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
• TRANS.00039 Portable Normothermic Organ Perfusion Systems

Note: For a high-level overview of this document, please see “Summary for Members and Families” below. 

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 or perihilar cholangiocarcinoma (CCA) when all of the following are met:
      1. A cross-sectional diameter of 3 cm or less; and
      2. The individual has received locoregional or systemic therapy; and
      3. The tumor is unresectable or there is underlying liver disease such that the individual is not a candidate for resection; and
      4. The tumor is confined to the liver (absence of regional hepatic lymph node metastases, intrahepatic metastases, or extrahepatic disease).
   4. Biopsy proven intrahepatic cholangiocarcinoma (iCCA) or mixed hepatocellular carcinoma/intrahepatic cholangiocarcinoma (mixed HCC-iCCA) that is confined to the liver when all of the following are met:
      1. A cross-sectional diameter 3 cm or less; and
      2. Six months of tumor stability after locoregional or systemic therapy; and
      3. The tumor is unresectable or there is underlying liver disease such that the individual is not a candidate for resection.
   5. Polycystic disease of the liver (requiring transplantation due to the anatomic complications of a hugely enlarged liver)
   6. 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. Neuroendocrine tumors (NETs) of gastro-entero-pancreatic (GEP) origin when both of the following are met:
   1. Resection of primary malignancy and extrahepatic disease without evidence of recurrence for greater than or equal to 6 months; and
   2. There is no evidence of extrahepatic metastases and neuroendocrine liver metastases is limited to the liver, bi-lobar, not amendable to resection.
8. Vascular disease:
   1. Budd-Chiari Syndrome
9. 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 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. Ongoing or recurring infections that are not effectively treated
2. Serious cardiac or other ongoing insufficiencies that create an inability to tolerate transplant surgery
3. Serious conditions that are unlikely to be improved by transplantation as life expectancy can be finitely measured
4. Demonstrated individual nonadherence, which places the organ at risk by not adhering to medical recommendations
5. Potential complications from immunosuppressive medications are unacceptable to the individual
6. 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.

This document describes clinical studies and expert recommendations, and explains whether liver transplantation is appropriate. The following summary does not replace the medical necessity criteria or other information in this document. The summary may not contain all of the relevant criteria or information. This summary is not medical advice. Please check with your healthcare provider for any advice about your health.

Key Information

Liver transplantation is a surgery used to replace a damaged liver with a healthy one. The new liver can come from a person who has died or from a living person who donates part of their liver. This procedure is mainly for people with serious liver disease that cannot be reversed. Sometimes, a second liver transplant (retransplantation) may be needed if the first one fails. Transplantation may also be considered in some people with certain types of liver cancer or other rare liver problems, but only under strict conditions. Some new types of treatment, like using animal organs (xenotransplantation) or liver devices made with living cells (bioartificial liver devices), are still being studied and are not part of routine care. Experts agree that each person must be carefully checked to make sure the transplant is likely to help and that they are healthy enough to go through with the surgery and recover well. Transplant centers also follow strict rules to decide who gets a liver, based on how sick they are and how much the transplant may help.

What the Studies Show

Liver transplants can help people with many types of serious liver disease live longer and feel better. They are also used for some cancers. Studies show better survival and lower recurrence for some cancers like hepatocellular carcinoma (HCC) when treated with transplant instead of tumor resection or other treatment. In selected cases of colorectal cancer that has spread only to the liver, liver transplantation has shown promising results when other treatments have failed. High-quality studies show longer survival for individuals with colorectal cancer that has spread only to the liver who received transplants plus chemotherapy compared to those who got chemotherapy alone. However, more research is needed to confirm these findings. For certain rare tumors like neuroendocrine tumors (NETs), some research shows benefit. Newer approaches like bioartificial liver devices or using animal organs have not been proven to work and may carry serious risks, including infections.

When is Liver Transplant Clinically Appropriate?

