Medical Policy: 07.03.05 

Original Effective Date: November 2009 

Reviewed: November 2018 

Revised: November 2018 

 

Benefit Application:

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.

 

Description:

This policy addresses transplantation of the 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. For isolated small bowel transplant see medical policy 07.03.04.

 

Combined Small Bowel and Liver Transplant

Combined small bowel and liver transplant is generally indicated when intestinal failure is accompanied by irreversible liver failure, usually due to the long term complications of total parenteral nutrition (TPN). 

 

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:

  • Short bowel syndrome following extensive bowel surgeries (midgut volvulus)
  • Congenital malformations (e.g. intestinal atresia, gastroschisis, aganglionosis)
  • Absorptive impairment (e.g. microvillus involution disease, chronic intestinal pseudo-obstruction)
  • Infections of gastrointestinal tract (e.g. necrotizing enterocolitis)

 

The following are the leading causes of intestinal failure in adults:

  • Crohn’s disease
  • Tumors of the mesenteric root and retroperitoneum (e.g. desmoid tumor)
  • Short bowl syndrome following extensive surgeries secondary to mesenteric ischemia (following thrombosis, embolism, volvulus or trauma)
  • Chronic intestinal pseudo-obstruction
  • Small bowel tumors such as Gardner’s Syndrome (familial colorectal polyposis)

 

The chronic use of TPN is often associated with life-threatening complication including:

  • Catheter related sepsis
  • Catheter related thrombosis
  • Severe dehydration
  • Parenteral nutrition associated liver disease (PNALD) 

 

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.  In some instances, short bowel syndrome is associated with liver failure, often due to long term complications of total parenteral nutrition (TPN).

 

Small Bowel/Liver Transplant or Multivisceral Transplant

A small bowel/liver transplant or a multivisceral transplant includes the small bowel and liver and one or more of the following organs: stomach and pancreas. The type of transplantation depends on the underlying etiology of intestinal failure, quality of native organs, presence or severity of liver disease, and history of prior abdominal surgeries. A multivisceral transplant is indicated when anatomic or other medical problems preclude a small bowel/liver transplant. Complications following small bowel/liver and multivisceral transplants include acute or chronic rejection, donor-specific antibodies, infection, lymphoproliferative disorder, graft versus host disease, and renal dysfunction.       

 

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 isolated small bowel transplantations.

 

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.    

 

Several investigators have reported higher survival rates in transplants 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. Although outcomes have improved over time, recurrent and chronic rejection and complications of immunosuppression continue to be obstacles of long term survival.

 

Several case series have focused on complications after small bowel and multivisceral transplantation:

 

