OPTN/SRTR 2020 Annual Data Report: Intestine

Abstract

Despite small increases in additions to the intestine transplant waitlist, total waitlist numbers, overall intestine transplant rates, and overall transplants performed from 2019 to 2020, the trend over the last decade is still toward less intestine transplant activity. Waitlist mortality continues to fall for pediatric populations and is relatively stable for adults. While 1-year graft survival continues to improve, there has been no noticeable improvement in 3- and 5-year graft survival. Immunosuppression practices continue to favor use of an induction agent followed by tacrolimus-based regimens. Patient survival at 5 years is currently identical for isolated intestines and liver-inclusive allograft recipients.

Introduction

Clinical intestine transplant has been a reality for around 30 years and, as availability and outcomes have improved, the number of candidates and transplants steadily increased through the 1990s and early 2000s. The emergence of intestinal rehabilitation as a specific subspecialty, in large part due to the successes of intestinal transplant programs, has demonstrated that all but the most severe cases of intestinal failure can be managed with minimal mortality, short of transplant. However, intestine transplant alone or in combination with liver transplant and, potentially, other abdominal organs can be life sustaining and offers real improvements to the quality of life for many individuals.

Nonetheless, the trend for the last 12 or 13 years has been toward fewer listings and transplants, most notably, but not uniquely, among pediatric age-groups. It seems likely that these numbers will stabilize at some point, but with advances in intestinal failure care and no noticeable improvement in post-intestine transplant conditional graft survival beyond 1 year, the number of intestine transplants each year may decline further still.

The number of intestine transplants in adults now consistently exceeds that in infants, children, and adolescents, and the number of candidate listings for adults is approaching that of the pediatric candidates. Overall, there has been no change in the indications for intestine transplant, but even among those listed for transplant, medical care seems to be influential in that, despite increasing wait times, waitlist mortality continues to fall, again most notably for children.

Information on the waiting list, transplants, and outcomes is presented for both types of transplants, referred to as intestine-liver and intestine transplants, respectively. Both types include multivisceral transplants, distinguished by inclusion or exclusion of liver.

Waiting List

The number of additions to the intestine transplant waitlist in 2020 (144) increased over the previous year (103); however, the trend over the last decade has been toward fewer additions overall. The proportion of candidates listed for intestine with liver (80) or isolated intestine (64) remains relatively constant (Figure IN 1). Among the 370 prevalent patients on the waiting list at the end of 2020, 192 (51.9%) were waiting for intestine and 178 (48.1%) for intestine-liver transplant (Figure IN 2). The shift to an increasing proportion of adult candidates for intestine transplant compared with candidates younger than 18 continues; in 2020, 56.5% of candidates on the intestine waiting list were younger than 18, and adults accounted for 43.5% of the list (Figure IN 3). The racial/ethnic distribution remained relatively consistent over time; White patients represented 59% of those waiting for an intestine transplant in 2020 (Figure IN 5). The most common etiology of intestinal failure remained short-gut syndrome (SGS; >57%), which encompasses both congenital and non-congenital SGS, as well as necrotizing enterocolitis and, probably, a large proportion of the other/unknown group (Figure IN 6). Enteropathies and intestinal pseudo-obstruction syndromes are rare and account for less than 10% of all indications for listing for intestine transplant (Figure IN 6).

Characteristics of intestine and intestine-liver candidates on the waiting list at the end of 2020 were similar with respect to race and age; most were younger than 18 years and White (Table IN 1), but pediatric patients were more likely to be listed for intestine alone, whereas adults were more likely to be listed for combined intestine and liver. Intestine transplant candidates were 54.8% female, and intestine-liver candidates were 44.3% female. Considering disease etiology, congenital and non-congenital SGS were the leading causes of disease among intestine and intestine-liver transplant candidates (Table IN 2). Prevalent intestine-liver candidates had a medical urgency of Status 1 more often than intestine candidates (54.7% vs 35.7%; Table IN 2), and if listed for retransplant, most were listed for a liver-containing allograft (Table IN 3).