Liver transplant may be appropriate in these situations:

• The person has irreversible liver damage caused by diseases like hepatitis, alcohol-related liver disease, autoimmune hepatitis, or inherited conditions such as Wilson’s disease or cystic fibrosis.
• They have liver cancer that is small and has not spread, such as HCC, or rare tumors like hemangioendothelioma or hepatoblastoma, under strict conditions.
• They have certain types of bile duct cancer (cholangiocarcinoma) or mixed liver cancers that meet specific size and stability rules.
• They have colorectal cancer that has spread only to the liver, and all of these conditions are met: tumor is under control, no spread outside the liver, 12 months have passed since diagnosis, and standard treatments have been tried.
• They need a second transplant due to failure of a previous one, and they meet the general selection criteria.

When is this not Clinically Appropriate?

Liver transplant is not appropriate when cancer has spread outside the liver or when tumors are too large or aggressive. This is because studies show that people with these conditions do not do well after transplant. Transplants are also not appropriate for conditions that do not cause serious liver failure. Using animal organs or bioartificial liver devices has not been proven to improve health. These options are considered investigational because they have not shown clear benefits in studies. Liver transplant is not clinically appropriate in scenarios other than those listed above.

(Return to Description/Scope)

Summary:

This document addresses liver transplantation for individuals with end-stage liver disease, including transplantation using whole or partial grafts from deceased or living donors, as well as indications for retransplantation. The evidence base includes large registry data, observational studies, meta-analyses, and selected randomized and prospective trials demonstrating that liver transplantation improves survival and quality of life across a range of irreversible liver diseases, selected primary hepatic malignancies, and highly selected cases of unresectable colorectal liver metastases. The document also reviews emerging but limited evidence for novel indications and confirms insufficient evidence for xenotransplantation and bioartificial liver devices. Professional guidance referenced in the Discussion and Rationale includes recommendations from the American Association for the Study of Liver Diseases (AASLD), American Society of Transplantation (AST), American College of Gastroenterology (ACG), American Society of Clinical Oncology (ASCO), National Comprehensive Cancer Network (NCCN), American Society of Transplant Surgeons (ASTS), and guidance from the Organ Procurement and Transplantation Network (OPTN), including National Liver Review Board (NLRB) evaluative guidance for MELD exception requests. Collectively, these sources support individualized candidate evaluation based on disease severity, transplant benefit, and clinical context rather than reliance on a single scoring system.

Discussion:

In 2023, liver transplants in the U.S. reached a record high of 10,659 procedures, comprising 10,125 adult (95.0%) and 534 pediatric (5.0%) recipients, representing a 52% increase since 2012. The majority of transplants were from deceased donors (93.7%), with living donors accounting for 6.3% overall. Growth was driven by increased use of older donors and donation after circulatory death (DCD) donors, supported by broader adoption of machine perfusion technologies. The liver nonuse rate declined to 9.7%, and 16.7% of recipients accepted DCD grafts. Living donation increased, accounting for 5.7% of adult and 14.6% of pediatric transplants.

In July 2023, Model for End-Stage Liver Disease (MELD) 3.0 and Pediatric End-Stage Liver Disease (PELD)-creatinine replaced MELD-sodium and PELD, respectively, alongside updated criteria for pediatric Status 1B listing. A primary objective of MELD 3.0 was to reduce sex-based disparities in access to deceased donor liver transplantation. In 2023, the male-female gap in transplant rates narrowed, although adult male candidates continued to have higher transplant rates, while adult female candidates experienced higher pretransplant mortality. Alcohol-associated liver disease and metabolic dysfunction-associated steatohepatitis remained the leading indications for liver transplantation (Organ Procurement Transplant Network (OPTN)/Scientific Registry of Transplant Recipients (SRTR), 2023).