  • Nagai et. al. (2016) reported on cytomegalovirus infection after intestinal or multivisceral transplant at a single center in the United States. Cytomegalovirus (CMV) infection is the most prevalent infectious complication after solid organ transplantation, and recipients of isolated intestinal transplantation (IIT)/multivisceral transplantation (MVT) are among those at the highest risk. Limited clinical data exist regarding CMV infection after IIT/MVT. The aim of this study was to analyze risk factors for post-transplant CMV infection and to assess the efficacy and validity of their prophylaxis and treatment regimens in intestinal transplantation. Medical records of 210 IIT/MVT patients were retrospectively reviewed. Post-transplant CMV prophylaxis regimen consisted of ganciclovir followed by 1 year of valganciclovir. The addition of CMV immunoglobulin (CMVIG) was decided according to donor/recipient CMV serostatus (D/R). All results of CMV PCR and/or pp65 antigenemia, and pathological reports were reviewed. Time to the incidence of CMV infection (viremia and/or tissue invasive disease) and risk factors for CMV infection were investigated. CMV infection was observed in 34 of 210 (16%) with a median onset of 347 days. Rejection was significantly associated with CMV infection (P = 0.01, odds ratio = 2.61). In the high-risk serostatus group (D+/R-), prophylactic CMVIG and induction with high-dose rabbit antithymocyte globulin (>10 mg/kg) were associated with a lower CMV infection rate on univariate analysis. The CMVIG remained to be an independent factor on multivariate analysis (P = 0.04, hazard ratio = 0.93/dose). Mortality associated with CMV infection occurred in 4, and CMV infection adversely affected patient survival (P = 0.001, hazard ratio = 2.71).
  • In 2016, Timpone et. al. performed retrospective review on all patients who underwent small intestine or multivisceral transplantation from November 8, 2003 through November 30, 2008. Those with Cytomegalovirus (CMV) viremia and invasive disease were identified. Intravenous ganciclovir (GCV) resistance was suspected in patients who continued to have viremic episodes or invasive disease despite appropriate GCV treatment. Genotypic analyses were performed to detect the presence of GCV resistance genes UL97 and UL54. During the study period, 88 small intestine or multivisceral transplants were performed on 85 patients. Of the 88 transplantations, 16 patients developed CMV viremia with or without end-organ disease (18.2%) and 5.7% developed GCV-R CMV infection. In patients diagnosed with CMV infection, 31.3% (5/16) had GCV-R CMV infection. Of patients with GCV-R CMV infection, 80% (4/5) developed CMV allograft enteritis, resulting in allograft explantation in 3 patients. All patients with GCV-R CMV infection were CMV donor positive/recipient negative. Patients with tissue-invasive CMV disease were 18 times more likely to be infected with GCV-R CMV (95% confidence interval 1.24-260.93; P-value 0.0341). The authors concluded, small intestinal and multivisceral transplant recipients have a higher rate of GCV-R CMV infection compared with other solid organ transplant recipients, which is often associated with tissue-invasive disease and allograft loss.
  • Wu et. al. (2016) investigated the incidence and risk factors of acute antibody-mediated rejection (ABMR) among patients undergoing intestinal transplantation (N=175). All patients were 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 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 and 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.   
  • In 2016, Cromvik et. al. investigated the incidence, clinical picture, risk factors and outcome of graft-versus-host disease (GVHD) in a cohort of patients who underwent intestinal or multivisceral tansplant. All transplanted patients (n = 26) were retrospectively analyzed with respect to donor- and recipient-derived risk factors. The diagnosis of GVHD was based on clinical signs, chimerism analyses of leukocytes, and histopathologic findings in biopsy specimens. Five of 26 patients (19%) were diagnosed with GVHD, of which three had skin GVHD, one had skin and bone marrow GVHD, and one had passenger leukocyte syndrome. Only multivisceral-transplanted patients developed GVHD. Risk factors for development of GVHD were an underlying tumor diagnosis and neoadjuvant chemo- or brachytherapy administered before intestinal transplantation. All patients were given high-dose corticosteroids as first line treatment for their GVHD, and all survived their episodes of GVHD. The authors concluded, the risk of GVHD appears to be increased in recipients of multivisceral transplantations who received chemotherapy due to an underlying malignancy. The reasons may be the large amount of lymphoid tissue in these types of grafts, and the cytotoxic effects of the malignancy and chemotherapy on healthy recipient tissues. These patients should be monitored closely for the development of GVHD.

 

Summary

For individuals who have intestinal failure and evidence of impending end-stage liver failure who receive a small bowel and liver transplant alone or multivisceral transplant, the evidence includes a limited number of case series. These transplant procedures are infrequently performed and few reported case series exist. However, results from the available case series have revealed fairly high post-procedural survival rates. Given these results and the exceedingly poor survival rates of patients who exhaust all other treatments, transplantation may prove not only to be the last option, but also a beneficial one. Transplantation is contraindicated for patients in whom the procedure is expected to be futile due to comorbid disease, or in whom post-transplantation care is expected to significantly worsen comorbid conditions. The evidence is sufficient to determine that the technology results in a meaningful improvement in net health outcomes.

Retransplantation

Evidence for the use of retransplantation to treat individuals who have failed intestinal transplantations includes several case series, mostly from single institutions. Among the case series reasons for retransplantations included: acute and chronic rejection, Cytomegalovirus (CMV), liver failure, lymphoproliferative disorder and graft. 

 

Lacaille et. al. (2017) reported on the achievements in pediatric intestinal transplantation (ITx) and define areas for improvement. After a period (1987-1990) of nine isolated small bowel transplants (SBTx) where only one patient survived with her graft, 110 ITx were performed on 101 children from 1994 to 2014: 60 SBTx, 45 liver-small bowel, four multivisceral (three with kidneys), and one modified multivisceral. Indications were short bowel syndrome (36), motility disorders (30), congenital enteropathies (34), and others (1). Induction treatment was introduced in 2000. Patient/graft survival with a liver-containing graft or SBTx was, respectively, 60/41% and 46/11% at 18 years. Recently, graft survival at 5/10 years was 44% and 31% for liver-containing graft and 57% and 44% for SBTx. Late graft loss occurred in 13 patients, and 7 of 10 retransplanted patients died. The main causes of death and graft loss were sepsis and rejection. Among the 55 currently living patients, 21 had a liver-containing graft, 19 a SBTx (17 after induction), and 15 were on parenteral nutrition. ITx remains a difficult procedure, and retransplantation even more so. Over the long term, graft loss was due to rejection, over-immunosuppression was not a significant problem. Multicenter studies on immunosuppression and microbiota are urgently needed. 