Although the largest proportion of candidates were on the waitlist for less than 90 days, this proportion has fallen over the decade, and 36% of listed patients remain on the waitlist for more than 2 years (Figure IN 7). The overall intestine transplant rate halved, from a peak of 80 transplants per 100 waitlist years in 2009 to 40 transplants per 100 waitlist years by 2012, and has remained around this level in recent years (Figure IN 9). Rates varied by candidate age and were lowest for those younger than 18 years (23.5 per 100 waitlist years) (Figure IN 10). Transplant rates are similar by transplant type (intestine, intestine-liver) (Figure IN 12).

Of the 88 candidates removed from the isolated intestine waiting list in 2020, 46 (52.3%) underwent deceased donor transplant, 4 (4.5%) died, 22 (25.0%) were removed from the list because their condition improved, and 2 (2.2%) were considered too sick to undergo transplant. No intestine transplants used a living donor allograft (Table IN 4, Table IN 5). Of outcomes for candidates listed for intestine transplant without liver in 2017, 69.4% underwent deceased donor transplant within three years, 3.4% died, 13.0% were removed from the list, and 14.2% were still waiting in 2020 (Figure IN 13). Likewise, 64 candidates were removed from the intestine-liver waiting list in 2020: 44 (68.8%) underwent deceased donor transplant, 9 (14.1%) died, 3 (4.7%) were removed from the list because their condition improved, and 3 (4.7%) were considered too sick to undergo transplant (Table IN 4, Table IN 5). Of intestine-liver candidates listed in 2017, 61.7% underwent deceased donor transplant within 3 years, 15.6% were removed from the list, 11.5% died, and 11.2% were still waiting in 2020 (Figure IN 14). Among candidates listed for intestine-liver transplant, median time to transplant saw a sizable increase, from 5.6 months for those listed in 2017-2018 to 13.5 for candidates listed in 2019-2020, whereas for isolated intestine candidates, the wait time for transplant was similar to that of previous eras, at 8.4 months (Figure IN 15).

The overall pretransplant mortality for intestinal transplant candidates was 6.5 deaths per 100 waitlist years in 2020 (Figure IN 16), and rates varied by age. Among candidates on the waiting list in 2020, pretransplant mortality was higher for adults (15.1 deaths per 100 waitlist-years) than for children (1.9 deaths per 100 waitlist-years) (Figure IN 17). Pretransplant mortality was higher for intestine-liver (10.6 deaths per 100 waitlist years) than for intestine transplant candidates (3.0 deaths per 100 waitlist years) (Figure IN 20).

Donation

Ninety-four intestines were recovered from deceased donors in 2020 (Figure IN 22). The highest proportion of intestine donors in 2020 were younger than 18 years (58.5%) (Figure IN 24). Most intestine donors were White (60.6%) (Figure IN 26). The overall rate of intestines recovered for transplant and not transplanted was 3.2% in 2020 (Figure IN 27). The most common cause of death among deceased intestine donors has always been head trauma, but in 2020, head trauma and anoxia each were the cause of death in 42.6% of intestine donors (Figure IN 29).

Transplant

The 91 intestine transplants performed in 2020 represented a small rise from 81 in 2019 (Figure IN 30), with 50 intestine-alone and 41 liver-inclusive transplants (Figure IN 31). The number of centers performing intestine transplants has remained relatively stable over the past decade (Figure IN 39). The median annual program volume was 3.5 intestine transplants in 2020; the 95th percentile of program volume was 18 transplants (Figure IN 40). In 2020, only slightly over half of intestine transplant programs performed 10 or more transplants per year, 40% performed three to nine transplants per year, and 9% of programs performed one or two transplant per year (Figure IN 41).

Throughout the 1990s and early 2000s, pediatric recipients of intestine transplants outnumbered adults; however, in the last decade, there were more adult recipients than children and adolescent recipients. Pediatric recipient counts declined from 94 in 2009 to 34 in 2020, while adult recipient counts only fell from 85 to 57 (Figure IN 32). In 2020, just over half of intestine-liver recipients were younger than 18 years (51.2% vs. 26.0% of intestine recipients) (Table IN 6). SGS was the main cause of disease leading to both intestine and intestine-liver transplant (Table IN 7). Most recipients of intestine-containing allografts in 2020 waited less than a year from listing to transplant (84% of intestine recipients and 78% of intestine-liver recipients) (Table IN 8).

Immunosuppression

Over the last decade, induction immunosuppression has been used in most intestine transplants (Figure IN 36). Tacrolimus remains the mainstay for maintenance immunosuppression, used in at least 73% of recipients, combined with corticosteroids (37.4%), mycophenolate mofetil (6.6%), or both (29.7%) (Figure IN 37).

