1 Introduction

In this 2022 Annual Data Report, pediatric data have been separated from adult data to a greater extent than in previous years; but unlike chapters for other specific organs, there has not been a need for a completely separate pediatric section.

As has been the trend for more than a decade now, the overall activity in intestine transplantation has been in decline; waitlist additions, prevalent candidates on the waiting list, total number of intestine donors, and the overall number of intestine transplants all appear to have been decreasing. There were some noticeable dips in numbers in 2019, but the subsequent 3 years of data have not altered the overall trends. Again, as seen in previous Annual Data Reports, the decreasing numbers of candidates for and recipients of an intestine allograft are most marked in the pediatric populations, largely due to the well documented advances in medical and nontransplant surgical care for intestinal failure. Adults now account for 61% of the prevalent waiting list, where once pediatric candidates heavily outweighed the number of adults listed.

Despite a reduced demand for intestine transplant, there has not been a proportional reduction in waitlist deaths or removals due to being “too sick for transplant” among waitlist candidates, especially for the sicker patients listed for combined intestine-liver. There were 32 transplants of this type in 2022, but 16 candidates either died or were removed from the waiting list due to being “too sick for transplant.” Transplant rates have decreased, particularly for adults in need of a liver-inclusive graft, since the most recent changes to the liver allocation policy. A proposal to increase the priority for allocation has been approved by the OPTN Board of Directors and implemented, and it is hoped that this change will improve transplant rates for these candidates in the future.

In terms of posttransplant outcomes, there may be a gradual trend toward reduced graft failure rates in those receiving an intestine without liver, but this trend was not seen among recipients of intestine-with-liver allografts. Patient survival remains better for pediatric recipients and for those receiving an isolated intestine transplant.

The incidence of posttransplant lymphoproliferative disorder (PTLD) is higher for those who received a graft without a liver, especially for those recipients who were Epstein-Barr virus (EBV) negative at transplant. The reason for this increased incidence is unclear but may relate to the need for greater immunosuppression in recipients of isolated intestine transplant, as the risk of rejection is thought to be higher.

In this chapter, information on the waiting list, transplants, and outcomes in the United States 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

The total number of new candidates awaiting an intestine-containing allograft in 2022 was 146, which is similar to the number of additions in 2020 and 2021 and higher than the 103 additions in 2019; the peak in the past decade was 211 additions in 2014. The number of candidates listed for intestine alone exceeded that for combined intestine-liver for the first time since 2011 (78 and 68 candidates, respectively) (Figure IN 1). The number of prevalent patients awaiting intestine transplant continues to decrease, with 167 awaiting intestine alone and 180 candidates awaiting intestine with liver (Figure IN 2). The distribution of adult candidates listed in 2021 surpassed, for the first time, that of pediatric candidates, and the trend has continued in 2022 with 61% of the waiting list being candidates aged 18 years or older; this is a complete reversal from a decade ago when 60% of the waiting list were pediatric candidates (Figure IN 3). In terms of the sex distribution of candidates, there has always been a slight predominance of males, which, over the 12-year period of 2011 through 2022, averages 52.6% male and 47.4% female candidates (Figure IN 4). The racial and ethnic mix of the waiting list has been relatively consistent over the past decade (2013-2022), with White patients making up between 57.3% and 61.5% of the list; Black patients, 17.5% to 21.4%; Hispanic patients, 14.6% to 18.7%; and Asian patients, 2.5% to 4.4% (Figure IN 5). The most common etiology of intestinal failure on the waiting list remained short-gut syndrome, which encompasses both congenital and noncongenital forms of the syndrome, as well as necrotizing enterocolitis and probably a significant number in the Other/unknown group (Figure IN 6). However, it is notable that there has been a decrease in the proportion of congenital causes of short-gut syndrome and necrotizing enterocolitis, both pediatric diagnoses, although interpretation is somewhat obscured by the more than 30% of candidates in the Other/unknown category. Enteropathies and intestinal pseudo-obstruction syndromes are rare and collectively continue to 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 demographics are similar between the two cohorts, although it appears that listing for combined intestine-liver is more common in candidates who are male and/or White. Candidates tend to come from metropolitan areas close to the transplant center or from distances of 150 miles or greater, presumably from other metropolitan centers without an intestine transplant program. Medical characteristics of the two groups are shown in Table IN 2. Individuals with chronic intestinal pseudo-obstruction are proportionately more likely to be listed for isolated intestine, while pediatric candidates with a history of necrotizing enterocolitis are twice as likely to need a combined intestine-liver transplant. 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-liver, and approximately in line with the distribution of blood groups in the US population.

