1 Introduction

The intestine remains an infrequently transplanted organ. Despite the significant decrease in the number of intestine transplants over the past 2 decades, more recently the number of annual intestine transplants has plateaued over the past 5 years. This has been accompanied by a rise in the use of intestine transplant in adults, with a sustained shift to a greater proportion of transplants being performed in adults rather than children. However, a substantial proportion of intestine-with-liver transplants continue to be required in pediatric patients. The overall decrease in intestine transplant has been largely attributed to the advancement of multidisciplinary intestinal rehabilitation teams, but the persistent need for intestine-with-liver transplants in pediatrics is concerning. In the coming years, recent changes to the priority given to candidates for intestine-with-liver transplant may lead to more frequent combined transplant in adult patients in need.

While the need for intestine transplant may be reduced overall, the burden of disease for those requiring intestine transplant remained high in 2023. This is best evidenced by a total of 18 patients being removed from the waiting list for death or being too sick for transplant, up from 16 in the previous year. Thus, there continues to be a need to improve access to intestine transplant for the most vulnerable patients.

Although early posttransplant graft and patient survival remained higher in those receiving intestine-without-liver transplants, long-term survival continued to be supported by liver inclusion, with nearly identical 5-year graft survival values despite worse early posttransplant graft survival in these recipients. This trend was particularly striking in pediatrics, where both 1- and 5-year graft survival were greater in those also receiving a liver. Despite this, patient survival continued to be lower in recipients of intestine with liver, outlining the complexity involved in the care of these patients. These trends may also highlight the notable heterogeneity in diagnosis requiring transplant, including the striking number of recipients with an underlying diagnosis of venous or mesenteric thrombosis or abdominal tumors in 2023.

The demographic distributions of recipients in 2023 seem to mirror those of the national population. However, donor characteristics reflect a greater-than-expected number of Black donors, out of proportion to the population. Further data will be required to see whether this trend continues. Once again, high rates of posttransplant lymphoproliferative disorder (PTLD) were seen in this population, especially in those who received intestine-without-liver transplant. The lower rate of PTLD in liver-inclusive transplants warrants further exploration.

In this chapter, information on the waiting list, transplants, and outcomes in the United States is presented for intestine-without-liver transplants and combined intestine-liver transplants. Data for both types include multivisceral transplants distinguished by inclusion or exclusion of liver. Of note, this report contains data spanning the duration of the COVID-19 pandemic, with few effects seen on intestine trends over time.

2 Waiting List

Waitlist additions decreased slightly to a total of 135 new additions in 2023 (down from 146 in 2022 and 143 in 2021). For the second consecutive year, intestine-without-liver listing exceeded liver-inclusive listing, with 73 new additions to the intestine-without-liver waiting list (Figure IN 1). The total number of intestine candidates listed at any time during the year remained steady, with 167 listed for without liver and 182 listed for with liver (Figure IN 2). Over 60.0% of those waiting for intestine transplant overall were aged 18 years or older, continuing the trend of more adult candidates since 2021 (Figure IN 3). In terms of sex distribution, 48.1% of candidates were female (Figure IN 4). The racial and ethnic distribution of candidates has not changed much over time; note a new classification of “unreported” has been added to the figure (Figure IN 5). In 2023, candidates were 57.9% White, 18.1% Black, 17.8% Hispanic, 4.9% Asian, and less than 1.0% each of Multiracial, Native American, and unreported. Short-gut syndrome (SGS) remained the most common diagnosis, encompassing necrotizing enterocolitis (8.0%), congenital SGS (13.2%), and noncongenital SGS (Figure IN 6). The 79 candidates listed as “Other/unknown” included write-in diagnoses of 10 individuals with Hirschsprung disease, 27 with portal venous/mesenteric thrombosis, 11 with tumors, 8 with other forms of SGS, and 15 with a primary dysmotility disorder (Table IN 2). Candidates most commonly waited over 2 years prior to transplant, on both the intestine-without-liver and intestine-with-liver lists (Figure IN 7). Whereas the proportion of candidates waiting the longest for combined intestine-with-liver transplant remained at approximately 39.6% (Figure IN 8), the proportion of candidates waiting 2 years or longer for intestine-without-liver transplant has fallen from a peak of over 50.0% in 2019 year by year to the lowest level of 27.5% in 2023 (Figure IN 7). For candidates who remained on the list at the end of 2023, 39.6% of those awaiting intestine without liver and 46.1% of those awaiting intestine with liver had waited more than 2 years for transplant (Table IN 3).

Candidates for intestine transplant without and with liver were similar in terms of age and race and ethnicity (Table IN 1). There was a slight male predominance in those awaiting intestine-with-liver transplant. More than 85.0% of candidates on both waiting lists came from metropolitan areas, which reflects the distribution of population across the United States. Candidates frequently lived 250 miles or more from the transplant center in which they were listed, including 34.4% and 25.2% of those awaiting intestine transplant without and with liver, respectively. Distribution of diagnoses and blood types were similar between those on both waiting lists (Table IN 2). Less than 20.0% of candidates awaiting intestine transplant, both without and with liver, had had a previous transplant (Table IN 3).

