Medical Policy: 07.03.04
Original Effective Date: November 2009
Reviewed: November 2020
Revised: November 2018
This policy contains information which is clinical in nature. The policy is not medical advice. The information in this policy is used by Wellmark to make determinations whether medical treatment is covered under the terms of a Wellmark member's health benefit plan. Physicians and other health care providers are responsible for medical advice and treatment. If you have specific health care needs, you should consult an appropriate health care professional. If you would like to request an accessible version of this document, please contact customer service at 800-524-9242.
Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.
This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.
For an intestinal allograft in combination with liver allograft, and multivisceral transplant which typically includes the small bowel/liver in combination with one or more other abdominal visceral organs such as the stomach and pancreas see medical policy 07.03.05 Small Bowel/Liver and Multivisceral Transplant*.
Solid organ transplantation offers a treatment option for patients with different types of end stage organ failure that can be lifesaving or provide significant improvements to a patient’s quality of life. Many advances have been made in the last several decades to reduce perioperative complications. Available data supports improvement in long-term survival as well as improved quality of life particularly for liver, kidney, pancreas, heart, and lung transplants. Allograft rejection remains a key early and late complication risk for any organ transplantation. Transplant recipients require life-long immunosuppression to prevent rejection. Patients are prioritized for transplant by mortality risk and severity of illness criteria developed by the Organ Procurement and Transplantation Network (OPTN) and United Network of Organ Sharing (UNOS).
A small bowel (intestinal) transplant may be performed as an isolated procedure. An isolated small bowel (intestinal)transplant has evolved into an established therapeutic modality in the management of the patient with irreversible intestinal failure. It is performed mainly in patients with short bowel syndrome (SBS) and those who develop severe complications due to total parenteral nutrition (TPN). The goal of transplantation is to eliminate the need for TPN and to reverse or prevent TPN associated liver disease.
Intestinal failure results from surgical resection, congenital defect or disease-associated loss of absorption and is characterized by the inability to maintain protein-energy, fluid, electrolyte, or micronutrient balance. Some conditions are more closely associated with pediatric intestinal failure while others are more common with intestinal failure in adults.
The following are pediatric conditions causing intestinal failure:
The following are adult conditions causing intestinal failure:
Short bowel syndrome is a condition in which the absorbing surface of the small intestine is inadequate due to extensive disease or surgical removal of a large portion of small intestine.
The small intestine, particularly the ileum, can adapt to some functions of the diseased or removed portion over a period of 1 to 2 years. Prognosis for recovery depends on the degree and location of the small intestine damage. Therapy is focused on achieving adequate macro and micro-nutrient uptake in the remaining small bowel. Pharmacologic agents have been studied to increase villous proliferation and slow transit times, and surgical techniques have been advocated to optimize remaining small bowel. However, some patients with short bowel syndrome are unable to obtain adequate nutrition from enteral feeding and become chronically dependent on total parenteral nutrition (TPN). Patients with complications from TPN may be considered candidates for small bowel transplant.
Total parenteral nutrition (TPN) is the current standard of care for patients with intestinal failure. The chronic use of TPN is often associated with life-threatening complications including:
Small bowel (intestinal) transplant should be recommended in patients with the following conditions:
Small bowel transplant may be considered a means to avoid end stage liver failure, thus avoiding a multivisceral organ transplant.
Intestinal transplants (including multivisceral and bowel/liver) represent a small minority of all solid organ transplants.
The purpose of a small bowel transplant in patients who have intestinal failure is to provide a treatment option that is an alternative to or an improvement on existing therapies.
The relevant population of interest are individuals with intestinal failure.
The therapy being considered is a small bowel transplant. Small bowel transplantation is provided in a hospital setting by specialized staff who are equipped to perform the surgical procedure and manage postsurgical intensive care.
The following practices are currently being used to make decisions about intestinal failure: medical management and parenteral nutrition.
The general outcomes of interest are overall survival (OS) and treatment related adverse events (e.g. immunosuppression, graft failure, surgical complications, infections). Short-term follow-up ranges from immediately post-surgery to 30 days post transplantation; lifelong follow-up (out to 10 years or more given current survival data) is necessary due to ongoing immunosuppression drugs and risk of graft failure.
Most of the published literature consists of case series, mainly reported by single centers in the United States, Japan and Europe. Many case series have included small bowel/liver transplantation and multivisceral transplantation which are the focus of the evidence review in medical policy 07.03.05.
