Medical Policy

This document addresses liver transplantation for individuals with end-stage liver disease. Donor livers may be obtained from deceased donors, in which a whole or partial (split) liver may be transplanted. Another source of donor organs is living donors, who are able to provide partial organs for transplantation.

Note: Please see the following for additional information:

• CG-TRANS-02 Kidney Transplantation
• TRANS.00013 Small Bowel, Small Bowel/Liver and Multivisceral Transplantation

Note: Members must meet the disease specific criteria as well as the general Individual Selection Criteria below for the transplantation to be considered medically necessary.

Medically Necessary:
A whole or partial liver transplant using a deceased or living donor is considered medically necessary for selected individuals with end-stage organ failure due to irreversible liver damage that includes, but is not limited to, the following conditions:

1. Cholestatic liver diseases:
   1. Primary biliary cirrhosis
   2. Primary sclerosing cholangitis
   3. Biliary atresia
   4. Caroli's disease
   5. Familial cholestasis
   6. Arteriohepatic dysplasia (Alagaille's disease)
   7. Cystic Fibrosis
2. Hepatocellular injury:
   1. Viral-induced Hepatitis
   2. Drug induced
      1. Acetaminophen
      2. Associated with halothane, gold, disulfram, others
   3. Alcohol induced
   4. Toxin exposure: Amanita mushroom poisoning
   5. Autoimmune hepatitis
3. Inborn errors of metabolism:
   1. Wilson's disease
   2. Organic acidurias
   3. Hemochromatosis
   4. Alpha-1 antitrypsin deficiency
   5. Homozygous type II hyperlipoproteinemia
   6. Crigler-Najjar Syndrome type I
   7. Protoporphyria
   8. Some urea cycle deficiencies
   9. Glycogen storage diseases types I and IV
   10. Tyrosine deficiency
   11. Citrullinemia
   12. Ornithine transcarboxylase deficiency
   13. Familial amyloid polyneuropathy (requires transplantation - polyneuropathy and cardiac amyloidosis development due to the production of a variant transthyretin molecule by the liver)
   14. Oxalosis (primary)
4. Acute Diseases:
   1. Fulminant hepatic failure
5. Mass Occupying Lesions:
   1. Hemangioendothelioma
   2. Hepatoblastoma confined to the liver
   3. Hilar cholangiocarcinoma (CCA) with a cross-sectional diameter 3 cm or less in conjunction with neoadjuvant chemoradiation therapy and the tumor is unresectable or there is underlying liver disease such that the individual is not a candidate for resection
   4. Polycystic disease of the liver (requiring transplantation due to the anatomic complications of a hugely enlarged liver)
   5. Primary hepatocellular carcinoma confined to the liver
6. Unresectable colorectal cancer with liver metastases (UCLM) in highly selected individuals when all of the following MELD/PELD exception criteria are met:
   1. Histological diagnosis of primary colon/rectal adenocarcinoma; and
   2. BRAF wild type, microsatellite stable; and
   3. 12 months or greater from time of UCLM diagnosis to time of initial request; and
   4. Resection of the primary tumor with negative margins; and
   5. No evidence of local recurrence by colonoscopy within 12 months prior to time of initial request; and
   6. No signs of extrahepatic disease or local recurrence based on imaging within 1 month of initial request; and
   7. Received or receiving first-line chemotherapy/immunotherapy; and
   8. Relapse of liver metastases after liver resection or liver metastases not eligible for curative resection; and
   9. No hepatic lesion(s) greater than 10 cm before start of treatment; and
   10. Must have stability or regression of disease with systemic and/or locoregional therapy for 6 months or greater.
7. Vascular disease:
   1. Budd-Chiari Syndrome
8. Other:
   1. Cryptogenic cirrhosis

Liver Retransplantation

Retransplantation in individuals with graft failure of an initial liver transplant, due to either technical reasons or hyperacute rejection is considered medically necessary.

Retransplantation in individuals due to either chronic rejection or recurrent disease is considered medically necessary when the individual meets general selection criteria as defined below.

Investigational and Not Medically Necessary:

Liver transplants in individuals with extrahepatic malignancy, including, but not limited to non-hilar extrahepatic cholangiocarcinoma, intrahepatic cholangiocarcinoma or hepatocellular carcinoma when either condition extends beyond the liver, are considered investigational and not medically necessary.
Liver transplants for all other conditions that do not lead to end-stage organ failure due to irreversible liver damage are considered investigational and not medically necessary.

Xenotransplantation is considered investigational and not medically necessary.

Bioartificial liver devices are considered investigational and not medically necessary.

Note: For multi-organ transplant requests, criteria must be met for each organ requested. In those situations, a member may present with concurrent medical conditions which would be considered an exclusion or a comorbidity that would preclude a successful outcome, but would be treated with the additional organ transplant. Such cases will be reviewed on an individual basis for coverage determination to assess the member's candidacy for transplantation.

General Individual Selection Criteria

In addition to having end stage liver disease, the member must not have a contraindication as defined by the American Society of Transplantation in Guidelines for the Referral and Management of Patients Eligible for Solid Organ Transplantation (2001) listed below.

Absolute Contraindications for Transplant Recipients include, but are not limited to, the following:

1. Metastatic cancer
2. Ongoing or recurring infections that are not effectively treated
3. Serious cardiac or other ongoing insufficiencies that create an inability to tolerate transplant surgery
4. Serious conditions that are unlikely to be improved by transplantation as life expectancy can be finitely measured
5. Demonstrated individual nonadherence, which places the organ at risk by not adhering to medical recommendations
6. Potential complications from immunosuppressive medications are unacceptable to the individual
7. Acquired immune deficiency syndrome (AIDS) (diagnosis based on Centers for Disease Control and Prevention [CDC] definition of CD4 count, 200 cells/mm³) unless the following are noted:
   1. CD4 count greater than 200 cells/mm³ for greater than 6 months
   2. HIV-1 RNA undetectable
   3. On stable anti-retroviral therapy greater than 3 months
   4. No other complications from AIDS (for example, opportunistic infection, including aspergillus, tuberculosis, coccidioidomycosis, resistant fungal infections, Kaposi’s sarcoma or other neoplasm)
   5. Meeting all other criteria for liver transplantation*

*Steinman, Theodore, et al. Guidelines for the Referral and Management of Patients Eligible for Solid Organ Transplantation. Transplantation. Vol. 71, 1189-1204, No. 9, May 15, 2001.