Since 2001, the guidelines for the referral and management of patients eligible for solid organ transplantation has shifted toward multiple organ specific guidance documents and policy standards that collectively cover candidate referral, evaluation, and management. There are numerous American Society of Transplantation (AST) clinical guidelines for transplant care, reflecting evolving evidence and practice. Additionally, the National Liver Review Board (NLRB) updated guidance to liver transplant programs summarizing available transplant oncology evidence to assist clinical reviewers in approving candidates for MELD exception points. The referenced guidance is not official OPTN policy. Rather, it serves as clinical and evaluative guidance for the OPTN NLRB to support consistent review of MELD exception requests for adult liver transplant candidates with specified diagnoses. It outlines clinical considerations, disease severity indicators, and documentation elements that may be used by the NLRB when assessing whether a candidate’s risk of waitlist mortality or transplant benefit is inadequately reflected by calculated MELD scores. Specifically for the evaluation of exception case requests for adult transplant candidates with the following diagnoses (NLRB, 2025):

• Hepatocellular carcinoma
• Hepatic epithelioid hemangioendothelioma
• Hepatic adenomas
• Neuroendocrine tumors
• Colorectal liver metastases
• Intrahepatic cholangiocarcinoma

Liver Transplantation for End-Stage Organ Failure

In 2025, the American Association for the Study of Liver Diseases (AASLD) and the AST published the Practice Guideline on Adult Liver Transplantation: Candidate Evaluation, which supersedes and replaces the prior 2014 adult liver transplant guideline (Dove, 2025). The 2025 guideline emphasizes that listing decisions should be individualized, incorporating disease etiology, comorbid conditions, psychosocial assessment, frailty, and transplant benefit, rather than relying solely on laboratory-based scoring systems. The recommendations are intended to guide clinical evaluation and are not prescriptive coverage criteria. Many factors may affect the outcome of solid organ transplantation. Prior to transplantation an assessment of the individuals medical and psychosocial status must confirm that transplantation is the best treatment option for managing the individual’s disease and review of potential contraindications. The updated guidelines states that individuals with chronic liver disease are appropriate for liver transplantation consideration in:

1. Patients with chronic liver disease who experience a decompensating event should be referred for liver transplant evaluation. In the absence of a decompensating event, the MELD score threshold for referral is unclear, but data suggest that for patients on the waitlist, LT survival benefit may be achieved at MELD scores greater than 12. MELD score alone should not be a barrier to referral for transplantation. (Level of Evidence: Strong, Level 4).
2. Patients with acute-on chronic liver failure (ACLF) should be considered for referral to a liver transplant center. (Level of Evidence: Strong, Level 4)

Additionally, the guideline notes:

43. Neither high MELD score (>40) nor ACLF are contraindications to transplant. Providers should assess trajectory of clinical course, probability of an acceptable outcome, and risk of futility when deciding to move forward with transplantation. (Level of Evidence: Strong, Level 3)
44. Physical frailty/function, while a risk factor for worse outcomes after liver transplantation, should not be considered a sole contraindication to liver transplantation. (Level of Evidence: Strong, Level 2)
45. When physical frailty/function are being considered as a criterion for evaluating a patient’s transplant candidacy, we recommend use of a standardized metric to reduce subjectivity and error in this assessment. (Level of Evidence: Strong, Level 2)
46. Mental health disorders, even if serious, are not an absolute contraindication to liver transplantation. Efforts should be made to treat and stabilize mental health disorders with an opportunity for reassessment of transplant eligibility. (Level of Evidence: Strong, Level 3)
47. Yerdel grade IV PVT (complete splanchnic vein thrombosis) without sufficient collateral veins (left gastric vein, pericholedochal collaterals) is a relative contraindication to isolated liver transplantation. (Level of Evidence: Weak, Level 2)
48. Patients with BMI greater than 40 or BMI less than 18.5 should undergo muscle mass and nutritional status screening to identify treatable factors. (Level of Evidence: Strong, Level 3)
49. Patients should not be excluded from liver transplant evaluation based on BMI alone. (Level of Evidence: Strong, Level 3)

The previous 2014 AASLD and AST joint guidelines for the evaluation of adult liver transplantation recommended liver transplantation for individuals with severe acute liver failure or advanced chronic liver disease when all effective medical and non-transplant therapies had been exhausted. The guidance emphasized that formal transplant evaluation should confirm the irreversible nature of liver disease, establish that no effective alternative medical therapies are available, and determine that transplantation offers a meaningful survival or clinical benefit (AASLD, 2014).