Outcomes

For isolated intestine transplants, the clear trend over the last decade is toward improving 6- and 12-month graft survival. For transplants in 2019, only 3.3% of grafts had failed by 6 months and 6.7% by 1 year compared to 23.8% and 31.7% of transplants in 2009. However, such improvement has not been seen in 3- and 5-year graft failure, which remains consistently around 40% and 50%, respectively (Figure IN 42). Among intestine-liver transplant recipients, 42.1% had graft failure at 6 months and 47.4% at 1 year in 2019, 55.2% at 3 years in 2017, 69.0% at 5 years in 2015, and 75% at 10 years in 2010; there has been no consistent improvement in graft survival over the last 10 years for liver-inclusive allografts (Figure IN 43). For intestine transplants with or without a liver in 2013-2015, 1- and 5-year graft survival was 72.8% and 44.8%, respectively, for recipients 18 years or older and 76.0% and 61.3% for those younger than 18 years (Figure IN 44). One- and 5-year graft survival was 77.7% and 48.9%, respectively, for intestine recipients and 70.6% and 53.2%, respectively, for intestine-liver recipients (Figure IN 45). The number of recipients alive with a functioning intestine graft continued to increase, to 1217 on June 30, 2020, although we may be seeing a plateau, with essentially stable numbers of extant recipients in all groups but isolated intestine recipients younger than 18 years (Figure IN 47).

The incidence of first acute rejection in the first year posttransplant varied by age-group and transplant type. Among recipients in 2018-2019, incidence of acute rejection was highest in adult intestine recipients (41.2%) and lowest in adult intestine-liver recipients (35.4%) (Figure IN 48). For recipients in 2008-2018, 8.7% of intestine recipients (Figure IN 50) and 8% of intestine-liver recipients (Figure IN 51) developed posttransplant lymphoproliferative disorder within 5 years posttransplant, and rates varied by recipient and Epstein-Barr virus serostatus at transplant. Patient survival at 1 year for transplants in 2013-2015 was higher for recipients of an intestine alone (83.7% vs 75.6% for intestine-liver); however, by 5 years, the patient survival was identical, at 58.7% for both allograft types (Figure IN 52).

Figure List

Waiting list

Figure IN 1. New candidates added to the intestine transplant waiting list by liver co-listing
Figure IN 2. All candidates on the intestine transplant waiting list by liver co-listing
Figure IN 3. Distribution of candidates waiting for intestine transplant by age
Figure IN 4. Distribution of candidates waiting for intestine transplant by sex
Figure IN 5. Distribution of candidates waiting for intestine transplant by race
Figure IN 6. Distribution of candidates waiting for intestine transplant by diagnosis
Figure IN 7. Distribution of candidates waiting for intestine transplant by waiting time
Figure IN 8. Distribution of candidates waiting for intestine transplant by liver co-listing
Figure IN 9. Overall donor intestine transplant rates among waitlist candidates
Figure IN 10. Deceased donor intestine transplant rates among waitlist candidates by age
Figure IN 11. Deceased donor intestine transplant rates among waitlist candidates by race
Figure IN 12. Deceased donor intestine transplant rates among waitlisted adult candidates by liver co-listing
Figure IN 13. Three-year outcomes for candidates waiting for intestine transplant without liver, new listings in 2015-2017
Figure IN 14. Three-year outcomes for candidates waiting for intestine transplant with liver, new listings in 2015-2017
Figure IN 15. Median months to intestine transplant for waitlist candidates by liver co-listing
Figure IN 16. Overall pretransplant mortality rates among candidates waitlisted for intestine transplant
Figure IN 17. Pretransplant mortality rates among candidates waitlisted for intestine transplant by age
Figure IN 18. Pretransplant mortality rates among candidates waitlisted for intestine transplant by race
Figure IN 19. Pretransplant mortality rates among candidates waitlisted for intestine transplant by sex
Figure IN 20. Pretransplant mortality rates among candidates waitlisted for intestine transplant by liver co-listing
Figure IN 21. Overall deaths within six months after removal among intestine waitlist candidates