Among adult candidates, there have been approximately equal numbers awaiting intestine transplant without or with liver across the past decade, with slightly more (54.5%) requiring intestine without liver in 2023 (Figure IN 9). Among pediatric candidates, over 60.0% of candidates in 2023 required intestine with liver, a percentage that has continued to increase since 2019 (Figure IN 10).

Rates of intestine transplant have remained relatively stable over time, considering the fluctuations expected with such a small number of transplants occurring each year. In 2023, adult candidates on the waiting list underwent transplant at a rate of 53.2 transplants per 100 patient-years (Figure IN 11) and pediatric candidates underwent transplant at a rate of 36.8 transplants per 100 patient-years (Figure IN 12). When examining these transplant rates by candidate age, similar variation from year to year can be observed. However, the transplant rate for individuals aged 65 years and older on the waiting list had consistently been greater than that for other adult age groups from 2019 to 2022, but in 2023 the highest rate was in those aged 50-64 years (Figure IN 13). A similar pattern is seen for pediatric candidates; those younger than 1 year had the highest transplant rate from 2016 to 2022, but in 2023 the highest rate was in those aged 1-5 years (Figure IN 14). Transplant rates have fluctuated by race and ethnicity, although Hispanic candidates seem to have consistently undergone transplant at lower rates since 2016 compared with their non-Hispanic White counterparts (Figure IN 15). Since 2021, candidates with liver colisting have undergone transplant at lower rates, ranging from 27.2-33.2 transplants per 100 patient-years compared with 57.2-60.3 transplants per 100 patient-years in those without liver colisting (Figure IN 16).

There were 138 candidates removed from the waiting list during 2023 (Table IN 4). While 95 of these removals were for deceased donor transplants, 8 candidates on the intestine-with-liver list died while awaiting transplant. An additional 10 candidates, 6 of whom were on the intestine-with-liver list, were removed for being too sick to receive a transplant (Table IN 5).

Three-year outcomes for those who were listed in 2018-2020 for intestine without liver show that 69.6% received a transplant, 4.1% died, 14.6% were removed from the waiting list for other reasons, and 11.7% remained on the waiting list (Figure IN 17). Over that same timeframe, for those listed for intestine with liver, 62.8% received a transplant, 10.2% died, 14.0% were removed from the waiting list for other reasons, and 13.0% remained on the waiting list (Figure IN 18). Mortality rates for candidates on the waiting list have shown large fluctuations by race and ethnicity given the small number of events from year to year (Figure IN 19). Mortality rates seem similar between male and female candidates, again with the caveat of small numbers (Figure IN 20). Those listed for intestine with liver have higher pretransplant mortality, with the 2023 mortality rate being 8.2 deaths per 100 patient-years; the mortality rate for those listed for intestine without liver dropped to 1.0 death per 100 patient-years (Figure IN 21). In adult intestine candidates in 2023, the mortality rates were 1.7 and 8.5 deaths per 100 patient-years for those without and with liver colisting, respectively (Figure IN 22). Pediatric candidates had a similar higher mortality rate for those with liver colisting, at 8.0 deaths per 100 patient-years. There were no pediatric deaths among candidates awaiting intestine transplant without liver in 2023 (Figure IN 23).

3 Donation

The overall number of intestines recovered from deceased donors increased slightly from 87 in 2022 to 99 in 2023 (Figure IN 24). By age, 55 intestine donors (55.6%) in 2023 were younger than 18 years (Figure IN 25 and Figure IN 26), a consistent pattern since 2012, which is reflective of the relatively greater proportion of pediatric candidates in intestine compared with other organs. For example, as shown in the Liver chapter in the previous report, only 6.8% of liver donors in 2022 were younger than 18 years. The percentage of female donors has been trending down since 2020, hitting a nadir of 26.3% of all intestine donors in 2023 (Figure IN 27). The distribution of donors by race and ethnicity in 2023 included 55.6% White, 28.3% Black, 14.1% Hispanic, and 1.0% Asian (Figure IN 28). It is notable that Black individuals made up 18.1% of candidates (Figure IN 5) but 28.3% of donors. The percent of intestines recovered for transplant and not transplanted has remained below 6.0% since 2016 (Figure IN 29). This rate was 4.0% in 2023, down from 4.6% in 2022. A greater percentage of female donors, 7.7%, compared with male donors, 2.7%, had intestines recovered but not transplanted in 2023 (Figure IN 30). Head trauma remained the most common cause of death in intestine donors, accounting for 49.5% in 2023 (Figure IN 31).

4 Transplant

From the 99 intestines recovered for transplant, 95 intestine transplants were performed in 2023, an increase from the 82 performed in 2022 (Figure IN 32). Of the 62 adult intestine transplants in 2023, 16 included a liver, a proportion that continued to decrease over the past few years (Figure IN 33). Of the 33 pediatric intestine transplants, 18 included a liver (Figure IN 34). Of the 95 recipients of intestine transplants, 46 were female (Figure IN 35). The recipient racial and ethnic distribution was as follows: 58.9% White, 17.9% Black, 14.7% Hispanic, 7.4% Asian, and 1.1% Native American (Figure IN 36). This is, again, notable for Black individuals making up 17.9% of recipients but 28.3% of donors in 2023.