The 2014 guidelines liver transplant indications included acute liver failure complications of cirrhosis, liver-based metabolic conditions with systemic manifestations (including α1-Antitrypsin deficiency, familial amyloidosis, glycogen storage disease, hemochromatosis, primary oxaluria, and Wilson disease) and 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.

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 (Singal, 2023). 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.

Chen (2025) reported a meta-analysis that evaluated differences in survival rates after transplantation among individuals with NASH HCC and those with non-NASH HCC. Seven studies were included; the meta-analysis revealed that there was no significant difference in overall survival between liver transplant recipients with NASH HCC and those with non-NASH HCC. The recurrence-free survival of NASH HCC recipients were longer (95% confidence interval [CI]: 0.51-0.97; p=0.03) and (95% CI: 0.72-1.07; p=0.21) for overall survival, respectively. The authors concluded that recipients with NASH HCC who undergo liver transplant have comparable overall survival rates as those with non-NASH HCC, while NASH HCC was associated with increased recurrence-free survival, however, further research in randomized trials is needed to verify the results.

The National Comprehensive Cancer Network (NCCN^®) CPG (V2.2025) 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 CPG (V2.2025) 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.

The NCCN CPG (V2.2025) for intrahepatic cholangiocarcinoma includes the following recommendations:

Patients with biopsy-proven iCCA or mixed HCC-iCCA, presence of cirrhosis, unresectable, have received locoregional or systemic therapy, and have no new lesions during the 6 months from time or diagnosis or last treatment may be eligible for MELD exception points and should be considered for transplantation.

The 2025 AASLD/AST Practice Guideline on Adult Liver Transplantation: Candidate Evaluation made a similar recommendation:

Patients with biopsy proven unresectable intrahepatic cholangiocarcinoma or mixed-hepatocellular carcinoma-cholangiocarcinoma with a maximum diameter < 3 cm, without extrahepatic disease, may be considered for liver transplantation. (Weak, Level 4) (Dove, 2025).

Additionally, in 2025 the NLRB updated guidance to liver transplant programs summarizing available evidence for MELD exception points. The updated guidance states that individuals with intrahepatic cholangiocarcinoma or mixed-hepatocellular carcinoma-cholangiocarcinoma may be considered for liver transplantation.

In the recent NCCN CPG (V3.2025) 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.

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, reaffirmed 2025).

However, the Italian Association of Medical Oncology (AIOM) in collaboration with the Italian Association for Neuroendocrine Tumors (ITANET) Clinical Practice Guideline for the Management of Non-Functioning Advanced Neuroendocrine Neoplasms (NeNs) of the Gastroenteropancreatic (GEP) Tract issued the following recommendation:

#13 In well-selected GEP-NET patients, aged <60 years, with liver metastases and liver involvement <50%, from NET to primary site drained by the portal system radically removed, with radiologically stable disease for at least 6 months, and the absolute absence of extra-hepatic disease, liver transplantation, maybe be considered after multidisciplinary discussion. Strength of recommendation: Conditional in favor.
Overall certainty of evidence: Low

Additionally, in 2025 the NLRB also updated guidance to liver transplant programs summarizing the evidence available for MELD exception points, the updated guidance states that individuals with NETs may be considered for liver transplantation under this exception.