Deceased donation

Figure IN 22. Overall deceased intestine donor count
Figure IN 23. Deceased intestine donor count by age
Figure IN 24. Distribution of deceased intestine donors by age
Figure IN 25. Distribution of deceased intestine donors by sex
Figure IN 26. Distribution of deceased intestine donors by race
Figure IN 27. Overall percent of intestines recovered for transplant and not transplanted
Figure IN 28. Percent of intestines recovered for transplant and not transplanted by donor sex
Figure IN 29. Cause of death among deceased intestine donors

Transplant

Figure IN 30. Overall intestine transplants
Figure IN 31. Total intestine transplants by transplant type
Figure IN 32. Total intestine transplants by age
Figure IN 33. Total intestine transplants by sex
Figure IN 34. Total intestine transplants by race
Figure IN 35. Total intestine transplants by diagnosis
Figure IN 36. Induction agent use in intestine transplant recipients
Figure IN 37. Distribution of immunosuppression regimen use in intestine transplant recipients
Figure IN 38. Total HLA A, B, and DR mismatches among deceased donor intestine transplant recipients, 2016-2020
Figure IN 39. Number of centers performing adult and pediatric intestine transplants by center's age mix
Figure IN 40. Annual intestine transplant center volumes by percentile
Figure IN 41. Distribution of intestine transplants by annual center volume

Outcomes

Figure IN 42. Graft failure among transplant recipients of intestine without liver
Figure IN 43. Graft failure among transplant recipients of intestine with liver
Figure IN 44. Graft survival among deceased donor intestine transplant recipients, 2013-2015, by age
Figure IN 45. Graft survival among deceased donor intestine transplant recipients, 2013-2015, by transplant type
Figure IN 46. Graft survival among deceased donor intestine transplant recipients, 2013-2015, by metropolitan vs. non-metropolitan recipient residence
Figure IN 47. Recipients alive with a functioning intestine graft on June 30 of the year, by age at transplant and procedure
Figure IN 48. Incidence of acute rejection by 1 year posttransplant among intestine transplant recipients by age, 2017-2018
Figure IN 49. Incidence of acute rejection by 1 year posttransplant among intestine transplant recipients by induction agent 2017-2018
Figure IN 50. Incidence of PTLD among recipients of intestine transplant without liver by recipient EBV status at transplant, 2008-2018
Figure IN 51. Incidence of PTLD among recipients of intestine transplant with liver by recipient EBV status at transplant, 2008-2018
Figure IN 52. Patient survival among deceased donor intestine transplant recipients, 2013-2015, by transplant type

Table List

Waiting list

Table IN 1. Demographic characteristics of candidates on the intestine transplant waiting list on December 31, 2020
Table IN 2. Clinical characteristics of candidates on the intestine transplant waiting list on December 31, 2020
Table IN 3. Listing characteristics of candidates on the intestine transplant waiting list on December 31, 2020
Table IN 4. Intestine transplant waitlist activity, 2020
Table IN 5. Removal reason among intestine transplant candidates, 2020

Transplant

Table IN 6. Demographic characteristics of intestine transplant recipients, 2020
Table IN 7. Clinical characteristics of intestine transplant recipients, 2020
Table IN 8. Transplant characteristics of intestine transplant recipients, 2020

Table IN 1. Demographic characteristics of candidates on the intestine transplant waiting list on December 31, 2020
Candidates waiting for intestines with and without liver on December 31, 2020, regardless of first listing date. Distance is computed from candidate's home zip code to the transplant center.

Characteristic	IN, N	IN, Percent	IN-LI, N	IN-LI, Percent
Age: < 6 years	73	63.5%	49	46.2%
Age: 6-17 years	21	18.3%	20	18.9%
Age: 18-34 years	11	9.6%	26	24.5%
Age: 35-49 years	9	7.8%	11	10.4%
Age: 50-64 years	1	0.9%	0	0.0%
Sex: Female	63	54.8%	47	44.3%
Sex: Male	52	45.2%	59	55.7%
Race/ethnicity: White	65	56.5%	62	58.5%
Race/ethnicity: Black	22	19.1%	21	19.8%
Race/ethnicity: Hispanic	20	17.4%	20	18.9%
Race/ethnicity: Asian	5	4.3%	3	2.8%
Race/ethnicity: Other/unknown	3	2.6%	0	0.0%
Geography: Metropolitan	103	89.6%	80	75.5%
Geography: Non-metro	12	10.4%	26	24.5%
Distance: < 50 miles	27	23.5%	28	26.4%
Distance: 50-<100 miles	7	6.1%	12	11.3%
Distance: 100-<150 miles	7	6.1%	9	8.5%
Distance: 150-<250 miles	16	13.9%	16	15.1%
Distance: ≥ 250 miles	52	45.2%	33	31.1%
Distance: Unknown	6	5.2%	8	7.5%
All candidates	115	100.0%	106	100.0%

