of less than seven days.

OPTN policy should be harmonized with the observed data to sustain the integrity of the allocation system. An immediate solution would be to remove the life expectancy condition from policy, as there are currently no objective means to determine that it applies to a specific group of candidates. Another option would be to find objective criteria for having a life expectancy without transplant of less than seven days. Safwan et al. have shown that status 1A candidates can be stratified into high- and low-risk groups (6). Although they did not show whether high-risk status 1A candidates met the life expectancy condition, their stratification can be a starting point for determining whether a candidate would meet the life expectancy condition if it were retained.

Status 1A liver transplant candidates are given the highest medical priority for the allocation of deceased donor livers. OPTN policy requires physicians to certify that a candidate has a life expectancy without a transplant of less than seven days for that candidate to be given status 1A. We found that status 1A candidates have a life expectancy without a transplant of 24 (95% CI 20 – 46) days – over three times longer than what policy requires for status 1A designation. Harmonizing OPTN policy with observed data would sustain the integrity of the allocation process.

Table 2.

Life expectancy with 95% confidence interval of status 1A candidates overall and by medical condition that granted status 1A.

	N	Life Expectancy (Days)	95% Confidence Interval
Overall	3,291	24	(20, 46)
Fulminant Liver Failure	2,332	24	(19, 90)
Primary Non-Function or HAT	432	38	(22, 90)
Wilsons	132	17	(11, 90)
Unknown	395	27	(15, 39)

Abbreviations:

MELD

Model for End-Stage Liver Disease

OPTN

Organ Procurement and Transplantation Network

SRTR

Scientific Registry of Transplant Recipients