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 (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 (Chiorean, 2022) 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 (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 (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 (IHPBA) 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 (Morris, 2022):

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 (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 NLRB “Update Related to Transplant Oncology” (2024).. 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 disease
• 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 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. Chen K, Yang M, Li G, et al. Liver transplantation for NASH-related hepatocellular carcinoma versus non-NASH etiologies of hepatocellular carcinoma: a systematic review and meta-analysis. PLoS ONE. 2025; 20(3): e0317730.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. Frenette C, Mendiratta-Lala M, Salgia R, et al. ACG Clinical Guideline: Focal Liver Lesions. Am J Gastroenterol. 2024; 119(7):1235-1271.
14. 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.
15. Haberal M, Karakayali H, Emiroğlu R, et al. Living-donor split-liver transplantation. Transplant Proc. 2001; 33(5):2726-2729.
16. Hagness M, Foss A, Line PD, et al. Liver transplantation for nonresectable liver metastases from colorectal cancer. Ann Surg. 2013; 257(5):800-806.
17. 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.
18. Heimbach JK, Haddock MG, Alberts SR, et al. Transplantation for hilar cholangiocarcinoma. Liver Transpl. 2004; 10(10 Suppl 2):S65-68.
19. 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.
20. Jophlin LL, Singal AK, Bataller R, et al. ACG Clinical Guideline: Alcohol-Associated Liver Disease. Am J Gastroenterol. 2024; 119(1):30-54.
21. Kim-Schluger L, Florman SS, Gondolesi G, et al. Liver transplantation at Mount Sinai. Clin Transpl. 2000; Chapter 21:247-253.
22. 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.
23. Mazzaferro V. Results of liver transplantation: with or without Milan criteria? Liver Transpl. 2007; 13(11 Suppl 2):S44-47.
24. Michler RE. Xenotransplantation: risks, clinical potential and future prospects. Emerg Infect Dis. 1996; 2(1):64-70.
25. 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.
26. 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.
27. 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.
28. 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.
29. Nishizaki T, Ikegami T, Hiroshige S, et al. Small graft for living donor liver transplantation. Ann Surg. 2001; 233(4):575-580.
30. 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.
31. 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.
32. 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.
33. 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.
34. 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.
35. 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.
36. Shingina A, Nizar M, Wakim-Fleming J et al. Acute liver failure guidelines. Am J Gastroenterol. 2023; 118: 1128-1153.
37. 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.
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 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. 2020; 71(1):306-333.
2. 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.  2014; 59(3):1144-1165.
3. American Society of Clinical Oncology. Management of Locally Advanced Rectal Cancer: ASCO Guideline. Updated August 8, 2024. J Clin Oncol. 2024: JCO2401160.
4. American Society of Transplant Surgeons' position paper on adult-to-adult living donor liver transplantation. Liver Transplant 2000; 6(6):815-817.
5. 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 December 30, 2025.
6. Centers for Medicare and Medicaid Services. National Coverage Determination. Available at: http://www.cms.hhs.gov/mcd/index_chapter_list.asp. Accessed on December 30, 2025.
   • Adult Liver Transplantation. NCD #260.1. Effective June 21, 2012.
   • Pediatric Liver Transplantation. NCD #260.2. Effective April 12, 1991.
7. Chiorean EG, Nandakumar G, Fadelu T,  et al. The American Society of Clinical Oncology Resource-Stratified Guideline for the Treatment of Patients With Late-Stage Colorectal Cancer. Updated October 17, 2022.  JCO Glob Oncol. 2020; 6:414-438.
8. Dove L, Chadha RM, Lai JC, DiMartini A, et al. AASLD AST Practice Guideline on adult liver transplantation: candidate evaluation. Hepatology. 2025 Dec 17. Epub ahead of print.
9. Heimbach JK, Kulik LM, Finn RS, et al. American Association for the Study of Liver Disease (AASLD). practice guidelines. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018; 67(1):358-380.
10. Morris VK, Kennedy EB, Baxter NN, et al. American Society of Clinical Oncology. Treatment of Metastatic Colorectal Cancer: ASCO Guideline. Updated October 17, 2022  J Clin Oncol. 2023; 41(3):678-700.
11. 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 December 30, 2025.
    • Biliary Tract Cancers: Version 2.2025. July 2, 2025.
    • Colon Cancer: Version 5.2025. October 30, 2025.
    • Hepatocellular Carcinoma: Version 2.2025. October 22, 2025.
    • Neuroendocrine and Adrenal Tumors Version 3.2025. October 1, 2025.
12. Organ Procurement and Transplantation Network (OPTN) and Scientific Registry of Transplant Recipients (SRTR). OPTN/SRTR 2023 Annual data report. U.S. Department of Health and Human Services, Health Resources and Services Administration; 2024. Available at: https://srtr.transplant.hrsa.gov/ADR/Chapter?name=Liver&year=2023.  Accessed on December 30, 2025.
13. Organ Procurement and Transplantation Network (OPTN). Allocation of Liver and Liver Intestines. Policy 9.5 Specific Standardized MELD or PELD Score Exceptions. Effective December 10, 2025. Available at: https://www.hrsa.gov/sites/default/files/hrsa/optn/optn_policies.pdf. Accessed on January 8, 2026.
14. Spada F, Gelsomino F, Rinzivillo M, Cinquini M, et al. Clinical practice guidelines for the management of non-functioning advanced GEP-NENs: a GRADE approach for evidence evaluation and recommendations by the Italian Association of Medical Oncology (AIOM) in collaboration with the Italian Association for Neuroendocrine Tumors (ITANET). ESMO Open. 2025 Nov; 10(11):105878.
15. Singal AG, Llovet JM, Yarchoan M, et al. American Association for the Study of Liver Disease (AASLD). Practice guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. Hepatology. 2023; 78(6):1922-1965.
16. 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.
17. Squires RH, Ng V, Romero R,  et al. 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. Hepatology. 2014 Jul;60(1):362-398.
18. United Network for Organ Sharing (UNOS). Organ Procurement and Transplantation Network. Policies: 9: allocation of livers and liver-intestines. Effective December 12, 2025. Available at: http://optn.transplant.hrsa.gov/governance/policies/. Accessed on January 26, 2026.
19. U.S. Department of Health and Human Services. Scientific Registry of Transplant Recipients (SRTR). Updated 2023. Available on: https://srtr.transplant.hrsa.gov/annual_reports/Default.aspx. Accessed on January 26, 2026.