The proportion of candidates with waiting times on the intestine transplant list of less than 90 days has remained stable in the past 3 years at around 20%. The proportion waiting less than 90 days decreased in 2019 and was accompanied by a peak in those waiting over 2 years (Figure IN 7). The significant number of candidates for intestine transplant who are on the waiting list for more than 2 years is also shown in Table IN 3. The distributions of adult and pediatric candidates listed for either intestine-alone or intestine-liver transplant both cluster around 50% (Figure IN 8 and Figure IN 9). Most candidates for intestine-alone or combined intestine-liver transplant are awaiting their first transplant, but of those awaiting retransplant, a greater number are listed for a liver-containing allograft (Table IN 3).

Figure IN 10 shows that overall transplant rates for adults have decreased over the past 7 years from 114.8 transplants per 100 patient-years of waiting time in 2016 to 55.6 transplants per 100 patient-years in 2022. Pediatric transplant rates have fluctuated between 20.3-34.9 transplants per 100 patient-years over the past 12 years (Figure IN 11), with the overall pediatric transplant rate in 2022 being 22.8 transplants per 100 patient-years. When looking at transplant rates by age group in adults, the most noticeable decrease in transplant rates occurred among those aged 18-34 and 35-49 years (Figure IN 12). In children and adolescents, transplant rates have remained relatively stable (Figure IN 13), although for all age groups, both adults and pediatric, the total numbers are very small so year-to-year variability in transplant rates tends to fluctuate. The extent of this fluctuation is also evident in transplant rates by race and ethnicity. On average over the past 12 years, transplant rates for White candidates have tended to be higher than those for other groups (51.2 transplants per 100 patient-years for White candidates compared with 33.8, 34.2, and 39.2 transplants per 100 patient-years for Asian, Hispanic, and Black candidates, respectively), but beyond this no other trends are apparent (Figure IN 14). The transplant rate for candidates awaiting intestine alone is currently higher than that for those in need of a liver-containing allograft; the latter decreased from 45.5 transplants per 100 patient-years in 2011 to 27.6 transplants per 100 patient-years in 2022 (Figure IN 15).

In 2022, 71 candidates were removed from the isolated intestine waiting list (Table IN 4): of these, 49 (69.0%) underwent deceased donor transplant, 8 (11.3%) died or were too sick for transplant, 7 (9.9%) were removed from the list because their condition improved, 6 (8.5%) were removed for other, unspecified reasons, and 1 (1.4%) refused transplant (Table IN 5). Outcomes at 3 years for newly listed candidates for isolated intestine transplant in 2017 through 2019 show that 67.7% underwent deceased donor transplant, 4.3% died, 14.5% were removed from the list, and 13.4% were still waiting 3 years after listing (Figure IN 16). Likewise, 61 candidates were removed from the intestine-liver waiting list in 2022; of these, 33 (54.1%) underwent deceased donor transplant, 16 (26.2%) died or were too sick for transplant, 4 (6.6%) were removed from the list because their condition improved, 6 (9.8%) were removed for other, unspecified reasons, and 2 (3.3%) refused transplant (Table IN 5). Of intestine-liver candidates listed from 2017 through 2019, 65.0% underwent deceased donor transplant within 3 years, 10.6% were removed from the list for reasons other than death or transplant, 11.1% died, and 13.4% were still waiting after 3 years on the waiting list (Figure IN 17).

Pretransplant mortality rates for intestine transplant candidates by race and ethnicity average less than 8.0 deaths per 100 patient-years for all groups from 2011 to 2022, although with considerable variation from year to year (Figure IN 18). Again, pretransplant mortality rates for male and female candidates also average less than 8.4 deaths per 100 patient-years, but there appears to be a trend toward fewer deaths in female candidates, with rates in 2011 at 15.7 deaths per 100 patient-years decreasing to 4.9 deaths per 100 patient-years in 2022 (Figure IN 19). The pretransplant mortality rate in 2022 for candidates listed for intestine with liver (10.4 deaths per 100 patient-years), as has always been the case, exceeds that of those awaiting intestine-alone transplant (5.4 deaths per 100 patient-years) (Figure IN 20). When broken out by adult or pediatric candidates, the adults have higher pretransplant mortality rates for both intestine alone and intestine with liver (Figure IN 21 and Figure IN 22). Noticeably, pediatric pretransplant mortality rates for those listed for a liver-inclusive graft have decreased quite dramatically over the past few years (Figure IN 22).

