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AHCPR Health Technology Reviews. Rockville (MD): Agency for Health Care Policy and Research (US); 1992-1995. 

                        - This publication is provided for historical reference only and the information may be out of date.

**This publication is provided for historical reference only and the information may be out of date.**

## AHCPR Health Technology Reviews.

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Agency for Health Care Policy and Research (US)

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#  5Small Intestine and Combined Liver-Small Intestine Transplantation

S Steven Hotta, MD, PhD.

Published: August 1993.

## Report

The reacquisition of bowel functions by transplantation of the small intestines was                demonstrated to be technically feasible in dogs in 1966.(1). However, unlike the successful transplantation of the                hearth, lung, liver, and kidney, transplantation of the small bowel in humans was                unsuccessful through the 1980s, mainly because of the failure of immunosuppressive                therapy to prevent graft rejections and graft versus host disease.(2-5). Typically, reports described stormy postoperative courses for small                intestine graft recipients, with lengthy periods of intensive care before rejection                of the grafts. The substantial lymphoid components in the small intestines are                thought to contribute to making the control of immunological reactions that                generally occur between graft and host more difficult in small bowel transplant than                in other organ transplants. With the use of newer immunosuppressive agents, such as                FK 506, transplantation of the small intestine may show improved outcomes as is                currently being reported by investigators in Pittsburgh, PA.(6).

##                 Background

The first successful small intestine transplantation was performed by Goulet et                    al(7). in 1989; the recipient was a                5-month-old infant. After being successfully treated for episodes of rejection, the                infant was released from the hospital 10 months after surgery and was reported to be                on an enteral diet and growing normally 30 months after transplantation. The only                other report of successful small intestine transplantations was that by Todo et                    al.(6). Of the eight small intestines                transplanted, one failed at 22 months and the others were reported to be surviving                at 3 weeks to 5 months posttransplant. Four of the surviving recipients did not                require parenteral nutrition at 2 to 5 months posttransplant, while the other three,                at 1 month or less posttransplant, continued to be partially supported by parenteral                nutrition.

All recipients of small intestine transplants have had short-bowel syndromes as the                result of massive small bowel resections for conditions such as volvulus,                enterocolitis, Crohn's disease, mesenteric vascular disease, or trauma. These                patients had received total parenteral nutrition (TPN) for varying lengths of                time.

Many patients receiving TPN develop complications such as severe infections caused by                permanent intravenous catheters or metabolic disturbances of the liver caused by                parenterally administered nutrition. Some TPN recipients with signs of liver                dysfunction have received combined liver-small intestine grafts. Except for the                recent success reported for small intestine transplants, recipients of these                combined grafts appeared to have had better graft survival outcomes than those who                received only the small intestine grafts.(8,9). The possible protective                effect of the liver(10). was reminiscent                of findings in animal studies showing that a simultaneous liver graft seemed to                exert a protective effect that appeared to enhance the survival of other organ                    grafts.(11-13).

##                 Discussion

The first successful combined liver-small intestine transplantation in a patient was                reported in 1990 by Grant et al,(8). who                transplanted a combined graft into a 41-year-old woman who had a short-bowel                syndrome secondary to mesenteric thrombosis and had signs of liver failure as                manifested by an antithrombin III deficiency. Episodes of graft rejection and                transient acute graft versus host disease in the first few months posttransplant                were overcome by administration of immunosuppressant agents including cyclosporine                A, OKT3, steroid, and azathioprine. Two months after transplantation, the liver                showed no clinical or biochemical evidence of liver rejection and was functioning to                maintain liver enzyme values, bilirubin concentrations, and prothrombin times within                the normal range. Since the eighth week posttransplant, the patient's entire                nutrient, fluid, and electrolyte requirements were satisfied by an enteral diet. The                patient was discharged from the hospital 8 months after surgery, after recovering                from complications that resulted from a Hickman catheter infection, and was leading                a normal lifestyle that included an unrestricted oral diet a year after grafting. In                a subsequent report,(14). this patient was                again noted to be in good health and on a normal diet 23 months posttransplant. This                later report also described two additional liver-small intestine transplant                recipients, one of whom died 9 weeks posttransplant with biopsy-proved                cytomegalovirus enteritis. The other recipient was reported to be surviving and on a                normal diet 11 months posttransplant.