 

In 2018, Ekser et. al. reviewed and compared outcomes of intestinal retransplantation with primary intenstinal transplant (Itx), which included isolated ITx, modified multivisceral transplantation (mMVTx), and full MVTx, between 2003 and 2014 at Indiana University. Graft loss in intestinal transplantation (ITx) is close to 25% in the first year and 50% at 5-year post-transplantation. Although technically and immunologically challenging, intestinal retransplantation is now the 4th most common indication for ITx. Of 218 ITx, 18 (8.3%) were retransplantation. Causes of graft loss were rejection (78%), pancreatitis (11%), and severe intestine dismotility (11%). MVTx (16/18, 89%) was the preferred retransplantation option. In 7 (39%) patients, graftectomy was performed between primary and intestinal retransplantation. Median interval between primary ITx and retransplantation was 421 days. Although patient and graft survival rates at 1 year, 3 years, and 5 years were comparable between primary and retransplants, the number of retransplants was limited in the follow-up after post-transplant year 3. 

 

Summary

For individuals who have a failed small bowel and liver or multivisceral transplant without contraindications for retransplant who receive a small bowel and liver retransplant alone or multivisceral retransplant, the evidence includes case series. Although limited in quantity, the available post retransplantation data have suggested reasonably high survival rates. Given exceedingly poor survival rates without retransplantation of patients who have exhausted other treatments, evidence of postoperative survival from uncontrolled studies is sufficient to demonstrate that retransplantation provides a survival benefit in appropriately selected patients. Retransplantation is contraindicated for patients in whom the procedure is expected to be futile due to comorbid disease or in whom post-transplantation care is expected to significantly worsen comorbid conditions. The evidence is sufficient to determine that the technology results in a meaningful improvement in net health outcomes.

 

Practice Guideline and Position Statement

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:

  • Impending or overt liver failure as evidence by elevated serum bilirubin and/or liver enzymes, splenomegaly, thrombocytopenia, gastroesophageal varices, coagulopathy, stomal bleeding or hepatic fibrosis/cirrhosis
  • Thromobosis of major central venous channels (2 thromboses in subclavian, jugular or femoral veins) 
  • Frequent central line related sepsis (2 episodes of systemic sepsis secondary to line infection per year, 1 episode of line related fungemia, septic shock or acute respiratory distress syndrome (ARDS))
  • Frequent severe dehydration 

 

Until better data become available, these parameters are likely to be widely recognized as the indications for intestinal transplantation. 

 

American Society of Transplantation 

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.” 

Organ Procurement and Transplantation Network (OPTN)

In 2018, the Organ Procurement and Transplantation Network (OPTN) policies for allocation of liver and liver intestines and intestines are the following:  

 

Allocation of Livers and Liver-Intestines

Candidates awaiting a liver-intestine transplant who are registered and active on both waiting lists will automatically receive an additional increase in their MELD or PELD score equivalent to a 10 percentage point increase in risk of 3-month mortality. Candidates less than 18 years old will receive 23 additional points to their calculated MELD or PELD score instead of the 10 percentage point increase. The transplant hospital must document in the candidate’s medical record the medical justification for the combined liver-intestine transplant and that the transplant was completed.

 

Allocations of Livers
Status and Score Assignments

Each liver transplant candidate is assigned a score that reflects the probability of death within a 3-month period as determined by the Model for End-Stage Liver Disease (MELD) scoring system or the Pediatric End Stage Liver Disease (PELD) scoring system. Liver candidates can also be assigned a priority status if the candidate meets the requirements for that status.

 

Liver candidates at least 18 years old at the time of registration may be assigned any of the following:

  • Adult status 1A
  • Calculated MELD score
  • Exception MELD score
  • Inactive status  

 

Liver candidates less than 18 years old at the time of registration may be assigned any of the following:

  • Pediatric status 1A
  • Pediatric status 1B
  • Calculated MELD or PELD score
  • Exception MELD or PELD score
  • Inactive status 

 

Adult Status 1A Requirements

The candidate’s transplant program may assign the candidate adult status 1A if all the following conditions are met:

  1. The candidate is at least 18 years old at the time of registration 
  2. The candidate has a life expectancy without a liver transplant of less than 7 days and has at least one of the following conditions: 
    1. Fulminant liver failure, without pre-existing liver disease and currently in the intensive care unit (ICU), defined as the onset of hepatic encephalopathy within 56 days of the first signs or symptoms of liver disease, and has at least one of the following criteria:
      1. Is ventilator dependent
      2. Requires dialysis, continuous veno-venous hemofiltration (CVVH), or continuous veno-venous hemodialysis (CVVHD)
      3. Has an international normalized ratio (INR) greater than 2.0  
    2. Anhepatic 
    3. Primary non-function of a transplanted whole liver within 7 days of transplant, with aspartate aminotransferase (AST) greater than or equal to 3,000 U/L and at least one of the following:
      • International normalized ratio (INR) greater than or equal to 2.5
      • Arterial pH less than or equal to 7.30
      • Venous pH less than or equal to 7.25
      • Lactate greater than or equal to 4 mmol/L

      All laboratory results reported for the tests required above must be from the same blood draw taken 24 hours to 7 days after the transplant. 

    4. Primary non-function within 7-days of transplant of a transplanted liver segment from a deceased or living donor, evidenced by at least one of the following:
      1. INR greater than or equal to 2.5
      2. Arterial pH less than or equal to 7.30
      3. Venous pH less than or equal to 7.25
      4. Lactate greater than or equal to 4 mmol/L  
    5. Hepatic artery thrombosis (HAT) within 7-days of transplant, with AST greater than or equal to 3,000 U/L and at least one of the following: 
      • INR greater than or equal to 2.5 
      • Arterial pH less than or equal to 7.30 
      • Venous pH less than or equal to 7.25 
      • Lactate greater than or equal to 4 mmol/L

      All laboratory results reported for the tests required above must be from the same blood draw taken 24 hours to 7 days after the transplant.  

      Candidates with HAT in a transplanted liver within 14 days of transplant not meeting the above criteria will be listed with a MELD of 40.  

    6. Acute decompensated Wilson’s disease

 

Pediatric Status 1A Requirements

The candidate’s transplant program may assign the candidate pediatric status 1A if all the following conditions are met:

  1. The candidate is less than 18 years old at the time of registration. This includes candidates less than 18 years old at the time of registration, who remain on the waiting list after turning 18 years old, but does not include candidates removed from the waiting list at any time who then return to the waiting list after turning 18 years old.
  2. The candidate has at least one of the following conditions:  
    1. Fulminant liver failure without pre-existing liver disease, defined as the onset of hepatic encephalopathy within 56 days of the first signs and symptoms of liver disease and has at least one of the following criteria:
      1. Is ventilator dependent
      2. Requires dialysis, continuous veno-venous hemofiltration (CVVH), or continuous veno-venous hemodialysis (CVVHD)
      3. Has an international normalized ratio (INR) greater than 2.0  
    2. Diagnosis of primary non-function of a transplanted liver within 7 days of transplant, evidenced by at least two of the following:
      1. Alanine aminotransferase (ALT) greater than or equal to 2,000 U/L
      2. INR greater than or equal to 2.5
      3. Total bilirubin greater than or equal to 10 mg/dL
      4. Acidosis, defined as one of the following: 
        • Arterial pH less than or equal to 7.30 
        • Venous pH less than or equal to 7.25 
        • Lactate greater than or equal to 4 mmol/L 

      All laboratory results reported for any tests required for the primary non-function of a transplanted liver diagnosis above must be from the same blood draw taken between 24 hours and 7 days after the transplant.  

    3. Diagnosis of hepatic artery thrombosis (HAT) in a transplanted liver within 14 days of transplant  

    4. Acute decompensated Wilson’s disease

 

Pediatric Status 1B

The candidate’s transplant program may assign the candidate pediatric status 1B if all the following conditions are met:

  1. The candidate is less than 18 years old at the time of registration. This includes candidates less than 18 years old at the time of registration, who remain on the waiting list after turning 18 years old, but does not include candidates removed from the waiting list at any time who then return to the waiting list after turning 18 years old.   
  2. The candidate has one of the following conditions:  
    1. The candidate has a biopsy-proven hepatoblastoma without evidence of metastatic disease.  
    2. The candidate has an organic acidemia or urea cycle defect and a MELD or PELD exception score of 30 points for at least 30 days.  
    3. Chronic liver disease with a calculated MELD greater than 25 for adolescent candidates 12 to 17 years old, or a calculated PELD greater than 25 for candidates less than 12 years old, and has at least one of the following criteria:
      1. Is on a mechanical ventilator
      2. Has gastrointestinal bleeding requiring at least 30 mL/kg of red blood cell replacement within the previous 24 hours
      3. Has renal failure or renal insufficiency requiring dialysis, continuous veno-venous hemofiltration (CVVH), or continuous veno-venous hemodialysis (CVVHD)
      4. Has a Glasgow coma score (GCS) less than 10 within 48 hours before the status 1B assignment or extension.  
    4. Chronic liver disease and is a combined liver-intestine candidate with an adjusted MELD or PELD score greater than 25 according to Policy 9.1.F: Liver-Intestine Candidates and has at least one of the following criteria:
      1. Is on a mechanical ventilator
      2. Has gastrointestinal bleeding requiring at least 10 mL/kg of red blood cell replacement within the previous 24 hours
      3. Has renal failure or renal insufficiency requiring dialysis, continuous veno-venous hemofiltration (CVVH), or continuous veno-venous hemodialysis (CVVHD)
      4. Has a Glasgow coma score (GCS) less than 10 within 48 hours before the status 1B assignment or extension.

 

Meld Score

Candidates who are at least 12 years old receive an initial MELD score equal to:

 

0.957 x Loge(creatinine mg/dL) + 0. 378 x Loge(bilirubin mg/dL) + 1.120 x Loge (INR) + 0.643

 

Laboratory values less than 1.0 will be set to 1.0 when calculating a candidate’s MELD score.

 

The following candidates will receive a creatinine value of 4.0 mg/dL:

  • Candidates with a creatinine value greater than 4.0 mg/dL
  • Candidates who received two or more dialysis treatments within the prior 7 days
  • Candidates who received 24 hours of continuous veno-venous hemodialysis (CVVHD) within the prior 7 days  

 

The maximum MELD score is 40. The MELD score derived from this calculation will be rounded to the tenth decimal place and then multiplied by 10.

 

For candidates with an initial MELD score greater than 11, the MELD score is then re-calculated as follows:

 

MELD = MELD(i) + 1.32 (137-Na) – [0.033*MELD (137-Na)]  

 

Sodium values less than 125 mmol/L will be set to 125, and values greater than 137 mmol/L will be set to 137.

 

PELD Score

Candidates who are less than 12 years old receive a PELD score equal to:

 

0.436 (Age (<1 YR.)) – 0.687 x Loge (albumin g/dL) + 0.480 x Loge (total bilirubin mg/dL) + 1.857 x Loge (INR) +0.667 (Growth failure (<- 2 Std. Deviations present))

 

The PELD score derived from this calculation will be rounded to the tenth decimal place and then multiplied by 10.

 

Scores for candidates registered for liver transplantation before the candidate’s first birthday continue to include the value of 0.436 until the candidate is 24 months old.

 

Laboratory values less than 1.0 will be set to 1.0 when calculating a candidate’s PELD score.

 

A candidate has growth failure if the candidate is more than two standard deviations below the candidate’s expected growth based on age and gender using the most recent Centers for Disease Control and Prevention’s (CDC) National Center for Health Statistics pediatric clinical growth chart.

 

Allocation for Intestines

Each intestine candidate is assigned a status that reflects the candidate’s medical condition. Candidates may be assigned any of the following:

  • Status 1 
  • Status 2 
  • Inactive status

 

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:

  • Liver function test abnormalities 
  • No vascular access through the subclavian, jugular, or femoral veins for intravenous feeding 
  • Medical indications that warrant intestinal organ transplantation on an urgent basis

 

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.

 

Prior Approval:

 

Prior approval is required.

 

Policy:

A combined small bowel and liver transplant may be considered medically necessary for pediatric and adult patients when ALL of the following criteria is met:

  • Intestinal failure (characterized by loss of absorption and the inability to maintain protein-energy, fluid, electrolyte, or micronutrient balance) AND
  • Who have been managed with long-term total parenteral nutrition (TPN) AND one of the following:
    • Thrombosis of two or more major central venous channels (subclavian, jugular or femoral veins); OR
    • Frequent central line related sepsis
      • 2 or more episodes of line-induced systemic sepsis per year
      • 1 episode of line-related fungemia, septic shock or acute respiratory distress syndrome; OR 
    • Frequent episodes of dehydration despite total parenteral nutrition (TPN) and intravenous fluid supplement; AND  
  • Biopsy proven fibrotic changes within the liver indicating that the TPN associated liver dysfunction is irreversible; OR 
  • Clinical assessment of significant portal hypertension where biopsy may not be available or warranted or considered safe to perform. 

