1 INTRODUCTION

Intestine transplant remains the least common form of solid organ transplant and one of the most challenging. Despite 30 years of clinical experience, long-term outcomes for grafts and patients are considerably lower than those for other major organ transplants, with the possible exception of lung transplant, but intestine transplant has been demonstrated to be lifesaving and to improve quality of life for very many patients. The number of intestines transplanted per year peaked in 2007 and has declined since then. Initially this was most marked for pediatric populations with intestinal failure, because of improved intestinal rehabilitation; however, over the past few years, pediatric intestine transplant rates have plateaued. For the past decade, numbers of intestine transplants for adults have exceeded those for children, but adult intestine transplant rates have been falling, and this is most notable for those in need of combined intestine-liver transplant. A potential reason for this decrease may be due to changes in liver allocation policy and the 10% model for end-stage liver disease (MELD) increase afforded to adult patients requiring combined intestine-liver transplant, an increase which may no longer provide these patients sufficient priority.

There is much discussion regarding excessive nonuse rates for other organs, but for intestine there were 97 intestines procured for transplant in 2021 and 96 transplants carried out. It will be important to continue to monitor this trend, as more organ offers are needed to serve these candidates who often have very long waiting times once placed on the waitlist.

Another concern is how the COVID-19 pandemic may have influenced intestine transplant activity. With the small increases in waitlist additions, overall intestine transplant rates, and overall intestine transplants undertaken in 2020 and 2021 compared with those done in 2019, and no change in pretransplant mortality rates, it may be fair, albeit on the basis of limited nongranular data, to suggest that the overall effect of COVID-19 on intestine transplant activity in the United States has been negligible.

If we look at equity in intestine waiting lists and transplant numbers, understanding that these limited data do not tell the full story, there are no glaring differences in waitlist and transplant proportions based on race and ethnicity compared with the overall US population. Information on the waiting list, transplants, and outcomes is presented for intestine transplants either alone or in combination with liver. Both types include multivisceral transplants distinguished by inclusion or exclusion of liver.

2 WAITING LIST

Waitlist additions were similar in total to the previous year (144 in 2020 and 143 in 2021), although with 239 waitlist additions in 2010, the trend over 12 years is clearly toward fewer listings (Figure IN 1). This trend is also reflected in the number of prevalent patients awaiting intestine transplant: 466 candidates in 2010 (225 for intestine alone and 241 for combined intestine and liver) compared with 364 candidates waiting in 2021 (180 and 184 for isolated intestine and combined intestine and liver, respectively) (Figure IN 2). Over the preceding decade, there has been a gradual increase in the number of adults waiting for intestine transplant compared with candidates younger than 18 years, and in 2021 the adult numbers surpassed those of pediatric candidates for the first time ever with 56% of the waiting list aged 18 years or older (Figure IN 3). The racial and ethnic mix of the waiting list has been relatively consistent since 2010, with White patients making up between 59% and 64% of the list; Black patients, 15% to 21%; Hispanic patients, 14% to 18%; and Asian patients, 2% to 4% (Figure IN 5). Purely for reference, the US population in 2020 was 59.7% White, 12.6% Black, 18.6% Hispanic, and 5.9% Asian.¹ The most common etiology of intestinal failure on the waiting list remained short-gut syndrome (SGS; 47%), which encompasses both congenital and noncongenital SGS, as well as necrotizing enterocolitis and probably a significant number in the other/unknown group (Figure IN 6). Enteropathies and intestinal pseudo-obstruction syndromes are rare and account for only about 10% of all indications for listing for intestine transplant (Figure IN 6).

Table IN 1 shows the demographic characteristics of intestine transplant candidates by whether they are simultaneously awaiting a liver transplant. Generally, these characteristics are similar between the two cohorts, although it appears that listing for combined intestine and liver is more common in male candidates and older patients. Candidates, in the main, come from metropolitan areas either close to the transplant center or from distances greater than 150 miles, presumably other metropolitan centers without an intestine transplant program. Medical characteristics of the two groups are shown in Table IN 2, and other than individuals with chronic intestinal pseudo-obstruction who were more likely to be listed for isolated intestine, other diagnostic groups were equally likely to be listed for isolated intestine and combined intestine-liver transplant. Major ABO blood groups were equally represented between intestine alone and combined intestine and liver, and approximately in line with the average distribution of blood groups in the US population.

The proportion of candidates with waiting times fewer than 90 days has increased in the past 2 years but remains lower than in 2010 (20.3% waiting fewer than 90 days in 2021 compared with 31.1% in 2010), and the trend for those waiting more than 2 years appears to be toward greater numbers (36.5% waiting more than 2 years in 2021 compared with 27.5% in 2010) (Figure IN 7). Transplant rates have risen over the past 2 years from the nadir in 2019 of 34.8 transplants per 100 patient-years to 44.9 transplants per 100 patient-years in 2021, suggesting that maybe the COVID-19 restrictions did not prevent intestine transplants from happening; but, again, this rate is lower than that seen in 2010 of 60.3 transplants per 100 patient-years (Figure IN 9). Transplant rates for children and adolescents have been fairly stable during the 12-year period (range, 20-35 transplants per 100 patient-years), whereas those for adults have varied widely from year to year (range, 60-130 transplants per 100 patient-years) (Figure IN 10). Transplant rates are not clearly different by race and ethnicity (Figure IN 11), nor among candidates awaiting either isolated intestine or combined intestine-liver transplant (Figure IN 12).