Reasons for transplantation were mainly short bowel syndrome. Other reasons include congenital enteropathies and motility disorders. The most common outcomes reported were survival rates and weaning off TPN. Several studies have presented survival rates by type of transplantation, while others have combined all types of transplants when reporting survival rates. When survival rates were reported by type of transplant, isolated small bowel transplantation had higher survival rates than multivisceral transplants.
The number of patients who undergo an intestinal transplant is much lower than other forms of organ transplantation, and there are fewer centers that perform it. Several investigators have reported higher survival rates in transplantations conducted more recently than those conducted earlier. Reasons for improved survival rates in more recent years have been attributed to the development of more effective immunosuppressive drugs and the learning curve for the complex procedure. Graft survival in adult and pediatric patients is similar.
While outcomes have improved over time, recurrent and chronic rejection and complications of immunosuppression continue to be obstacles to long-term survival.
One issue discussed in intestinal transplantation literature is an earlier referral to avoid combined liver and intestine transplantation. It has been suggested that removing the restriction on intestinal transplantation to patients who have severe complications from TPN and recommending earlier transplantation may improve survival. However, in a review of the status of intestinal transplantation, no randomized trials that compared intestinal transplantation with long-term TPN; therefore, optimal timing for earlier transplantation has not been established.
In 2016, Wu et. al. investigated the incidence and risk factors of acute antibody-mediated rejection (ABMR) among patients undergoing intestinal transplantation (n=175). The mean age of enrolled patients was 25 years of age. Acute ABMR was diagnosed by clinical evidence; histologic evidence of tissue damage; focal or diffuse linear C4d deposition; and circulating anti-human leukocyte antigen antibodies. Of the 175 intestinal transplants, 58% were liver-free small intestine grafts, 36% included a liver graft, and 6.3% were retransplantations. Eighteen cases of acute ABMR were identified, 14 (14%) among the patients undergoing first liver-free transplantation, 2 (3%) among patients undergoing liver/small bowel transplantations, and 2 (18%) among the patients undergoing retransplantation. Graft failure occurred in 67% of patients with acute ABMR. The presence of a donor-specific antibody and a liver-free graft were associated with the development of acute ABMR.
Other case series have reported on renal failure after intestinal transplantation.
Cadaveric intestines are most commonly used, but recently there has been interest in using a portion of intestine harvested from a living related donor. Potential advantages of living donor include the ability to plan transplantation electively and better antigen matching, leading to improved management of rejection.
Most of the published literature consists of case series. In general survival rates of recipients with living donors are comparable to rates for recipients of cadaveric donations. Living related donors were reported to have an uneventful recovery. Weight loss and diarrhea were reported among donors, but recovery was without complications.
Small bowel transplant is infrequently performed compared to other forms of organ transplantation. Most of the published literature is case series mainly reported by single centers. Risks after small bowel transplant are high, particularly related to infection, but may be balanced against the need to avoid the long-term complications of total parenteral nutrition (TPN) dependence. In addition, early small bowl transplant may prevent the need for a later combined liver/small bowel transplant.
The purpose of small bowel retransplants in patients who have failed small bowel transplant and do not have contraindication(s) for retransplant is to provide a treatment option that is an alternative to or an improvement on existing therapies.
The relevant population of interest are individuals who have failed small bowel transplant and do not have contraindication(s) for retransplant.
The therapy being considered is a small bowel retransplant. Small bowel transplantation is provided in a hospital setting by specialized staff who are equipped to perform the surgical procedure and manage postsurgical intensive care.
The following practices are currently being used to make decisions about the intestinal failure of an initial small bowel transplant: medical management and parenteral nutrition.
The general outcomes of interest are overall survival (OS) and treatment related adverse events (e.g. immunosuppression, graft failure, surgical complications, infections). Short- term follow-up ranges from immediately post-surgery to 30 days post-transplantation; lifelong follow-up (out to 10 years or more given current survival data) is necessary due to ongoing immunosuppression drugs and risk of graft failure.
A few case series from single institutions and a single analysis of data from the United Network for Organ Sharing database have provided evidence on the use of retransplantation in patients who have failed primary small bowel transplant. The most common causes of graft loss in small bowel transplant are infection, rejection (acute and chronic) and technical or clinical complications. Careful patient selection, post-transplant immunosuppression and patient management are essential for successful long term outcomes.
Although the literature is limited in quantity, the available data have suggested reasonably high survival rates after small bowel retransplantation in patients who continue to meet all eligibility criteria for transplantation.