In 2022, liver transplants in the United States reached a record high of 9527, this reflected a 52% increase from 2012 to 2022. Of these, 93.7% were from deceased donors and 6.3% from living donors. Most were adults (94.5%), while pediatric recipients made up 5.5%. Alcohol-associated liver disease (ALD) was the primary diagnosis for 40.8% of adult transplants, followed by metabolic dysfunction-associated steatohepatitis (MASH) (19.9%), and other/unknown causes (14.5%). Hepatocellular carcinoma (HCC) was the primary diagnosis in 10.9% of cases, with cholestatic liver disease (7.1%), HCV (4.4%), and acute liver failure (2.3%) being less common. Additionally, 15.5% of recipients used HCC MELD exception points (Organ Procurement Transplant Network (OPTN)/Scientific Registry of Transplant Recipients (SRTR), 2023).

Liver Transplantation for End-Stage Organ Failure

In 2014, the American Association for the Study of Liver Diseases (AASLD) and the American Society of Transplantation (AST) issued joint guidelines on evaluation of adults for liver transplantation. The guidelines recommend liver transplantation for severe acute or advanced chronic liver disease after all effective medical treatments have been attempted. The formal evaluation should confirm the irreversible nature of the liver disease and lack of effective alternative medical therapy (AASLD, 2014).

The guidelines also stated that liver transplant is indicated for the following conditions:

• Acute liver failure complications of cirrhosis
• Liver-based metabolic condition with systemic manifestations
  • α1-Antitrypsin deficiency
  • Familial amyloidosis
  • Glycogen storage disease
  • Hemochromatosis
  • Primary oxaluria
  • Wilson disease
• Systemic complications of chronic liver disease.

The guidelines also included 1A recommendations (strong recommendation with high-quality evidence) for a liver transplant (LT) for:

• Patients with HIV infection are candidates for LT if immune function is adequate and the virus is expected to be undetectable by the time of LT.
• Candidates with HCV [hepatitis C virus] have the same indications for LT as for other etiologies of cirrhosis.

According to the AASLD many factors may affect the outcome of solid organ transplantation. Prior to transplantation the facility should complete an assessment of the individuals medical and psychosocial status to confirm that transplantation is the best treatment option for managing the individual’s disease and review of contraindications.

Potential Contraindications to Liver Transplant Include:

MELD [Model for End-stage Liver Disease] score < 15
Severe cardiac or pulmonary disease
AIDS
Ongoing alcohol or illicit substance abuse
Hepatocellular carcinoma with metastatic spread
Uncontrolled sepsis
Anatomic abnormality that precludes liver transplantation
Intrahepatic cholangiocarcinoma
Extrahepatic malignancy
Fulminant hepatic failure
Hemangiosarcoma
Persistent noncompliance
Lack of adequate social support system

In 2023, the American College of Gastroenterology (ACG) published Acute Liver Failure (ALF) Guidelines which note that etiology is an essential indicator for prognosis and treatment, especially regarding the necessity for liver transplantation (Shingina, 2023). The guideline also states that etiology is an independent predictor of waitlist mortality but not post-transplant outcomes. In individuals with ALF the ACG recommends using either the King's College criteria (KCC) or MELD score for liver transplant prognostication. Additionally, individuals meeting the KCC criteria or presenting with MELD > 25 are at high-risk of poor outcomes (conditional recommendation, strength of the recommendation is low).

Key concepts highlighted in the 2023 ACG guidelines include etiology specific management regarding liver transplant:

Mushroom poisoning: In patients presenting with mushroom poisoning and acute liver injury, Escudie criteria can be used to predict the need for liver transplantation even before the development of encephalopathy. Gastric lavage and activated charcoal should be administered within the first few hours after ingestion, provided no contraindications exist.

Wilson disease: In patients presenting with ALF due to suspected or confirmed Wilson disease, liver transplantation evaluation should be initiated during diagnosis because of the lack of effective medical therapy.

Autoimmune Hepatitis (AIH): In patients presenting with Acute Severe AIH, we suggest the use of IV corticosteroids. In patients with AS-AIH, which has progressed to ALF, we recommend early evaluation for liver transplantation.

Liver Transplantation for Alcohol Associated Liver Disease

The 2019 AASLD Guideline on Alcohol-associated Liver Disease provided recommendations on the timing of referral and selection of candidates for liver transplant. The guidance notes that the individual’s history of alcohol addiction is a primary driver in selecting appropriate candidates for liver transplantation. Decompensated alcohol-associated cirrhosis (AAC), Child-Pugh-Turcotte class C cirrhosis, or a MELD-Na score ≥ 21 should trigger an evaluation and consideration for liver transplantation. The authors suggest that candidate selection, "should not be based solely on a fixed interval of abstinence" and instead a formal psychological evaluation can help stratify individuals into higher-risk or lesser-risk strata for relapse.

The ACG echoed these recommendations in the 2024 Clinical Guideline for Alcohol-Associated Liver Disease which include:

18. Patients with complications of ALD cirrhosis should be referred for liver transplant when it is medically indicated.

21. In patients with severe alcoholic hepatitis (AH) who are unresponsive to medical management with high-risk of death, early liver transplantation for highly selected patients should be considered according to regional and institutional protocols (conditional recommendations, low level evidence ).

29. Selection for liver transplant in patients with ALD should not be based solely on an arbitrary period of sobriety. A detailed psychosocial evaluation by a social worker and addiction specialist should be used to inform the transplant teams-decision making (Jophlin et al, 2024).

Liver Transplant for Mass Occupying Lesions

In 2023, the AASLD published updated practice guidance on the prevention, diagnosis, and treatment of hepatocellular carcinoma. The recommendations regarding liver transplant include:

7.b. All patients listed for liver transplantation should undergo semiannual HCC surveillance because identification of early-stage HCC changes priority for transplantation (Level 3, Strong Recommendation).

33.c. Liver transplantation should be the treatment of choice for transplant-eligible patients with HCC that recur within Milan criteria after surgical resection (Level 3, Strong Recommendation).

34. AASLD advises the use of pre-transplant locoregional bridging therapy for patients being evaluated or listed for liver transplantation, if they have adequate hepatic reserve, to reduce the risk of waitlist dropout in the context of anticipated prolonged wait times for transplant (Level 3 strong recommendation).

Drefs (2024) published a meta-analysis of 63 studies involving 19,804 individuals to compare liver resection (n=11,626) and liver transplantation (n=8178) for HCC. The analysis found that liver transplantation was associated with higher 5-year overall survival (64.83%) and recurrence-free survival (70.20%) compared to liver resection (50.83% overall survival, p<0.001; 34.46% recurrence-free survival, p<0.001), respectively. The authors concluded that liver transplantation offers better long-term survival rates than liver resection for HCC.

The ACG Clinical Guideline for Focal Liver Lesions (Frenette, 2024) key concepts state:

18. Consideration for liver transplantation should be given to patients who meet the OPTN policy for transplantation, especially those with glycogen storage disease, unresctable beta-catenin positive adenoma, or unresectable with complications of hemorrhagic or malignant transformation of hepatic adenomas.