3 Donation

The year 2022 saw only 87 intestines recovered for transplant, only one more than the lowest number per year in 2019 (Figure IN 23). The greatest proportion of intestine donors in 2022 were younger than 18 years, but this age group also showed the greatest decline in absolute number of intestines recovered (Figure IN 24) and a modest decline in the proportion of intestines recovered compared with other age groups (Figure IN 25). A little over 60% of intestine donors were male (Figure IN 26) and also just over 60% were White (Figure IN 27). The overall rate of intestines recovered for transplant and not transplanted was 4.6% in 2022 (Figure IN 28). The most common cause of death among deceased intestine donors has historically always been head trauma, and this was again the case in 2022 with 50.6% of deceased intestine donors dying as a result of head injury (Figure IN 30).

4 Transplant

In 2022, a total of 82 intestine-containing transplants were carried out across the United States; this was only one more than in 2019, which saw the lowest number of intestine transplants done in any one year in the past 12 years (Figure IN 31). Of these, 60 intestines were transplanted into an adult recipient (41 isolated intestines and 19 intestine-liver) (Figure IN 32) and only 22 in children and adolescents (9 isolated and 13 intestine-liver) (Figure IN 33). There were fairly similar numbers of female and male recipients over the past decade; in 2022, there were 39 and 43 transplants, respectively (Figure IN 34). Overall, the numbers of intestine transplants have proportionately decreased for Black, Hispanic, and White candidates since 2011; the numbers for other racial and ethnic groups are too small to draw any conclusions (Figure IN 35).

Table IN 6 shows the demographic characteristics of intestine transplant recipients; approximately 40% of intestine-liver recipients, but only 18% of intestine-without-liver recipients, were of pediatric age. About 45% of intestine transplants were paid for by private insurance and about 35% by Medicaid, with most of the remaining cases supported by Medicare (15%) (Table IN 6). Most recipients lived in metropolitan areas (Table IN 6). Short-gut syndrome remains the main cause of disease leading to both intestine and intestine-liver transplant (Table IN 7).

Most recipients of an intestine-containing allograft in 2022 waited less than a year from listing to their transplant: 80% of recipients of isolated intestine and 72% of recipients of intestine-liver (Table IN 8). Less than 10% of recipients had had a previous intestine transplant, and, of these, two received an isolated intestine and five received an intestine-liver allograft (Table IN 8).

5 Immunosuppression

The use of induction immunosuppression with a lymphocyte-depleting agent or interleukin-2 receptor blocking antibody is common in intestine transplant and was used in over 80% of cases in 2022 (Figure IN 37). Tacrolimus remains the mainstay for maintenance immunosuppression, used mainly in combination with corticosteroids or mycophenolate mofetil or both (Figure IN 38).

6 Outcomes

Graft failure rates for intestine without liver have slightly improved over the past 12 years, and the 3- and 5-year graft failure rates for the latest cohorts are the best seen during this 2011-2022 period at 26.7% and 42.4%, respectively (Figure IN 39). These improvements, however, are not seen in the graft failure rates for liver-containing allografts, with 6- and 12-month graft failure rates at over 50%. There also appears to be a worsening trend in 3-year graft failure rates for intestine-liver grafts up until 2019 and no noticeable improvement since 2011 in 5-year graft survival (Figure IN 40). For adults who received an intestine transplant during 2015 through 2017, intestine allograft survival is clearly better for intestine without liver at 1-year posttransplant (82.1% versus 62.2%, respectively), but this advantage is all but lost by 5-year post-transplant (47.6% versus 42.2%) (Figure IN 41). From 2015 through 2017, graft survival for pediatric recipients is overall better than that for adult recipients, and the difference between graft survival for intestine with or without liver favors the liver-containing allografts (1-year survival: 71.9% intestine alone and 79% with liver; 5-year graft survival: 52.6% and 61%, respectively) (Figure IN 42).

The incidence of acute rejection by 1-year posttransplant varies from year to year and is generally in the range of 21.7%-50% for both adult and pediatric intestine transplant recipients, although on average a slightly higher incidence is seen in the pediatric population (Figure IN 44). There is no clear benefit of any of the induction immunosuppressive regimens on the incidence of acute rejection within the first year after transplant (Figure IN 45). The incidence of PTLD is higher in recipients of an intestine without liver (up to 10% in those with negative EBV serology prior to transplant) than in recipients of intestine-liver transplant. Also of note is that the incidence of PTLD in the intestine-liver group of recipients does not seem to be different based on pretransplant EBV serology, with incidence of PTLD of less than 4% in both the negative and positive serology groups (Figure IN 46 and Figure IN 47).

For intestine transplants received during 2015-2017, patient survival after transplant is also better for pediatric populations than for adults. This observation is clearest at 5 years, when patient survival for those who underwent transplant as children and adolescents is 77.2% if they received an intestine alone and 66.7% if intestine-liver, whereas for adult recipients the survival percentages are 61.3% and 46.7%, respectively (Figure IN 48 and Figure IN 49).