Liver transplantation is currently the treatment of last resort for individuals with end-stage liver disease. Liver transplantation may be performed with a liver donation after a brain or cardiac death or with a liver segment donation from a living donor. Individuals are prioritized for transplant by mortality risk and severity of illness criteria developed by the Organ Procurement and Transplantation Network (OPTN) and the United Network of Organ Sharing (UNOS). The severity of illness is determined by the Model for End-stage Liver Disease (MELD) and Pediatric End-stage Liver Disease (PELD) scores.

A liver transplant using a cadaver or living donor may be considered medically necessary for carefully selected individuals with end-stage liver failure due to irreversibly damaged livers. Etiologies of end-stage liver disease include, but are not limited to ANY of the following;

• Hepatocellular Diseases:
  • Alcoholic liver disease; or
  • Viral hepatitis (either A, B, C, or non-A, non-B); or
  • Autoimmune hepatitis; or
  • α₁-Antitrypsin deficiency; or
  • Hemochromatosis; or
  • Nonalcoholic steatohepatitis; or
  • Protoporphyria; or
  • Wilson disease; or
• Cholestatic liver diseases:
  • Primary biliary cirrhosis; or
  • Primary sclerosing cholangitis with development of secondary biliary cirrhosis; or
  • Biliary atresia; or

• Vascular disease:
  • Budd-Chiari syndrome; or

• Primary Hepatocellular Carcinoma; or
• Inborn Errors of Metabolism; or
• Trauma and toxic reactions; or
• Miscellaneous:
  • Familial amyloid polyneuropathy.

Liver transplantation may be considered medically necessary in individuals with polycystic disease of the liver who have massive hepatomegaly causing obstruction or functional impairment.

Liver transplantation may be considered medically necessary in individuals with unresectable hilar cholangiocarcinoma.

Liver transplantation may be considered medically necessary in pediatric individuals with nonmetastatic hepatoblastoma as per UNOS and OPTN guidelines.

Liver retransplantation may be considered medically necessary in individuals with ANY of the following:

• Primary graft nonfunction; or
• Hepatic artery thrombosis; or
• Chronic rejection; or
• Ischemic type biliary lesions after donation after cardiac death; or
• Recurrent non-neoplastic disease-causing late graft failure.

Liver transplantation is experimental and investigational and therefore non-covered because the safety/and/or effectiveness of this service cannot be established by the available published peer-reviewed literature for the following situations:

• Individuals with intrahepatic cholangiocarcinoma; or
• Individuals with neuroendocrine tumors metastatic to the liver.

Liver transplantation is considered not medically necessary in ANY of the following individuals;

• Individuals with hepatocellular carcinoma that has extended beyond the liver; or
• Individuals with ongoing alcohol and/or drug abuse:
  • Note: Evidence for abstinence may vary among liver transplant programs, but generally a minimum of three (3) months is required.

Liver transplantation not meeting the criteria as indicated in this policy is considered not medically necessary.

In addition to the above criteria and subject to the discretion of the transplant center, a Hepatitis C Virus (HCV) positive donor organ may be considered medically necessary as an acceptable organ option for an HCV negative adult recipient 18 years of age or older.

Contraindications

Potential contraindications for solid organ transplant are subject to the judgment of the transplant center and may include but is not limited to the following:

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

Liver-Specific Criteria

The  MELD and PELD scores range from six (6) (less ill) to 40 (gravely ill). The MELD and PELD scores will change during an individual's tenure on the waiting list.

Individuals with liver disease related to alcohol or drug abuse must be actively involved in a substance abuse treatment program.

Tobacco consumption is a contraindication.

Individuals with polycystic disease of the liver do not develop liver failure but may require transplantation

due to the anatomic complications of a hugely enlarged liver. The MELD and PELD score may not apply to these cases. One of the following complications should be present:

• Enlargement of liver impinging on respiratory function; or
• Extremely painful enlargement of liver; or
• Enlargement of liver significantly compressing and interfering with function of other abdominal organs.

Individuals with familial amyloid polyneuropathy do not experience liver disease per se, but develop polyneuropathy and cardiac amyloidosis due to the production of a variant transthyretin molecule by the liver. MELD and PELD exception criteria and scores may apply to these cases. Candidacy for liver transplant is an individual consideration based on the morbidity of the polyneuropathy. Many individuals may not be candidates for liver transplant alone due to coexisting cardiac disease; or

Hepatocellular Carcinoma

Criteria used for individual selection of hepatocellular carcinoma (HCC) individuals eligible for liver transplant include the Milan criteria, which is considered the criterion standard, the University of California, San Francisco expanded criteria, and United Network of Organ Sharing (UNOS) criteria.

Milan Criteria

A single tumor five (5) cm or less or two (2) to three (3) tumors three (3) cm or less.

University of California, San Francisco Expanded Criteria

A single tumor 6.5 cm or less or up to three (3) tumors 4.5 cm or less, and a total tumor size of eight (8) cm or less.