31. Patients with HCC, CCA, NET, and metastatic colon cancer that are within guidance consensus recommendations for liver transplant should be referred early in their course to a liver transplant center experienced in that disease process.

The National Comprehensive Cancer Network (NCCN^®) CPG (V2.2024) in Oncology^™ for hepatocellular carcinoma (HCC) provides a 2A recommendation for individuals meeting the “UNOS criteria ([AFP level ≤ 1000 ng/mL and single lesion ≥ 2 cm and ≤ 5cm, or 2 or 3 lesions ≥ 1 cm and ≤ 3cm,] should be considered for transplantation [cadaveric or living donation]).”

Liver transplantation should be considered only for highly selected individuals (for example, tumor ≤ 3 cm in radial diameter, no intrahepatic or extrahepatic metastases, no nodal disease) with either unresectable disease with otherwise normal biliary and hepatic function or underlying chronic liver disease precluding surgery.

The NCCN also states there are individuals whose tumor characteristics are marginally outside of the UNOS guidelines who should be considered for transplant. Furthermore, there are individuals who are down-staged to within criteria that can also be considered for transplantation. Candidates are eligible for a standardized MELD exception before completing locoregional therapy per the NCCN recommendations.

The NCCN Clinical Practice Guidelines (CPG) (V4.2024) in Oncology^™ for biliary tract cancers includes the following 2A recommendations regarding liver transplant for the treatment of extrahepatic cholangiocarcinoma (CCAs):

Before biopsy, evaluate if patient is a resection or transplant candidate. If patient is a potential transplant candidate, consider referral to transplant center before biopsy. Unresectable perihilar or hilar cholangiocarcinomas that measure ≤3 cm in radial diameter, with the absence of intrahepatic or extrahepatic metastases and without nodal disease, as well as those with primary sclerosing cholangitis, may be considered for liver transplantation at a transplant center that has an UNOS-approved protocol for transplantation of CCA. Surgery may be performed when index of suspicion is high; biopsy is not required.

There is retrospective evidence showing selected individuals with hilar CCA receiving preoperative chemoradiation therapy followed by liver transplantation have significantly improved overall survival compared with individuals undergoing resection. In 2022, the Liver and Intestinal Organ Transplantation OPTN committee updated the UNOS allocation of liver policy with MELD- exception criteria for liver transplant candidates with hilar CCA. Criteria includes standardized exception for candidates who have received neoadjuvant therapy prior to transplantation and present with cross-sectional imaging demonstrating a hilar mass measuring 3 cm or less in radial diameter.

In the recent NCCN CPG (V2.2024) in Oncology™ for neuroendocrine and adrenal tumors (NETs) the NCCN panel considers liver transplantation investigational for liver metastases of NETs of the gastrointestinal tract (well-differentiated grade 1/2). The panel’s recommendation is based on several series that reported results of liver transplantation in individuals with carcinoid tumors whose metastases were confined to the liver. The panel states:

Results from a multicenter database of 85 patients at 28 centers who underwent liver transplantation for NETs were also reported. A meta-analysis showed that, while 5-year survival rates are encouraging, the majority of patients undergoing liver transplantation ultimately develop recurrence. The panel acknowledged the considerable associated risks and deemed liver transplantation investigational and not part of routine care at this time.

Additionally, the NCI Gastrointestinal Neuroendocrine Tumors Treatment PDQ states:

In one prospective trial, 80 RFA sessions were performed in 63 patients with neuroendocrine hepatic metastases (including 36 carcinoids), and 92% of the patients reported at least partial symptom relief. In the same 63 patients, 70% had significant or complete relief at 1 week postoperatively, with a perioperative morbidity of 5%; duration of symptom control was 11 ± 2.3 months, and median survival time was 3.9 years after the first RFA. There are few trials of cryoablation of hepatic metastases, and the results of liver transplantation for metastatic disease are disappointing, reflecting the typically advanced disease states of transplant recipients (NCI, 2023).

Liver transplant for unresectable colorectal liver metastases (UCLM)

Individuals with UCLM have a poor prognosis. Liver resection is considered the only potentially curative treatment for individuals with CLM; however, palliative chemotherapy may be the only option for individuals with UCLM.

CLM has historically been considered an absolute contraindication for liver transplantation. The use of liver transplantation to treat UCLM in well selected individuals has been proposed. A number of prospective clinical trials evaluating this indication are currently underway. Liver transplantation has been performed in individuals with isolated (liver only) UCLM.

Hagness and colleagues (2013) published a prospective pilot study of liver transplantation for UCLM in 21 individuals without signs of extrahepatic disease. Inclusion criteria were; completed radical excision of the primary tumor, ECOG score 0 or 1, and minimum 6 weeks of chemotherapy. The absence of extrahepatic disease was confirmed by chest, abdominal, and pelvic CT scans, whole-body PET/CT scan, and bone scan. Exclusion criteria were weight loss of more than 10%, standard contraindications for liver transplantation, and the presence of other malignancies. After transplantation, participants had follow-up exams once a month the first year, every 3 months the second year, and every 6 months thereafter. Chest, abdominal, and pelvic CT scans were obtained every 3 months the first year, and thereafter every 6 months. Adjuvant chemotherapy was not given after liver transplantation. Disease-free survival was defined as the time from liver transplantation to metastatic or locoregional recurrence of disease or occurrence of a new colorectal tumor. The median follow-up was 27 months. Adverse events included 4 participants that had arterial complications: the first participant underwent retransplantation because of hepatic artery thrombosis (HAT) and subsequently anticoagulation was increased; HAT leading to retransplantation also occurred in a participant for whom the donor liver artery was very gracile and of poor quality; 2 additional arterial stenoses were caused by issues at the anastomoses. There were 5 reoperations because of hemorrhage, 1 hematoma, and 8 participants developed incisional hernia. The estimated overall survival was 95%, 68%, and 60% at 1, 3, and 5 years, respectively. Six of the participants died of  disseminated cancer after a median of 26 months post transplantation. Disease free survival was 35% at 1 year. Hepatic tumor load before transplantation, time from primary surgery to transplantation, and progressive disease on chemotherapy were prognostic indicators. The authors concluded that overall survival exceeds reported outcomes for chemotherapy alone, is comparable with liver resection for resectable CLM, as well as survival after repeat liver transplantation for nonmalignant diseases. Selection of individuals who receive transplant based on prognostic indicators may further improve outcomes. The consequences of the results of this study are limited based on the small number of participants, additionally the number of adverse events and reoperation are concerning.