Table IN 2. Clinical characteristics of candidates on the intestine transplant waiting list on December 31, 2020
Candidates waiting for intestines with and without liver on December 31, 2020, regardless of first listing date. SGS, short-gut syndrome.

Characteristic	IN, N	IN, Percent	IN-LI, N	IN-LI, Percent
Diagnosis: Necrotizing enterocolitis	14	12.2%	5	4.7%
Diagnosis: Congenital SGS	23	20.0%	19	17.9%
Diagnosis: Non-congenital SGS	30	26.1%	36	34.0%
Diagnosis: Pseudo-obstruction	16	13.9%	2	1.9%
Diagnosis: Enteropathies	3	2.6%	4	3.8%
Diagnosis: Other/unknown	29	25.2%	40	37.7%
Blood type: A	40	34.8%	32	30.2%
Blood type: B	15	13.0%	10	9.4%
Blood type: AB	4	3.5%	2	1.9%
Blood type: O	56	48.7%	62	58.5%
IN medical urgency: Status 1	41	35.7%	58	54.7%
IN medical urgency: Non-urgent	31	27.0%	20	18.9%
IN medical urgency: Inactive	43	37.4%	28	26.4%
All candidates	115	100.0%	106	100.0%

Table IN 3. Listing characteristics of candidates on the intestine transplant waiting list on December 31, 2020
Candidates waiting for intestines with and without liver on December 31, 2020, regardless of first listing date.

Characteristic	IN, N	IN, Percent	IN-LI, N	IN-LI, Percent
Transplant history: First	105	91.3%	85	80.2%
Transplant history: Retransplant	10	8.7%	21	19.8%
Wait time: < 1 year	37	32.2%	41	38.7%
Wait time: 1-< 2 years	12	10.4%	15	14.2%
Wait time: 2-< 3 years	12	10.4%	11	10.4%
Wait time: 3-< 4 years	9	7.8%	11	10.4%
Wait time: 4-< 5 years	10	8.7%	5	4.7%
Wait time: ≥ 5 years	35	30.4%	23	21.7%
Tx type: Intestine only	97	84.3%	0	0.0%
Tx type: Intestine-liver	0	0.0%	1	0.9%
Tx type: Intestine-pancreas	15	13.0%	0	0.0%
Tx type: Intestine-pancreas-liver	0	0.0%	97	91.5%
Tx type: Intestine-pancreas-liver-kidney	0	0.0%	8	7.5%
Tx type: Other	3	2.6%	0	0.0%
All candidates	115	100.0%	106	100.0%

Table IN 4. Intestine transplant waitlist activity, 2020
Candidates listed at more than one center are counted once per listing. Candidates who are listed, undergo transplant, and are relisted are counted more than once. Candidates are not considered to be on the list on the day they are removed; counts on January 1 may differ from counts on December 31 of the prior year. Candidates listed for multi-organ transplants are included.

Waiting list state	IN	IN-LI
Patients at start of year	135	91
Patients added during year	65	82
Patients removed during year	88	64
Patients at end of year	112	109

Table IN 5. Removal reason among intestine transplant candidates, 2020
Removal reason as reported to the OPTN. Candidates with death dates that precede removal dates are assumed to have died waiting.

Removal reason	IN	IN-LI
Deceased donor transplant	46	44
Living donor transplant	0	0
Patient died	4	9
Patient refused transplant	1	0
Improved, transplant not needed	22	3
Too sick for transplant	2	3
Other	13	5

Table IN 6. Demographic characteristics of intestine transplant recipients, 2020
Intestine transplant recipients, including retransplants. Distance is computed from recipient's home zip code to the transplant center.