A multivisceral transplant may be considered medically necessary for pediatric and adult patients who meet criteria above for the combined small bowel and liver transplant and require 1 or more abdominal visceral organs to be transplanted due to concomitant organ failure or anatomical abnormalities that preclude a small bowel and liver transplant. 

 

A combined small bowel and liver transplant or multivisceral transplant for pediatric and adult patients performed for any other conditions not listed above will be considered not medically necessary.   

 

Retransplant

Retransplantation in individuals of a combined small bowel and liver transplant or multivisceral transplant to include non-function of the grafted organ(s), acute or chronic rejection, or return of disease may be considered medically necessary if the individual meets the criteria above.

 

Policy Guidelines

Potential contraindications to solid organ transplant are subject to judgement of the transplant center:

  • Known current malignancy, including metastatic cancer
  • Recent malignancy with high risk of recurrence
  • History of cancer with moderate risk of recurrence
  • Untreated systemic infection making immunosuppression unsafe, including chronic infection
  • Other irreversible end stage disease not attributed to intestinal failure
  • Systemic disease that could be exacerbated by immunosuppression
  • Psychosocial conditions or chemical dependency affecting ability to adhere to therapy  

 

 

Procedure Codes and Billing Guidelines:

  • To report provider services, use appropriate CPT* codes, Modifiers, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or diagnosis codes.
  • 44135 Intestinal allotransplantation; from cadaver donor
  • 47135 Liver allotransplantation; orthotopic, partial or whole, from cadaver or living donor, any age
  • 47399 Unlisted procedure, liver (this code may be used to represent liver allotransplantation; heterotopic, partial or whole, from cadaver or living donor, any age when performed in conjuction with small intestinal transplant or multivisceral transplant)
  • S2053 Transplantation of small intestine and liver allografts
  • S2054 Multivisceral transplant

 

Selected References:

  • Abu-Elmagd KM. Intestinal transplantation for short bowel syndrome and gastrointestinal failure: current consensus, rewarding outcomes, and practical guidelines. Gastroenterology. 2006 Feb; 130(2 Suppl 1): S132-7. 
  • American Gastroenterological Association. American Gastroenterological Association medical position statement: short bowel syndrome and intestinal transplantation. Gastroenterology. 2003 Apr;124(4):1105-10.
  • ECRI Institute. Hotline Response [database online]. Plymouth Meeting (PA): ECRI Institute 2008 Oct 21. Intestine and Intestine-Liver Transplantation.
  • Kato T, Tzakis AG, Selvaggi G et al. Intestinal and multivisceral transplantation in children. Ann Surg. 2006 Jun;243(6):756-64.
  • Bhagani S, Sweny P, Brook G; British HIV Association. Guidelines for kidney transplantation in patients with HIV disease. HIV Med. 2006; 7(3):133-9.
  • Sudan DL. Treatment of intestinal failure: intestinal transplantation. Nat Clin Pract Gastroenterol Hepatol. 2007 Sep;4(9):503-10.
  • Pironi L, Forbes A, Joly F et al. Survival of patients identified as candidates for intestinal transplantation: a 3-year prospective follow-up. Gastroenterology. 2008 Jul;138(1):61-71.
  • Tzvetanov IG, Oberholzer J, Benedetti E. Current status of living donor small bowel transplantation. Curr Opin Organ Transplant. 2010 Jun;15(3):346-8.
  • Gangemi A, Tzvetanov IG, Beatty E et al. Lessons learned in pediatric small bowel and liver transplantation from living-related donors. Transplantation. 2009 Apr 15;87(7):1027-30.
  • Gilroy R., Shapiro R., Intestinal and multivisceral transplantation. Medscape Reference 2012.May:2 (14)
  • American Gastroenterological Association Intestinal Transplantation for Gut Failure. June 2003. Volume 124, issue 6, pages 1516-1628.
  • American Society of Transplantation (AST). Facts About Intestinal Transplantation. December 2006.
  • Siego Nishida, M.D., PhD., Pediatric Intestinal and Multivisceral Transplantation. Medscape Reference May 30, 2012.
  • Centers for Medicare & Medicaid Services National Coverage Determination (NCD) for Intestinal and Multi-Visceral Transplantation (260.5).
  • Andreas G. Tzakis, M.D., PhD, et. al. 100 Multivisceral Transplants at a Single Center, Ann Surg 2005; 242:480-493
  • Matthew Wheeler, David Mercer, et. al. Department of Surgery, University of Nebraska Medical Center, Surgical Treatment of Intra-Abdominal Desmoid Tumors Resulting in Short Bowel Syndrome. Cancers 2012, 4, 31-38; doi:10.3390/cancers4010031
  • NCCN (National Comprehensive Cancer Network) Guidelines Version 2.2018 Soft Tissue Sarcoma. 
  • UpToDate. Desmoid Tumors: Systemic Therapy, Vinod Ravi, M.D., Shreyaskumar R. Patel, M.D., Topic last updated April 30, 2013.
  • UpToDate. Desmoid Tumors: Epidemiology, Risk Factors, Molecular Pathogenesis, Clinical Presentation and Local Therapy, Vinod Ravi, M.D., Shreyaskumar R. Patel, M.D., Chandrajit P. Raut, M.D., MSc, FACS, Thomas F. DeLaney, M.D., Topic last updated April 25, 2016.
  • UpToDate. Overview of Intestinal and Multivisceral Transplantation. Farrukh A. Khan, M.D., FACS, Gennaro Selvaggi, M.D., Topic last updated September 16, 2018.
  • Siego Nishida, M.D., PhD., Pediatric Intestinal and Multivisceral Transplantation, Medscape Reference Updated November 13, 2014.
  • Richard K. Gilroy, MBBS, FRACP, Intestinal and Multivisceral Transplantation, Medscape Reference Updated April 7, 2015.
  • Yildix Dogu Baris, Where Are We at With Short Bowel Syndrome and Small Bowel Transplant? World Journal of Transplantation, 2012 December 24;296):95-103
  • O’Keefe SJ, Buchman A, Fishbein TM. et.al. Short Bowel Syndrome and Intestinal Failure: Consensus Definitions and Overview. Clin Gastroenterol Hepatol. Jan 2006;4(1):6-10
  • Abu-Elmagd KM, Costa G, Bond GJ, et. al. Five Hundred Intestinal and Multivisceral Transplantations at a Single Center: Major Advances with New Challenges. Ann Surg. Oct2009;250(4):567-581
  • Mangus RS, Tector AJ, Kubal CA, et. al. Multivisceral Transplantation: Expanding Indications and Improving Outcomes. J Gastrointest Surg. Jan 2013;17(1):179-186
  • Trevizol AP, David AI, Yamashita ET. et.al. Intestinal and Multivisceral Retransplantation Results: Literature Review. Transplant Proc. Apr 2013;45(3):1133-1136Abu-Elmagd KM. Intestinal transplantation for short bowel syndrome and gastrointestinal failure: current consensus, rewarding outcomes, and practical guidelines. Gastroenterology. 2006 Feb; 130(2 Suppl 1): S132-7.
  • Lauro A, Zanfi C. Dazzi A, et. al. Disease-related intestinal transplant in adults: results from a single center. Transplant Proc. Jan-Feb 2014;46(1):245-248. PMID 24507060
  • Organ Procurement and Transplantation Network (OPTN) Policy 9 Allocation of Livers and Liver-Intestines. Effective October 2016.
  • Organ Procurement and Transplantation Network (OPTN) Policy 15 Identification of Transmissible Diseases Effective October 2016.
  • Blumberg E.A., Rogers C.C. The American Society of Transplantation Infectious Diseases Guidelines 3rd Edition, Human Immunodeficiency Virus in Solid Organ Transplantation. American Journal of Transplantation 2013 Volume 13, Issue s4, pages 169-178.