The American Society of Clinical Oncology (ASCO) Resource-Stratified Guideline for the Treatment of Patients With Late-Stage Colorectal Cancer (2020) does not include a recommendation for liver transplantation. Recommendation #9 Liver-Directed Therapies in Patients With Metastatic Colorectal Cancer include:

5.1   Patients with liver metastases -Upfront surgery of metastases- Strength of Recommendation: Strong
5.2   Highly selected patients with liver metastases-Combination surgery and ablation- Strength of Recommendation: Moderate
5.3   Patients with liver metastases -Ablative therapies: radiofrequency, thermal, cryoablation, alcohol ablation, Radiation therapies: external-beam radiation, SBRT-Strength of Recommendation: Weak

In maximal settings, when patients are deemed to have unresectable liver metastases, depending on institutional expertise and after careful review by MDT, patients may receive/discuss the options of 5.4-5.6.

5.4    Patients with liver metastases-HAI of chemotherapy in combination with systemic chemotherapy. Qualifying statement: HAI therapy has limited availability in the United States and is used only in institutions with high level of expertise for this procedure and for select patients. Strength of Recommendation: Weak
5.5   Patients with liver metastases-TACE. Strength of Recommendation: Weak
5.6   Patients with liver metastases-SIRT in combination with systemic chemotherapy may be discussed to prolong time to liver disease progression in the second-line setting or beyond- Strength of Recommendation: Moderate

Puia and colleagues (2021) published a summary of eight ongoing trials studying liver transplantation for CLM using the Oslo score. The Oslo score evaluates the overall survival of liver transplantation candidates, giving one point for each of the following prognostic factors present:

• Tumors larger than 5.5 cm
• CEA over 80 μg/L
• Surgery of the primary less than 2 years before the liver transplantation
• Progression of metastases at the time of liver transplantation

The authors concluded that although recent results of liver transplantation for UCLM are encouraging, current data are based mostly on small, single center, heterogeneous studies. More robust studies with well controlled methodologies are needed.

Varley and colleagues (2021) published a meta-analysis of studies reporting liver transplantation for UCLM. Post-operative outcomes measured included 1-, 3-, and 5-year survival, OS, disease-free survival, and complication rates. Three non-randomised studies met the inclusion criteria, a total of 48 individuals received liver transplantation for UCLM. Survival at 1, 3, and 5 years was 83.3–100%, 58.3–80% and 50–80%, respectively (p=0.22, p=0.48, p=0.26). Disease-free survival was 35–56%. The authors concluded that current evidence suggests an encouraging survival benefit based upon this small population. Larger randomized studies with more long-term data to corroborate the findings are needed given the ethical implications of organ availability and allocation. Additionally, refinement of recipient selection criteria is needed to improve disease-free survival and overall survival.

In 2021 the International Hepato-Pancreato-Biliary Association published consensus guideline statements that standardized the nomenclature and provided an algorithm for recipient selection and organ allocation for liver transplantation in individuals with UCLM. Key principles identified were participant selection, evaluation of biological behavior, graft selection, recipient considerations, and outcomes (Booney, 2021).

The 2022 Treatment of Metastatic Colorectal Cancer ASCO Guideline recommendations for individuals with UCLM include the following:

Recommendation 6.1. Stereotactic body radiation therapy may be recommended following systemic therapy for patients with oligometastases of the liver who are not considered candidates for resection (Type: Evidence-based, benefits outweigh harms; Evidence quality: Low; Strength of recommendation: Weak).

Recommendation 6.2. Selective internal radiation therapy is not routinely recommended for patients with mCRC and unilobar or bilobar metastases of the liver (Type: Evidence-based, harms outweigh benefits; Evidence quality: Low; Strength of recommendation: Weak)

The guideline does not recommend evaluation for liver transplantation for individuals with UCLM.

Sasaki and colleagues (2023) published a study that summarized UNOS donor and recipient data, transplant center characteristics and post-transplant outcomes for liver transplantation as a treatment for UCLM. The groups included transplants for HCC with high-risk pathological characteristics, transplants for intrahepatic CCA/hilar CCA, and transplants for UCLM. From 2017 to 2022, 64 individuals were listed for UCLM in UNOS. Of the 64 individuals, 46 (71.9%) received LT, 8 (12.5%) were removed from the list, and 10 were still on the list. Of the 11 UNOS regions, all regions except 1 performed liver transplantation for UCLM during this period; 19 transplant centers listed individuals, and 15 centers performed liver transplantation for UCLM. Five centers performed 5 or more transplants for UCLM. During the study period, nearly 20 individuals with UCLM were listed in 2020 and 2021. The median age was 48 and 64.8% were male. Of the 46 individuals who underwent transplant, 26 (56.5%) received LDLT, and 20 received DDLT (43.5%). The median MELD-Na score was similar between the LDLT and DDLT groups (8 vs. 9, p=0.14). This persisted at the time of transplantation (8 vs. 12, p=0.06). The 1, 2, and 3 year, disease-free survival rates were 75.1, 53.7, and 53.7%. OS rates were 89.0, 60.4, and 60.4%, respectively. The authors concluded that this demonstrates a growing interest in high-volume transplant centers for liver transplantation as a therapeutic option for UCLM.

In 2024 the “Management of Locally Advanced Rectal Cancer: ASCO Guideline” was published. The guideline does not make any recommendations for liver transplantation.

OPTN published updated policy and guidance based upon the National Liver Review Board (NLRB) “Update Related to Transplant Oncology” (2024). As of this writing an implementation date has not been determined. The NLRB guidance states:

…unresectable colorectal liver metastases has a poor prognosis despite improved local and systemic treatments. Published studies support liver transplantation in highly selected patients and has demonstrated a survival benefit in initial prospective clinical trials. Based on currently available published studies, transplant programs should provide the following elements when submitting an initial MELD exception for CRLM:

Initial MELD Exception Criteria
Candidates can be considered for MELD exception points for CRLM if all of the following criteria are met:

Primary diagnosis:

• Histological diagnosis of colon/rectal adenocarcinoma
• BRAF wild type, microsatellite stable
• At least 12 months from time of CRLM diagnosis to time of initial exception request

Treatment of primary colorectal cancer

• Standard resection of the primary tumor with negative resection margins
• No evidence of local recurrence by colonoscopy within 12 months prior to time of initial exception request

Evaluation of extrahepatic disease

• No signs of extrahepatic disease or local recurrence, based on CT/MRI (chest, abdomen and pelvis) and PET scan within one month of initial exception request.

Evaluation of hepatic disease and prior systemic/liver directed treatment

• Received or receiving first-line chemotherapy/immunotherapy
• Relapse of liver metastases after liver resection or liver metastases not eligible for curative resection
• No hepatic lesion should be greater than 10 cm before start of treatment
• Must have stability or regression of disease with systemic and/or locoregional therapy for at least 6 months.