In 2021, 88 candidates were removed from the isolated intestine waiting list: 57 (64.8%) underwent deceased donor transplant, 3 (3.4%) died, 16 (18.2%) were removed from the list because their condition improved, and 11 (12.5%) were removed for other, unspecified reasons (Table IN 5). Outcomes at 3 years for newly listed candidates for isolated intestine transplant in 2016 through 2018 show that 67.4% underwent deceased donor transplant, 3.8% died, 14.2% were removed from the list, and 14.6% were still waiting 3 years after listing (Figure IN 13). Likewise, 75 candidates were removed from the intestine-liver waiting list in 2021: 38 (50.7%) underwent deceased donor transplant, 12 (16.0%) died, 7 (9.3%) were removed from the list because their condition improved, and 10 (13.3%) were considered too sick to undergo transplant (Table IN 5). Of intestine-liver candidates listed from 2016 through 2018, 67.8% underwent deceased donor transplant within 3 years, 11.4% were removed from the list, 10.2% died, and 10.6% were still waiting (Figure IN 14).

The overall pretransplant mortality for intestinal transplant candidates has ranged from 6 to 12 deaths per 100 patient-years since 2010 (Figure IN 15), and rates vary by age. Pretransplant mortality is higher for adult candidates, ranging from 9.6 deaths per 100 patient-years in 2017 to 24.5 deaths per 100 patient-years in 2014. For pediatric candidates, the range was from a low of 2.0 deaths per 100 patient-years in 2020 up to 5.4 deaths per 100 patient-years in 2012 (Figure IN 16). Noticeably, there was no increase in pretransplant mortality seen with the appearance of COVID-19. Pretransplant mortality in 2021 was, as has always been seen previously, higher for combined intestine-liver (14.1 deaths per 100 patient-years) than for isolated intestine transplant candidates (2.8 deaths per 100 patient-years) (Figure IN 19).

3 DONATION

In 2021, 97 intestines were recovered from deceased donors (Figure IN 21). The greatest proportion of intestine donors in 2021 were aged younger than 18 years (56.7%) (Figure IN 23). Most intestine donors were White (60.8%) (Figure IN 25). The overall rate of intestines recovered for transplant and not transplanted was only 1% in 2021 (Figure IN 26). The most common cause of death among deceased intestine donors has historically always been head trauma, and this was again the case in 2021 with 56.7% of deceased intestine donors being as the result of head injury, although in 2020 there was a clear increase in the proportion of donors who died of anoxia (Figure IN 28).

4 TRANSPLANT

The lowest number of intestine transplants done in any 1 year since 2010 was 81 in 2019 (Figure IN 29). An increase in transplant activity has been seen in the past 2 years, with 91 intestine transplants performed in 2020 and 96 in 2021. Of the 96 transplants done in the past year, 58 were intestine alone and 38 were liver-inclusive transplants (Figure IN 30).

Pediatric recipients of intestine transplants outnumbered adult recipients for at least the first 20 years of intestine transplantation, but since the late 2000s the number of intestine transplant recipients older than 18 years has overtaken that of recipients who are children or adolescents. Pediatric recipient counts declined from 62 in 2010 to a low of 32 in 2019, with only a slight rebound to 36 in 2021; adult recipient counts fell from 89 in 2010 to 60 in 2021 (Figure IN 31). In 2021, a little more than half of intestine-liver recipients were aged younger than 18 years (55.3% vs 25.9% of intestine-alone recipients) (Table IN 6). Most recipients had private insurance and resided in metropolitan areas (Table IN 6). Short-gut syndrome was the main cause of disease leading to both intestine and intestine-liver transplant (Table IN 7).

Most recipients of an intestine-containing allograft in 2021 waited less than a year from listing to their transplant: 75.8% of isolated intestine recipients and 65.8% of intestine-liver recipients (Table IN 8).

5 IMMUNOSUPPRESSION

The use of induction immunosuppression with antithymocyte globulin or interleukin 2 receptor blocking antibody is common in intestine transplant and was used in almost 80% of cases in 2021 (Figure IN 35). Tacrolimus remains the mainstay for maintenance immunosuppression, used mainly in combination with corticosteroids or mycophenolate mofetil or both (Figure IN 36). There also appears to be a decrease in the use of steroid-free regimens, although Figure IN 36 only specifies the combination of tacrolimus and mycophenolate agents without steroids, which was used in almost 30% of cases in 2012 and less than 10% in 2021.

6 OUTCOMES

There has been no noticeable change in graft survival at any time point after intestine transplant (with or without liver) across the period from 2010 through 2021 (Figure IN 37 and Figure IN 38). Graft survival at 5 years for the cohort who underwent transplant in the period 2014 through 2016 is better for those who underwent transplant at a younger age, with recipients younger than 18 years having a 62% graft survival at 5 years compared with adults having 43% survival (Figure IN 39). Graft survival for this same cohort based on whether the allograft contained the liver is essentially similar (Figure IN 40), as is the outcome for residence in a metropolitan versus non-metropolitan area (Figure IN 41).

Patient survival for the 2014-2016 cohort based on whether a patient received the liver along with the intestine shows better survival short term for intestine-alone recipients (1-year patient survival 86.4% for isolated intestine recipients vs 75.2% for recipients of combined intestine and liver), but this difference narrowed considerably by 5 years (61.2% vs 58.1%, respectively) (Figure IN 46).