In Table IN 6, the demographic characteristics of recipients of intestine without liver are compared with those of recipients of intestine with liver in 2023. The pediatric age range accounted for 24.6% of intestine-without-liver transplants, but a much greater percentage of intestine-with-liver transplants occurred in this age group (52.9%). This is similarly reflected in the higher proportion of recipients with Medicaid insurance among those who received an intestine-with-liver transplant.

The underlying diagnosis of those receiving intestine transplants in 2023 included 46 with noncongenital SGS, 5 with necrotizing enterocolitis, 7 with congenital SGS, and 9 with pseudo-obstruction (Figure IN 37). Most of those with noncongenital SGS (38 recipients) received an intestine-without-liver transplant (Table IN 7). The 28 recipients listed as “Other/unknown” diagnosis included 4 individuals with Hirschsprung disease, 5 with thrombosis, 4 with tumors, 2 with polyposis syndromes, 2 with congenital enteropathy, 6 with a primary dysmotility disorder, and 1 with hepatitis C; for the remainder, no diagnosis was assigned (Table IN 7).

Table IN 8 shows transplant characteristics of those who received an intestine without liver versus with liver in 2023. Most recipients of intestine-without-liver transplant had waited less than 1 year (78.7%), and 20.6% of recipients of intestine-with-liver transplant waited 2 or more years. In a new figure this year, candidates who had received a previous transplant were examined. Eight (8.4%) recipients had received a previous transplant in 2023, a percentage that continued to decrease since a peak of 18.3% of transplants performed in 2017 (Figure IN 38).

5 Immunosuppression

Use of induction agents has increased over time, reaching a new peak in 2023 at 87.4% of all intestine transplants (Figure IN 39). For maintenance immunosuppression, tacrolimus remained the preferred agent, although in 2023 more recipients were placed on a regimen including tacrolimus, steroids, and a mycophenolate agent compared with tacrolimus and steroids alone. The greatest proportion of recipients reported an alternate maintenance immunosuppression plan (Figure IN 40).

6 Outcomes

Graft failure among intestine transplant recipients has remained stable over time. In the most recent cohorts, the graft failure rate for recipients of intestine without liver was 12.2% at 6 months, 14.6% at 1 year, 32.4% at 3 years, 55.3% at 5 years, and 70.7% at 10 years (Figure IN 41). The graft failure rate for recipients of intestine with liver was 36.8% at 6 months, 47.4% at 1 year, 45.0% at 3 years, 58.6% at 5 years, and 65.6% at 10 years (Figure IN 42). This reflects the theorized immunoprotective support that the liver provides to long-term graft function, despite high rates of early graft failure likely due to a more fragile clinical condition at the time of transplant. Specifically examining adult transplants in 2016-2018, those receiving an intestine without liver had graft survival of 78.3% at 1 year and 46.5% at 5 years, while those receiving an intestine with liver had graft survival of 57.8% at 1 year and 45.6% at 5 years (Figure IN 43). Among the analogous pediatric transplant recipients in 2016-2018, graft survival for intestine without liver was 76.1% at 1 year and 52.2% at 5 years and graft survival for intestine with liver was 81.1% at 1 year and 60.0% at 5 years (Figure IN 44). Those coming from nonmetropolitan areas in the entire 2016-2018 transplant cohort had slightly better graft survival than those coming from metropolitan areas, although the number of recipients from nonmetropolitan areas was quite small (Figure IN 45).

Rejection is frequently reported in the first posttransplant year, and approximately 20.0% of adult and pediatric recipients had acute rejection in the latest data. These most recent rejection rates are lower than those generally seen over the preceding decade (Figure IN 46).

In intestine transplant, PTLD has been frequently reported as a complication, perhaps due to the need for higher levels of immunosuppression compared with for other solid organ transplants and the higher proportion of pediatric recipients, who are more likely to be naive to Epstein-Barr virus (EBV) at the time of transplant. Five-year cumulative incidence of PTLD was 6.2% in those who received an intestine without liver (Figure IN 47) and 2.5% in those who received an intestine with liver (Figure IN 48). Among only those negative to EBV at transplant, 5-year cumulative incidence of PTLD was 11.5% in those who received an intestine without liver and 2.5% in those who received an intestine with liver.

Among adult recipients who underwent transplant in 2016-2018, those who received an intestine without liver had an overall survival of 89.8% at 1 year and 62.5% at 5 years. Those who received an intestine with liver had an overall survival of 62.2% at 1 year and 50.0% at 5 years (Figure IN 49). Among pediatric recipients who underwent transplant in 2016-2018, those who received an intestine without liver had an overall survival of 91.3% at 1 year and 78.3% at 5 years. Those who received an intestine with liver had an overall survival of 82.1% at 1 year and 65.3% at 5 years (Figure IN 50).