In cases of synchronous colon lesions, in addition to above criteria, all of the following are required:

• Resection of the primary tumor is performed more than 6 months after initial diagnosis
• Minimum of 6 months of chemotherapy after primary tumor resection before exception request with stability of disease for a total of at least 12 months after initial diagnosis.

Candidates meeting the criteria described should be considered for a MELD exception scores per Policy 9.4.E: MELD or PELD Exception Scores Relative to Median MELD or PELD at Transplant.

Candidates should not be considered for an initial MELD exception for CRLM if any of the following criteria are met:

• Extra-hepatic disease after primary tumor resection (including lymphadenopathy outside of the primary lymph node resection)
• Local relapse of primary disease
• Carcinoembryonic antigen (CEA) >80 µg/L with or without radiographic evidence of disease progression or new lesion.

Candidates with CRLM should be considered for a MELD exception extension if they continue to meet all of the following criteria:

• Every 3 months from initial MELD exception:
  • Perform CT or MRI (chest, abdomen and pelvis)
  • Perform CEA testing
• No progression of hepatic disease20
• No development of extrahepatic disease
• CEA < 80 µg/L

Additionally, in 2024 the National Cancer Institute provided the following update to the Colon Cancer PDQ^® for health professionals regarding treatment of Stage IV and recurrent colon cancer:

For patients with unresectable liver metastases, excellent outcomes have been achieved with liver transplant. The optimal patient cohort for this therapy is still being determined, but in general, the goal is to achieve good initial systemic control with chemotherapy, followed by transplant. In one study of 91 patients, 11% underwent live donor liver transplant. At a median follow-up of 1.5 years after transplant, the recurrence-free survival rate was 62% and the overall survival (OS) rate was 100%. [Level of evidence C3]

In the TRANSMET study (NCT02597348), published in abstract form, 94 patients were randomly assigned to receive either chemotherapy and liver transplant (n=47) or chemotherapy alone (n=47). In an intent-to-treat analysis, the 5-year overall survival (OS) rate was 57% in the chemotherapy-and-liver transplant arm and 13% in the chemotherapy-alone arm. In a per-protocol analysis, the 5-year OS rate was 73% in the chemotherapy-and-liver transplant arm and 9% in the chemotherapy-alone arm.[Level of evidence A1]

Subsequently, the TRANSMET multicenter, open-label, prospective, RCT was published by Adams in 2024. The trial investigated the comparative effects of curative-intent liver transplantation plus chemotherapy versus chemotherapy alone on OS in selected individuals with UCLM. Inclusion criteria for the study were: individuals aged 18-65 years with an ECOG performance status score of 0-1, histologically confirmed colorectal adenocarcinoma, BRAF wild-type, and confirmed permanent UCLMs by an independent validation panel. Participants needed to show an objective response (either stable disease or partial response for at least 3 months, with no more than 3 lines of therapy), have no extrahepatic disease as confirmed by CT scan and PET-CT imaging, and have undergone high-standard oncological surgical resection of the primary tumor. Additionally, there must be an absence of local recurrence on colonoscopy performed within 12 months before enrollment (unless the primary tumor resection occurred within the past 12 months), along with normal renal function, white blood cell count, and platelet levels. The exclusion criteria for the study included: general contraindications to LT, active alcohol or substance use disorder, active infection or uncontrolled sepsis, lack of psychosocial support or inability to comply with medical treatment, presence of other malignancies (either concomitant or within the past 5 years), failure to follow recommended guidelines for primary colorectal cancer surgery, having previous or concomitant extrahepatic metastases or local recurrence, and pregnancy. Participants in the study were randomized in a 1:1 ratio to receive either liver transplantation plus chemotherapy or chemotherapy alone. Those in the liver transplantation plus chemotherapy group underwent liver transplantation within 2 months after their last chemotherapy cycle. At the time of randomization, the liver transplantation plus chemotherapy group had received a median of 21 chemotherapy cycles, whereas the chemotherapy alone group had received 17 cycles, with treatment in up to three lines of chemotherapy. Transplanted participants were given immunosuppression and postoperative chemotherapy, while those in the chemotherapy group continued with their chemotherapy regimen. The primary outcome 5-year OS was analyzed in the ITT and per-protocol populations. Secondary outcomes were 3-year OS, 3-year and 5-year progression-free survival, 3-year and 5-year recurrence rate, and health-related quality of life. A total of 94 participants were randomly assigned and included in the ITT group, with 47 in the liver transplantation plus chemotherapy group and 47 in the chemotherapy alone group. Eleven participants in the liver transplantation plus chemotherapy group and 9 participants in the chemotherapy alone group did not receive the assigned treatment; therefore 36 and 38 participants in each group, respectively, were included in the per-protocol analysis. Participants had a median age of 54 years, and median follow-up was 59.3 months. In the ITT group, after a median follow-up of 59.3 months, 56 deaths had been reported. Median survival was not reached for the liver transplantation plus chemotherapy group and was 29.7 months (95% CI) in the chemotherapy group. In the ITT group, 5-year OS was 56.6% (95% CI) for liver transplantation plus chemotherapy and 12.6% for chemotherapy alone (HR 0.37 [95% CI]; p=0·0003) and 73∙3% (95% CI) and 9∙3%, respectively, for the per-protocol. Three participants underwent local ablation and 11 had radioembolization to increase local control. Serious adverse events occurred in 32 (80%) of 40 participants who underwent liver transplantation (from either group), 69 serious adverse events were observed in 45 (83%) of 54 participants treated with chemotherapy alone. Three participants in the liver transplantation plus chemotherapy group were retransplanted, 1 of whom died postoperatively of multi-organ failure. The estimated mean survival time up to 60 months was 43.9 months (95% CI) for the liver transplantation plus chemotherapy group and 31.3 months for the chemotherapy alone group, corresponding to a gain of 12.6 months (95% CI) 4.9−20.4 months; p=0·0014). In the intention-to-treat analysis, 3-year overall survival was 65.5% (95% CI) for the liver transplantation plus chemotherapy group and 38.9% for the chemotherapy alone group. In the per-protocol analysis, 5-year OS was 73.2% (95% CI, 59.6−90.0; 9 events) for the liver transplantation plus chemotherapy group and 9.3% (3.2–26.8; 33 events) for the chemotherapy alone group. Median survival was not reached for the liver transplantation plus chemotherapy group and was 26.6 months (95% CI) for the chemotherapy alone group (HR 0.16 [95% CI]; p<0.0001). The median secondary progression-free survival in the liver transplantation plus chemotherapy group was 35.4 months, with a 5-year secondary progression-free survival rate of 36.1% (95% CI). At the last follow-up in the per-protocol population, 15 (42%) of 36 participants in the liver transplantation plus chemotherapy group were alive without disease compared with 1 (3%) in the chemotherapy alone group. The authors concluded that in selected individuals with permanently unresectable CLMs, liver transplantation combined with chemotherapy and organ allocation priority improved survival compared to chemotherapy alone. 