For individuals who have intestinal failure who receive a small bowel transplant, the evidence includes case series. Small bowel transplant is infrequently performed, and only relatively small case series, generally single-center, are available. Risks after small bowel transplant are high, particularly related to infection, but may be balanced against the need to avoid the long-term complications of total parenteral nutrition (TPN) dependence. In addition, early small bowel transplant may obviate the need for a later combined liver/small bowel transplant. Transplantation is contraindicated in patients in whom the procedure is expected to be unsuccessful due to comorbid disease or in whom post-transplantation care is expected to worsen comorbid conditions significantly. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.
For individuals who have failed small bowel transplant without contraindication(s) for retransplant who receive a small bowel retransplant, the evidence includes case series. Data from a small number of patients undergoing retransplantation are available. Although limited in quantity, the available data have suggested a reasonably high survival rate after small bowel retransplantation in patients who continue to meet criteria for transplantation. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.
In 2003, the American Gastroenterological Association produced a medical position statement on short bowel syndrome and intestinal transplantation. It recommends dietary, medical and surgical solutions. Indications for intestinal transplant mirror those of Medicare in patients who fail TPN therapy for one of the following reasons:
Until better data become available, these parameters are likely to be widely recognized as the indications for intestinal transplantation.
(Verified November 2020 this 2003 position statement remains as the current position statement)
In 2001, the American Society of Transplantation issued a position paper on indications for pediatric intestinal transplantation. The position paper included the following:
“Parenteral nutrition represents standard therapy for children with short bowel syndrome and other causes of intestinal failure. Most infants with short bowel syndrome eventually wean from parenteral nutrition, and most of those who do not wean tolerate parenteral nutrition for protracted periods. However, a subset of children with intestinal failure remaining dependent on parenteral nutrition will develop life-threatening complications arising from therapy. Intestinal transplantation can now be recommended for this select group. Life-threatening complications warranting consideration of intestinal transplantation include parenteral nutrition-associated liver disease, recurrent sepsis, and threatened loss of central venous access. Children with liver dysfunction should be considered for isolated intestinal transplantation before irreversible, advanced bridging fibrosis or cirrhosis supervenes, for which a combined liver and intestinal transplant is necessary. Irreversible liver disease is suggested by hyperbilirubinemia persisting beyond 3-4 months of age combined with features of portal hypertension such as splenomegaly, thrombocytopenia, or prominent superficial abdominal veins; esophageal varices, ascites, and impaired synthetic function are not always present.”
(Verified November 2020 this 2001 position remains as the current position statement)
In September 2020, the Organ Procurement and Transplantation Network (OPTN) policy for allocation of intestines includes the following:
Each intestine candidate is assigned a status that reflects the candidate’s medical condition. Candidates may be assigned any of the following:
To assign an intestine candidate status 1, the candidate’s transplant program must submit a Status 1 Justification Form to the OPTN Contractor. A candidate may be assigned status 1 if the candidate has any of the following conditions:
Any active candidate that does not meet the criteria for status 1 must be registered as status 2.
If the candidate is temporarily unsuitable for transplant, then the candidate’s transplant program may classify the candidate as inactive and the candidate will not receive any intestine offers.
Solid organ transplants are a surgical procedure and, as such, are not subject to regulation by the U.S. Food and Drug Administration (FDA).
The FDA regulates human cells and tissues intended for implantation, transplantation, or infusion through the Center for Biologics Evaluation and Research, under Code of Federal Regulation Title 21, parts 1270 and 1271. Solid organs used for transplantation are subject to these regulations.
Prior approval is required.
See related medical policy
A small bowel transplant using a cadaveric intestine may be considered medically necessary in adult and pediatric patients when ALL of the following criteria is met:
Small bowel transplant would be considered not medically necessary in adult or pediatric patients who do not meet the above criteria and/or are able to tolerate total parenteral nutrition(TPN).
Small bowel transplant using a living donor intestine may be considered medically necessary only when a cadaveric intestine is not available for transplantation in a patient who meets the above criteria for a cadaveric small bowel transplant.
Small bowel transplant using a living donor is considered not medically necessary in all other situations.
Retransplantation in individuals with failed prior small bowel transplant due to non-function of grafted organ, acute rejection requiring enterectomy (surgical removal of a portion of the intestine) or chronic rejection, or return of disease may be considered medically necessary if the individual meets the criteria for small bowel transplantation above.
The following potential contraindications to solid organ transplant are subject to judgement of the transplant center:
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