In Pittsburgh, eight patients underwent combined liver-small intestine                transplantation in 1990-1991.(6). All                recipients (two adults and six children) had advanced hepatic disease with elevated                serum total bilirubin concentrations and had been receiving TPN because of shortgut                syndrome. An infant recipient died 23 days posttransplant of sepsis and graft versus                host disease. The remaining seven recipients were reported to be well, at home, and                consuming normal oral diets 7-20 months posttransplant. Except for very brief                notations that liver-rejection episodes occurring in some of the patients were                treated successfully and that the livers resumed normal function before the grafted                    intestine,(15). none of the reports                presented any data to evaluate functional status of the transplanted livers in these                patients.

Recently a report from Wisconsin(16).                described a 14-month-old child with short-gut syndrome, cirrhosis, and variceal                bleeding, who received a combined liver-small intestine transplant. The child's                postoperative course was apparently satisfactory, and biopsy showed that the                intestines were histologically normal and viable. However, severe coagulopathy and                renal failure developed, and the patient died on the 52nd postoperative day.

##                 Summary

Recent published accounts of experiences with either small intestine or combined                liver-small intestine transplants indicate that both types of transplantations may                be feasible, with some expectation of successful outcome in terms of graft survival                and benefit to the patient. Clinical and outcome data for recipients of small                intestine transplants are presented in Table 1, and data for recipients of                combined liver-small intestine grafts are presented in Table 2. Only                the Pittsburgh group has reported successful transplantations and survival of                recipients of small intestine (eight patients, one graft failure) and combined                liver-small intestine transplants (eight patients, one death).(6). Aside from these patients, there have been reports of a                few other recipients with generally poorer outcomes at other transplant centers. In                Ontario, Canada, two of three patients who received combined liver-small intestine                grafts were reported to be surviving, and the only recipient of a small intestine                transplant died 10 weeks after surgery.(14). In Paris, France, of five patients who received small intestine grafts,                only one child is surviving with a functioning graft.(17). An unsuccessful combined liver-small intestine                transplantation was done at one other center,(16). and unsuccessful small intestine transplantations were attempted at                three other centers. (18-21). The total experience reported in the                literature numbers 18 small intestine transplantations with eight surviving,                functioning grafts. Twelve combined liver-small intestine transplantations have been                done, with nine recipients surviving with functional grafts. Perhaps with                improvements in immunosuppressive therapy, satisfactory long-term outcomes might be                expected. Although the results with the use of FK 506 reported from Pittsburgh are                encouraging, the small number of cases so far, the short period of follow-up, and                the lack of similar successful transplantation experiences at other transplant                centers preclude the ascertainment of whether transplantation of the small intestine                or the combined liver-small intestine is a generally beneficial treatment procedure                at this time. The short period of follow-up is of concern in view of the reported                failure of one of the grafts after 17 months and another after 22 months.

#### Table

Table 1. Small intestine transplantation. 

#### Table

Table 2. Combined liver-small intestine transplantation. 

##  References

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                        - Murase N, Demetris AJ, Kim DG, et al. Rejection of multivisceral allografts in rats: A sequential                        analysis with comparison to isolated orthotopic small-bowel and liver                        grafts.  Surgery.  1990;108:880–889. [PMC free article: PMC3032401] [PubMed: 2237770]
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                        - Deltz E, Mengel W, Hamelmann H. Small bowel transplantation: Report of a clinical                        case.  Prog Pediatr Surg.  1990;25:90–96. [PubMed: 2105524]
                        - 21.
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                        - Goulet O, Revillon Y, Brousse N, et al. Successful small bowel transplantation in an                        infant.  Transplantation.  1992;53:940–943. [PubMed: 1533072]
                        - 28.
                        - Casavilla A, Selby R, Abu-Elmagd K, et al. Logistics and technique for combined hepatic-intestinal                        retrieval.  Ann Surg.  1992;216(5):605–609. [PMC free article: PMC1242681] [PubMed: 1444653]
                        - 29.
                        - Abu-Elmagd K, Fung JJ, Reyes J, et al. Management of intestinal transplantation in                        humans.  Transplant Proc.  1992;24:1243–1244. [PMC free article: PMC2975453] [PubMed: 1376523]
                        - 30.
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                        - Grant D, Garcia B, Wall W, et. al. Graft-versus-host disease after clinical small bowel/liver                        transplantation.  Transplant Proc.  1990;22:–. [PubMed: 2264110]
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                        - Grant D, Wall W, Zhong R, et al. Experimental clinical intestinal transplantation: Initial                        experience of a Canadian center.  Transplant Proc.  1990;22:2497–2498. [PubMed: 2264124]
                        - 34.
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                        - 
AHCPR Pub. No. 93-0067

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Bookshelf ID: NBK63974

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