The findings suggest that, based on society recommendations, current scientific literature, and input from relevant clinicians, liver transplantation may be a reasonable treatment option for individuals with permanently unresectable CLMs when clinical criteria are met.

Xenotransplantation

Xenotransplantation is any procedure that involves the transplantation, implantation, or infusion into a human recipient of either (a) live cells, tissues, or organs from a nonhuman animal source, or (b) human body fluids, cells, tissues, or organs that have had ex-vivo contact with live nonhuman animal cells, tissues, or organs. The development of xenotransplantation is, in part, driven by the fact that the demand for human organs for clinical transplantation far exceeds the supply. Although the potential benefits are considerable, the use of xenotransplantation raises concerns regarding the potential infection of recipients with both recognized and unrecognized infectious agents and the possible subsequent transmission to their close contacts and into the general human population. A particular public health concern is the potential for cross-species infection by retroviruses, which may be latent and lead to disease years after infection. Moreover, new infectious agents may not be readily identifiable with current techniques. At the present time xenotransplantation is considered investigational and not medically necessary.

Bioartificial liver device

A bioartificial liver device is a device that uses living liver cells housed in extracorporeal (outside the body) cartridges to provide temporary liver function. For some medical conditions, the device would be used to keep individuals alive and healthier until a transplantable liver becomes available. At this time there is limited scientific evidence available to support the safety and efficacy of this device and therefore bioartificial liver devices are considered investigational and not medically necessary.

A liver transplant consists of replacing an end-stage diseased liver with a healthy one. The liver is obtained from either a deceased or a living donor (a living donor gives only a segment of his/her liver to the recipient). In an orthotopic liver transplantation, the donor liver is placed in its correct anatomic location. A heterotopic liver transplantation refers to placement of the donor liver in a different location, typically with the native liver remaining in situ. The overwhelming majority of liver transplantations are orthotopic.

Split liver transplantation refers to dividing a donor liver into two grafts that can be used for two recipients. Generally, a pediatric recipient receives the left lobe and an adult recipient receives the right lobe.

Living-related donor transplantation of the left lateral segment primarily benefits children and is usually performed between parent and child. Adult-to-adult living donor transplantation uses the right lobe of the liver from a related or unrelated donor. Living donation allows the procedure to be scheduled electively, shortens the preservation time for the donor liver and allows time to optimize the recipient’s condition pre-transplant.

The limiting factor for liver transplantation is the short supply of donor organs. At the time of this writing, the procurement and distribution of organs for transplantation in the United States is under the direction of the UNOS. In 1990, UNOS established an organ allocation system based on the principles of medical urgency and local priority. In 2002, UNOS replaced the original liver allocation system with a new scoring system based on objective laboratory data, referred to as MELD/PELD (Pediatric End-stage Liver Disease). MELD is a numerical scale, ranging from 6 (less ill) to 40 (gravely ill) that is used for adults, giving each individual a score (number) based on how urgently they need a liver transplantation in the next 3 months. The number is calculated by a formula using bilirubin, prothrombin time, and creatinine. PELD considers a child’s bilirubin, prothrombin time, albumin, growth failure, and whether the child is less than 1 year old. In 2020 UNOS updated the transplant MELD or PELD exception extension policy; candidates can also receive additional points to increase their MELD/PELD score for conditions such as primary HCC, when tumors meet the modified Tumor-Node-Metastasis (TNM) staging classification. UNOS maintains a national database of transplant candidates, donors, recipients, donor-recipient matching, and histocompatibility (UNOS, 2022).

In 2021, the American Society of Transplant Surgeons (ASTS) Statement Concerning Eligibility for Solid Organ Transplant Candidacy noted:

The ASTS advocates transplanting as many of these patients, as quickly as possible, while also making the most responsible use of our nation’s organ supply. Limiting a transplanted organ’s life expectancy due to placing it with a patient, or in a situation, in which it cannot be adequately supported can deprive another waitlisted patient of a better outcome with the same organ.

To this end, we feel that any medically eligible patient, with sufficient support in place to allow for their adequate care following surgery, should be supported in their pursuit of transplantation.

When a patient presents to a transplant center for evaluation, the center makes a judgement concerning the patient’s medical fitness to undergo the procedure, and also the patient’s expected ability to capably care for themselves and a new organ.

If the patient has cognitive, physical, or financial limitations that would preclude them from being able to adequately care for themselves, then appropriate social supports or other compensatory mechanisms which would remediate the situation should be identified. If these can be found, then the patient’s candidacy for transplantation should be supported. If, however, they cannot be identified, proceeding with transplantation could threaten both the patient’s health and safety, and the longevity of a donated organ. In such a case, further evaluation should be deferred until the limiting issue can be corrected.

Cadaver: The physical remains of a deceased person.

End-stage: Being or occurring in the final stages of a terminal disease or condition.

Extrahepatic disease: Cancer that is located outside of the liver.

Fulminant liver failure: The onset of hepatic encephalopathy within 8 weeks of the first symptoms of liver disease.

Hepatoblastoma: A rare cancerous liver tumor occurring in infants and children that is composed of tissue resembling fetal or mature liver cells.

Heterotopic: Grafted or transplanted into an abnormal position.

In situ: In the natural or original position.

MELD: Model for End-Stage Liver Disease.

Neuroendocrine Tumors (NETs): A group of neoplasms that arise from cells of the neuroendocrine system. They have characteristics of both nerve cells and hormone-producing endocrine cells and can occur in various organs throughout the body, including the gastrointestinal tract, pancreas, lungs, and rarely in other sites like the adrenal glands or thyroid.

Orthotopic: Relating to the grafting of tissue in a natural position.

PELD: Pediatric end-stage liver disease.

Primary hepatocellular cancer: A cancer that originates within liver cells, as opposed to having spread to the liver from other organs.

Xenotransplantation: The surgical removal of an organ or tissue from an animal species and transplanting it into a human.