UNOS Stage T2 Criteria

A single tumor two (2) cm or greater and up to five (5) cm or less or two (2) to three (3) tumors one (1) cm or greater and up to three (3) cm or less and without extrahepatic spread or macrovascular invasion.

Individuals with HCC are appropriate candidates for liver transplant only if the disease remains confined to the liver. Therefore, the individual should be periodically monitored while on the waiting list, and if metastatic disease develops, the individual should be removed from the transplant waiting list. Also, at the time of transplant, a backup candidate should be scheduled. If locally extensive or metastatic cancer is discovered at the time of exploration before hepatectomy, the transplant should be aborted, and the backup candidate scheduled for transplant.

Note that liver transplant for those with T3 HCC is not prohibited by UNOS guidelines, but such individuals do not receive any priority on the waiting list. All individuals with HCC awaiting transplant are reassessed at three (3) month intervals. Those whose tumors have progressed and are no longer stage T2 will lose the additional allocation points.

Additionally, nodules identified through imaging of cirrhotic livers are given a class five (5) designation. Class 5B and 5T nodules are eligible for automatic priority. Class 5B criteria consist of a single nodule two (2) cm or larger and up to five (5) cm (T2 stage) that meets specified imaging criteria. Class 5T nodules have undergone subsequent locoregional treatment after being automatically approved on initial application or extension. A single class 5A nodule (greater than one (1) cm and less than two (2) cm) corresponds to T1 HCC and does not qualify for automatic priority. However, combinations of class 5A nodules are eligible for automatic priority if they meet stage T2 criteria. Class 5X lesions are outside of stage T2 and ineligible for automatic exception points. Nodules less than one (1) cm are considered indeterminate and are not considered for additional priority. Therefore, the UNOS allocation system. provides strong incentives to use locoregional therapies to downsize tumors to T2 status and to prevent progression while on the waiting list.

Cholangiocarcinoma

According to the Organ Procurement and Transplant Network policy on liver allocation, candidates with cholangiocarcinoma meeting the following criteria will be eligible for a MELD or PELD exception with a 10% mortality equivalent increase every three (3) months:

• Centers must submit a written protocol for individual care to the OPTN and UNOS Liver and Intestinal Organ Transplant Committee before requesting a MELD score exception for a candidate with cholangiocarcinoma. This protocol should include selection criteria, administration of neoadjuvant therapy before transplant, and operative staging to exclude individuals with regional hepatic lymph node metastases, intrahepatic metastases, and/or extrahepatic disease. The protocol should include data collection as deemed necessary by the OPTN and UNOS Liver and Intestinal Organ Transplant Committee; or
• Candidates must satisfy diagnostic criteria for hilar cholangiocarcinoma: malignant-appearing stricture on cholangiography and one of the following: carbohydrate antigen 19-9 100 U/mL, or and biopsy or cytology results demonstrating malignancy, or aneuploidy. The tumor should be considered unresectable on the basis of technical considerations or underlying liver disease (eg, primary sclerosing cholangitis); or
• If cross-sectional imaging studies (computed tomography scan, ultrasound, magnetic resonance imaging) demonstrate a mass, the mass should be three (3) cm or less; or
• Intra- and extrahepatic metastases should be excluded by cross-sectional imaging studies of the chest and abdomen at the time of initial exception and every three (3) months before score increases; or
• Regional hepatic lymph node involvement and peritoneal metastases should be assessed by operative staging after completion of neoadjuvant therapy and before liver transplant. Endoscopic ultrasound-guided aspiration of regional hepatic lymph nodes may be advisable to exclude individuals with obvious metastases before neoadjuvant therapy is initiated; or
• Transperitoneal aspiration or biopsy of the primary tumor (either by endoscopic ultrasound, operative, or percutaneous approaches) should be avoided because of the high risk of tumor seeding associated with these procedures.

Living Donor Criteria

Donor morbidity and mortality are prime concerns in donors undergoing right lobe, left lobe, or left lateral segment donor partial hepatectomy as part of living donor liver transplant. Partial hepatectomy is a technically demanding surgery, the success of which may be related to the availability of an experienced surgical team. The American Society of Transplant Surgeons proposed the following guidelines for living donors (American Society of Transplant Surgeons: Ethics Committee. American Society of Transplant Surgeons' position paper on adult-to-adult living donor liver transplant;

• They should be healthy individuals who are carefully evaluated and approved by a multidisciplinary team including hepatologists and surgeons to assure that they can tolerate the procedure; or
• They should undergo evaluation to ensure that they fully understand the procedure and associated risks; or
• They should be of legal age and have sufficient intellectual ability to understand the procedures and give informed consent; or
• They should be emotionally related to the recipients; or
• They must be excluded if the donor is felt or known to be coerced; or
• They need to have the ability and willingness to comply with long-term follow-up.