1. American Cancer Society. Available at: https://www.cancer.org. Accessed on January 26, 2026.
2. John Hopkins Medicine. BRAF Mutation and Cancer. Available at: https://www.hopkinsmedicine.org/health/conditions-and-diseases/braf-mutation-and-cancer. Accessed on January 26, 2026.
3. Liver Review Board Guidance. Available at: The documents are available at: https://www.hrsa.gov/sites/default/files/hrsa/optn/optn_policies.pdf. Accessed on January 13, 2026.
4. National Cancer Institute. Available at: http://www.cancer.gov/cancertopics/types/alphalist. Accessed on January 26, 2026.
   • Adult primary liver cancer treatment Cancer (PDQ^®))-Health Professional Version. Updated April 17, 2025.
   • Colorectal Cancer Treatment (PDQ) Health Professional Version- Updated February 12, 2025
   • Gastrointestinal Neuroendocrine Tumors (PDQ^®)-Health Professional Version. Updated May 9, 2025.
5. 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 January 26, 2026.
6. United Network for Organ Sharing. Available at: http://www.unos.org. Accessed on January 26, 2026.

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.

No part of this publication may be reproduced, stored in a retrieval system or transmitted, in any form or by any means, electronic, mechanical, photocopying, or otherwise, without permission from the health plan.

© CPT Only – American Medical Association