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member’s contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services may be Medically Necessary when criteria are met:

When services are Investigational and Not Medically Necessary:
For the procedure codes listed above when criteria are not met; or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

When services are also Investigational and Not Medically Necessary:

Peer Reviewed Publications:

1. Abecassis M, Adams M, Adams P, et al. Consensus statement on the live organ donor. JAMA. 2000; 284(22):2919-2926.
2. Abouna GJM. Emergency adult to adult living donor liver transplantation for fulminant hepatic failure-is it justifiable? Transplantation. 2001; 71(10):1498-1500.
3. Allen JW, Hassanein T, Bhatia SN. Advances in bioartificial liver devices. Hepatology. 2001; 34(3):447-455.
4. Adam R, Piedvache C, Chiche L, et al. Collaborative TransMet group. Liver transplantation plus chemotherapy versus chemotherapy alone in patients with permanently unresectable colorectal liver metastases (TransMet): results from a multicentre, open-label, prospective, randomised controlled trial. Lancet. 2024; 404(10458):1107-1118.
5. Bonney GK, Chew CA, Lodge P, et al. Liver transplantation for non-resectable colorectal liver metastases: the International Hepato-Pancreato-Biliary Association consensus guidelines. Lancet Gastroenterol Hepatol. 2021; 6(11):933-946.
6. Chamuleau RA. Bioartificial liver support. Metab Brain Dis. 2002; 17(4):485-491.
7. Ding YT, Qiu YD, Chen Z, et al. The development of a new bioartificial liver and its application in 12 acute liver failure patients. World J Gastroenterol. 2003; 9(4):829-832.
8. Drefs M, Schoenberg MB, Börner N, et al. Changes of long-term survival of resection and liver transplantation in hepatocellular carcinoma throughout the years: a meta-analysis. Eur J Surg Oncol. 2024; 50(3):107952.
9. Dumortier J, Czyglik O, Poncet G, et al. Eversion thrombectomy for portal vein thrombosis during liver transplantation. Am J Transplant. 2002; 2(10):934-938.
10. Efrati O, Barak A, Modan-Moses D, et al. Liver cirrhosis and portal hypertension in cystic fibrosis. Eur J Gastroenterol Hepatol. 2003; 15(10):1073-1078.
11. Emre S, Kitibayashi K, Schwartz ME, et al. Liver transplantation in a patient with acute liver failure due to sickle cell intrahepatic cholestasis. Transplantation. 2000; 69(4):675-676.
12. Frenette C, Mendiratta-Lala M, Salgia R, et al. ACG Clinical Guideline: Focal Liver Lesions. Am J Gastroenterol. 2024; 119(7):1235-1271.
13. Fridell JA, Bond GJ, Mazariegos GV, et al. Liver transplantation in children with cystic fibrosis: a long term longitudinal review of a single center's experience. J Pediatr Surg. 2003; 38(8):1152-1156.
14. Haberal M, Karakayali H, Emiroğlu R, et al. Living-donor split-liver transplantation. Transplant Proc. 2001; 33(5):2726-2729.
15. Hagness M, Foss A, Line PD, et al. Liver transplantation for nonresectable liver metastases from colorectal cancer. Ann Surg. 2013; 257(5):800-806.
16. Heimbach JK. Evolution of liver transplantation selection criteria and U.S. allocation policy for patients with hepatocellular carcinoma. Semin Liver Dis. 2020; 40:358-364.
17. Heimbach JK, Haddock MG, Alberts SR, et al. Transplantation for hilar cholangiocarcinoma. Liver Transpl. 2004; 10(10 Suppl 2):S65-68.
18. Huang KW, Chao A, Chou NK, Ko WJ. Hepatic encephalopathy and cerebral blood flow improved by liver dialysis. Int J Artif Organs. 2003; 26(2):149-151.
19. Jophlin LL, Singal AK, Bataller R, et al. ACG Clinical Guideline: Alcohol-Associated Liver Disease. Am J Gastroenterol. 2024; 119(1):30-54.
20. Kim-Schluger L, Florman SS, Gondolesi G, et al. Liver transplantation at Mount Sinai. Clin Transpl. 2000; Chapter 21:247-253.
21. Lim KJ, Keeffe EB. Liver transplantation for alcoholic liver disease: current concepts and length of sobriety. Liver Transpl. 2004; 10(10 Suppl 2):S31-38.
22. Mazzaferro V. Results of liver transplantation: with or without Milan criteria? Liver Transpl. 2007; 13(11 Suppl 2):S44-47.
23. Michler RE. Xenotransplantation: risks, clinical potential and future prospects. Emerg Infect Dis. 1996; 2(1):64-70.
24. Molmenti EP, Roodhouse TW, Molmenti H, et al. Thrombendvenectomy for organized portal vein thrombosis at the time of liver transplantation. Ann Surg. 2002; 235(2):292-296.
25. Molmenti EP, Squires RH, Nagata D, et al. Liver transplantation for cholestasis associated with cystic fibrosis in the pediatric population. Pediatr Transplant. 2003; 7(2):93-97.
26. Moreno-Gonzalez E, Meneu-Diaz JC, Garcia G, et al. Simultaneous liver-kidney transplant for combined renal and hepatic end-stage disease. Transplant Proc. 2003; 35(5):1863-1865.
27. Nair S, Verma S, Thuluvath PJ. Obesity and its effect on survival in patients undergoing orthotopic liver transplantation in the United States. Hepatology. 2002; 3591):105-109.
28. Nishizaki T, Ikegami T, Hiroshige S, et al. Small graft for living donor liver transplantation. Ann Surg. 2001; 233(4):575-580.
29. Pomfret EA, Pomposelli JJ, Lewis WD, et al. Live donor adult liver transplantation using right lobe grafts: donor evaluation and surgical outcome. Arch Surg. 2001; 13694):425-433.
30. Puia-Negulescu S, Lebossé F, Mabrut JY, et al. Liver transplantation for colorectal liver metastases: current management and future perspectives. Int J Mol Sci. 2021; 22(6):3093.
31. Rea DJ, Heimbach JK, Rosen CB, et al. Liver transplantation with neoadjuvant chemoradiation is more effective than resection for hilar cholangiocarcinoma. Ann Surg. 2005; 242(3):451-458; discussion 458-461.
32. Sakamoto S, Uemoto S, Uryuhara K, et al. Graft size assessment and analysis of donors for living donor liver transplantation using right lobe. Transplantation. 2001; 71(10):1407-1413.
33. Sasaki K, Ruffolo LI, Kim MH, et al. The current state of liver transplantation for colorectal liver metastases in the United States: a call for standardized reporting. Ann Surg Oncol. 2023; 30(5):2769-2777.
34. Sher LS, Levi DM, Wecsler JS, et al. Liver transplantation for metastatic neuroendocrine tumors: outcomes and prognostic variables. J Surg Oncol. 2015; 112(2):125-132.
35. Shingina A, Nizar M, Wakim-Fleming J et al. American Journal of Gastroenterology. Acute liver failure guidelines. Am J Gastroenterol. 2023; 118: 1128-1153.
36. Smith CM, Davies DB, McBride MA. Liver transplantation in the United States: a report from the organ procurement and transplantation network. Clin Transpl. 2000; Chapter 2:19-30.
37. Steinman TI, Becker BN, Frost AE, et al. Guidelines for the referral and management of patients eligible for solid organ transplantation. Transplantation. 2001; 71(9):1189-1204.
38. Sugawara Y, Makuuchi M, Takayama T, et al. Small-for-size grafts in living-related liver transplantation. J Am Coll Surg. 2001; 192(4):510-513.
39. Varley R, Tarazi M, Davé M, Mobarak S, et al. Liver transplantation for non-resectable liver metastases from colorectal cancer: a systematic review and meta-analysis. World J Surg. 2021; 45(11):3404-3413.