Characteristic	IN, N	IN, Percent	IN-LI, N	IN-LI, Percent
Age: < 18 years	13	26.0%	21	51.2%
Age: 18-34 years	14	28.0%	9	22.0%
Age: 35-49 years	13	26.0%	5	12.2%
Age: 50-64 years	9	18.0%	4	9.8%
Age: ≥ 65 years	1	2.0%	2	4.9%
Sex: Female	25	50.0%	14	34.1%
Sex: Male	25	50.0%	27	65.9%
Race/ethnicity: White	31	62.0%	22	53.7%
Race/ethnicity: Black	13	26.0%	12	29.3%
Race/ethnicity: Hispanic	4	8.0%	5	12.2%
Race/ethnicity: Asian	1	2.0%	2	4.9%
Race/ethnicity: Other/unknown	1	2.0%	0	0.0%
Insurance: Private	27	54.0%	16	39.0%
Insurance: Medicaid	7	14.0%	17	41.5%
Insurance: Unknown	16	32.0%	8	19.5%
Geography: Metropolitan	45	90.0%	31	75.6%
Geography: Non-metro	5	10.0%	10	24.4%
Distance: < 50 miles	22	44.0%	17	41.5%
Distance: 50-<100 miles	5	10.0%	3	7.3%
Distance: 100-<150 miles	4	8.0%	4	9.8%
Distance: 150-<250 miles	5	10.0%	4	9.8%
Distance: ≥ 250 miles	12	24.0%	12	29.3%
Distance: Unknown	2	4.0%	1	2.4%
All recipients	50	100.0%	41	100.0%

Table IN 7. Clinical characteristics of intestine transplant recipients, 2020
Intestine transplant recipients, including retransplants. SGS, short-gut syndrome. MELD scores are given for intestine-liver candidates.

Characteristic	IN, N	IN, Percent	IN-LI, N	IN-LI, Percent
Diagnosis: Necrotizing enterocolitis	1	2.0%	4	9.8%
Diagnosis: Congenital SGS	1	2.0%	7	17.1%
Diagnosis: Non-congenital SGS	31	62.0%	12	29.3%
Diagnosis: Pseudo-obstruction	5	10.0%	1	2.4%
Diagnosis: Other/unknown	12	24.0%	17	41.5%
Blood type: A	11	22.0%	16	39.0%
Blood type: B	8	16.0%	9	22.0%
Blood type: AB	1	2.0%	2	4.9%
Blood type: O	30	60.0%	14	34.1%
Medical condition: Hospitalized in ICU	0	0.0%	5	12.2%
Medical condition: Hospitalized, not ICU	5	10.0%	10	24.4%
Medical condition: Not hospitalized	43	86.0%	26	63.4%
Medical condition: Hospitalization unknown	2	4.0%	0	0.0%
IN medical urgency: Status 1	45	90.0%	32	78.0%
IN medical urgency: Non-urgent	5	10.0%	9	22.0%
LI medical urgency: Status 1A			7	17.1%
LI medical urgency: MELD/PELD ≥ 35			11	26.8%
LI medical urgency: MELD/PELD 30-34			7	17.1%
LI medical urgency: MELD/PELD 15-29			13	31.7%
LI medical urgency: MELD/PELD < 15			3	7.3%
All recipients	50	100.0%	41	100.0%

Table IN 8. Transplant characteristics of intestine transplant recipients, 2020
Intestine transplant recipients, including retransplants.

Characteristic	IN, N	IN, Percent	IN-LI, N	IN-LI, Percent
Wait time: < 31 days	10	20.0%	11	26.8%
Wait time: 31-60 days	3	6.0%	5	12.2%
Wait time: 61-90 days	7	14.0%	6	14.6%
Wait time: 3-< 6 months	10	20.0%	4	9.8%
Wait time: 6-< 12 months	12	24.0%	6	14.6%
Wait time: 1-< 2 years	5	10.0%	4	9.8%
Wait time: ≥ 2 years	3	6.0%	5	12.2%
Donor type: Deceased	50	100.0%	41	100.0%
Transplant history: First	46	92.0%	31	75.6%
Transplant history: Retransplant	4	8.0%	10	24.4%
Tx type: Intestine only	41	82.0%	0	0.0%
Tx type: Intestine-liver-pancreas	0	0.0%	35	85.4%
Tx type: Other	9	18.0%	6	14.6%
All recipients	50	100.0%	41	100.0%