  • UpToDate. Chronic intestinal pseudo-obstruction. Michael Camilleri M.D.. Topic last updated July 18, 2016.
  • UpToDate. Management of short bowel syndrome in adults. John K DiBaise M.D. Topic last updated September 24, 2018. 
  • UpToDate. Management of short bowel syndrome in children. Danielle A. Stamm R.N., MSN, FNP-BC, Christopher Duggan M.D., MPH. Topic last updated July 13, 2018.
  • UpToDate. Gardner Syndrome. Randall W. Burt M.D.. Topic last updated January 6, 2015.
  • Lacaille F, Irtan S, Dupic L, et. al. Twenty-eight years of intestinal transplantation in Paris: experience of the oldest European center. Transpl Int. Feb 2017;30(2):178-186. PMID 27889929
  • Bharadwaj S, Tandon P, Gohel TD, et al. Current status of intestinal and multivisceral transplantation. Gastroenterol Rep (Oxf). Jan 26 2017. PMID 28130374
  • Loo L, Vrakas G, Reddy S, et al. Intestinal transplantation: a review. Curr Opin Gastroenterol. May 2017;33(3):203-211. PMID 28282321
  • Dore M, Junco PT, Andres AM, et al. Surgical rehabilitation techniques in children with poor prognosis short bowel syndrome. Eur J Pediatr Surg. Feb 2016;26(1):112-116. PMID 26535775
  • Rutter CS, Amin I, Russell NK, et al. Adult intestinal and multivisceral transplantation: experience from a single center in the United Kingdom. Transplant Proc. Mar 2016;48(2):468-472. PMID 27109980
  • Garcia Aroz S, Tzvetanov I, Hetterman EA, et al. Long-term outcomes of living-related small intestinal transplantation in children: A single-center experience. Pediatr Transplant. Jun 2017;21(4). PMID 28295952
  • Nagai S, Mangus RS, Anderson E, et al. Cytomegalovirus infection after intestinal/multivisceral transplantation: a single-center experience with 210 cases. Transplantation. Feb 2016;100(2):451-460. PMID 26247555
  • Timpone JG, Yimen M, Cox S, et al. Resistant cytomegalovirus in intestinal and multivisceral transplant recipients. Transpl Infect Dis. Apr 2016;18(2):202-209. PMID 26853894
  • Wu GS, Cruz RJ, Jr., Cai JC. Acute antibody-mediated rejection after intestinal transplantation. World J Transplant. Dec 24 2016;6(4):719-728. PMID 28058223
  • Cromvik J, Varkey J, Herlenius G, et al. Graft-versus-host disease after intestinal or multivisceral transplantation: a Scandinavian single-center experience. Transplant Proc. Jan-Feb 2016;48(1):185-190. PMID 26915866
  • Ueno T, Wada M, Hoshino K, et. al. Impact of Intestinal Transplantation for Intestinal Failure in Japan. Transplant Proc 2014 Jul-Aug;46(6):2122-4. PMID 25131121
  • Lauro A, Zanfi C, Dazzi A, et. al. Disease related intestinal transplant in adults: results from a single center. Transplant Proc. Jan-Feb 2014:46(1);245-248. PMID 24507060
  • Florescu DF, Qui F, Langnas AN, et. al. Bloodstream infections during the first year after pediatric small bowel transplantation. Pediatr Infect Dis J. Jul 2012;31(7):700-704. PMID 22466325
  • Florescu DF, Langnas AN, Grant W, et. al. Incidence, risk factors and outcomes associated with cytomegalovirus disease in small bowel transplant recipients. Pediatr Transplant. May 2012;16(3):294-301. PMID 22212495
  • Florescu DF, Islam KM, Grant W, et. al. Incidence and outcome of fungal infections in pediatric small bowel transplant recipients. Transpl Infect Dis. Dec 2010;12(6):497-504. PMID 20626710
  • Calvo Pulido J, Jimenz Romero C, Morales Ruiz E. et.al. Renal failure associated with intestinal transplantation: our experience in Spain. Traplant Proc. Jul-aug 2014;46(6):2140-2142. PMID 25131125
  • Boyer O, Noto C, De Serre NP, et. al. Renal function and histology in children after small bowel transplantation. Pediatr Transplant. Feb 2013;17(1):65-72. PMID 22882667    
  • Esker B, Kubal CA, Fridell JA. et. al. Comparable outcomes in intestinal retransplantation: Single-center cohort study. Clin Transplant 2018 Jul;32(7):e13290. PMID 29782661
  • Wu G, Selvaggi G, Nishida S, et. al. Graft-versus host disease after intestinal and multivisceral transplantation. Transplantation Jan 27 2011;91(2):219-224. PMID 21076376
  • Kaufmann SS, Atkinson JB, Bianchi A, et. al. Indications for pediatric intestinal transplantation: a position paper of the American Society of Transplantation. Pediatr Transplant 2001 Apr:5(2):80-7. PMID 11328544
  • Varkey J, Simren M, Bosaeus I, et. al. Surviavl of patients for intestinal and multivisceral transplantation the Scandinavian experience. Scan J Gastroenterol 2013 Jun:48(6);702-11. PMID 23544434

 

Policy History:

  • November 2018 - Annual Review, Policy Revised
  • November 2017- Annual Review, Policy Renewed
  • November 2016- Annual Review, Policy Revised
  • November 2015 - Annual Review, Policy Revised
  • December 2014 - Annual Review, Policy Revised
  • February 2014 - Annual Review, Policy Revised
  • March 2013 - Annual Review, Policy Revised
  • March 2012 - Annual Review, Policy Renewed
  • April 2011 - Annual Review, Policy Revised

Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.

 

*CPT® is a registered trademark of the American Medical Association.