Government Agency, Medical Society, and Other Authoritative Publications:

1. American Association for the Study of Liver Disease (AASLD). Practice Guidelines. AASLD Guidelines for the treatment of hepatocellular carcinoma. 2018. Available at: https://www.aasld.org/sites/default/files/2022-06/HCC-Guideline-2018.pdf. Accessed on September 16, 2024.
2. American Association for the Study of Liver Diseases (AASLD). Practice Guidelines: Diagnosis and treatment of alcohol-associated liver diseases: 2019 practice guidance from the American association for the Study of Liver Diseases. Available at: https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/hep.30866. Accessed September 15, 2024.
3. American Association for the Study of Liver Diseases (AASLD). Practice Guidelines: Evaluation for liver transplantation in adults: 2013 practice guideline by the American Association for the Study of Liver Disease and the American Society of Transplantation. October 2014. Available at: https://www.aasld.org/practice-guidelines/evaluation-adult-liver-transplant-patient. Accessed on February 10, 2025.
4. American Association for the Study of Liver Disease (AASLD). Practice Guidelines. Evaluation of the pediatric patient for liver transplantation: 2014 practice guideline by the American Association for the Study of Liver Diseases, American Society of Transplantation and The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. October 2014. Available at: https://www.aasld.org/practice-guidelines/evaluation-pediatric-liver-transplant-patient. Accessed on February 10, 2025.
5. American Association for the Study of Liver Disease (AASLD). Practice guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. December 2023. Available at: https://journals.lww.com/hep/Citation/9900/AASLD_practice_guidance_on_prevention,_diagnosis,.441.aspx. Accessed on September 16, 2024.
6. American Society of Clinical Oncology. Management of Locally Advanced Rectal Cancer: ASCO Guideline. Updated August 8, 2024. J Clin Oncol. 2024: JCO2401160.
7. The American Society of Clinical Oncology Resource-Stratified Guideline for the Treatment of Patients With Late-Stage Colorectal Cancer. Updated October 17, 2022. Available at: https://ascopubs.org/doi/pdfdirect/10.1200/JCO.22.01690. Accessed on February 10, 2025.
8. American Society of Clinical Oncology. Treatment of Metastatic Colorectal Cancer: ASCO Guideline. Updated October 17, 2022. Available at: https://ascopubs.org/doi/10.1200/JCO.22.01690. Accessed on February 10, 2025.
9. American Society of Transplant Surgeons' position paper on adult-to-adult living donor liver transplantation. Liver Transplant 2000; 6(6):815-817.
10. American Society of Transplant Surgeons. ASTS statement concerning eligibility for solid organ transplant candidacy. Available at: https://www.asts.org/docs/default-source/position-statements/asts-statement-concerning-eligibility-for-solid-organ-transplant-candidacy.pdf?sfvrsn=1a6b4ed3_3. Accessed on February 10, 2025.
11. Centers for Medicare and Medicaid Services. National Coverage Determination. Available at: http://www.cms.hhs.gov/mcd/index_chapter_list.asp. Accessed on February 10, 2025.
    • Adult Liver Transplantation. NCD #260.1. Effective June 21, 2012.
    • Pediatric Liver Transplantation. NCD #260.2. Effective April 12, 1991.
12. NCCN Clinical Practice Guidelines in Oncology™ (NCCN). © 2025 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website at: http://www.nccn.org/index.asp. Accessed on February 12, 2025.
    • Biliary Tract Cancers: Version 4.2024. August 29, 2024.
    • Colon Cancer: Version 1.2025. February 7, 2025.Hepatocellular Carcinoma: Version 2.2024. July 2, 2024.
    • Neuroendocrine and Adrenal Tumors Version 2.2024. August 1, 2024.
13. Organ Procurement and Transplantation Network (OPTN) and Scientific Registry of Transplant Recipients (SRTR). OPTN/SRTR 2022 Annual data report. U.S. Department of Health and Human Services, Health Resources and Services Administration; 2024. Available at: Liver (hrsa.gov). Accessed on September 19, 2024.
14. United Network for Organ Sharing (UNOS). Organ Procurement and Transplantation Network. Policies: 9: allocation of livers and liver-intestines. Revised September 3, 2024. Available at: http://optn.transplant.hrsa.gov/governance/policies/. Accessed on September 16, 2024.
15. U.S. Department of Health and Human Services. Scientific Registry of Transplant Recipients (SRTR). Updated 2022. Available on: https://srtr.transplant.hrsa.gov/annual_reports/Default.aspx. Accessed on February 10, 2025.

1. American Cancer Society. Available at: https://www.cancer.org. Accessed on February 10, 2025.
2. John Hopkins Medicine. BRAF Mutation and Cancer. Available at: https://www.hopkinsmedicine.org/health/conditions-and-diseases/braf-mutation-and-cancer. Accessed on February 10, 2025.
3. National Cancer Institute. Available at: http://www.cancer.gov/cancertopics/types/alphalist. Accessed on February 10, 2025.
   • Adult primary liver cancer treatment Cancer (PDQ^®))-Health Professional Version. Updated May 9, 2024.
   • Colorectal Cancer Treatment (PDQ) Health Professional Version- Updated May 9, 2024
   • Gastrointestinal Neuroendocrine Tumors (PDQ^®)-Health Professional Version. Updated March 5, 2023.
4. National Institute of Diabetes and Digestive and Kidney Disease. Liver transplant. Last reviewed March 2017. Available at: https://www.niddk.nih.gov/health-information/liver-disease/liver-transplant. Accessed on September 16, 2024.
5. United Network for Organ Sharing. Available at: http://www.unos.org. Accessed on February 10, 2025.

Bioartificial Liver Device (BAL)
Liver Transplant: Orthotopic and Heterotopic
LIVERx 200™ Bioartificial Liver System
Sybiol^® Synthetic Bio-Liver Device
Transplant, Liver
Xenotransplantation

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

Federal and State law, as well as contract language, including definitions and specific contract provisions/exclusions, take precedence over Medical Policy and must be considered first in determining eligibility for coverage. The member’s contract benefits in effect on the date that services are rendered must be used. Medical Policy, which addresses medical efficacy, should be considered before utilizing medical opinion in adjudication. Medical technology is constantly evolving, and we reserve the right to review and update Medical Policy periodically.

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