Liver transplantation is now routinely performed as the treatment of choice for patients with end-stage liver disease.  Donor livers are most commonly obtained from deceased donors, in which a whole or partial (split) liver may be transplanted.  Living donors are another possible source from adult to child or adult to adult.

Note: Members must meet the disease specific criteria as well as the general patient selection criteria 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 patients with end-stage organ failure due to irreversible liver damage that includes, but is not limited to, the following conditions:

1. Cholestatic liver diseases:
   • Primary biliary cirrhosis
   • Primary sclerosing cholangitis
   • Biliary atresia
   • Caroli's disease
   • Familial cholestasis
   • Arteriohepatic dysplasia (Alagaille's disease)
   • Cystic Fibrosis
2. Hepatocellular injury:
   • Viral induced - Hepatitis
   • Drug induced –
     Acetaminophen
     Associated with halothane, gold, disulfram, others
   • Alcohol induced
   • Toxin exposure: Amanita mushroom poisoning
   • Autoimmune hepatitis
3. Inborn errors of metabolism:
   • Wilson's disease
   • Organic acidurias
   • Hemochromatosis
   • Alpha-1 antitrypsin deficiency
   • Homozygous type II hyperlipoproteinemia
   • Crigler-Najjar Syndrome type I
   • Protoporphyria
   • Urea cycle deficiencies
   • Glycogen storage diseases types I and IV
   • Tyrosine deficiency
   • Citrulenmia
   • Ornithine transcarboxylase deficiency
   • Familial amyloid polyneuropathy (requires transplantation - polyneuropathy and cardiac amyloidosis development due to the production of a variant transthyretin molecule by the liver)
   • Oxalosis (primary)
4. Acute Diseases:
   • Fulminant hepatic failure
5. Mass Occupying Lesions:
   • Polycystic disease of the liver (requiring transplantation due to the anatomic complications of a hugely enlarged liver)
   • Hepatoblastoma confined to the liver
   • Hepatocellular carcinoma confined to the liver
   • Hemangioendothelioma
6. Vascular disease:
   • Budd-Chiari Syndrome
7. Other:
   • Cryptogenic cirrhosis

Liver Retransplantation

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

Retransplantation in patients with chronic rejection and/or recurrent disease is considered medically necessary when the patient meets general selection criteria as defined below.

Investigational/Not Medically Necessary:

Liver transplants in patients with extrahepatic malignancy, including, but not limited to, cholangiocarcinoma or hepatocellular carcinoma when either condition extends beyond the liver, are considered investigational/not medically necessary.

All other conditions that do not lead to end-stage organ failure due to irreversible liver damage are considered investigational/not medically necessary.

Xenotransplantation is considered investigational/not medically necessary.

Bioartificial liver devices are considered investigational/not medically necessary.

Note: In certain situations, a member may present with two or more concurrent medical conditions in which one would be considered an indication for transplantation, while another may be considered an exclusion or a comorbidity that would preclude a successful outcome as defined by the transplant center's protocol or nationally accepted standards. Such cases will be reviewed on an individual basis for coverage determination to assess the member's candidacy for transplantation and whether the member meets the transplant center's protocol.

General Patient Selection Criteria

In addition to having end stage liver disease, the patient 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 patient noncompliance, which places the organ at risk by not adhering to medical recommendations
6. Potential complications from immunosuppressive medications are unacceptable to the patient
7. AIDS (diagnosis based on CDC definition of CD4 count, 200cells/mm3) unless the following are noted:
   1. CD4 count >200cells/mm3 for >6 months
   2. HIV-1 RNA undetectable
   3. On stable anti-retroviral therapy > 3 months
   4. No other complications from AIDS (e.g., opportunistic infection, including aspergillus, tuberculosis, coccidioide-mycosis, 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.

Transplantation for progressive liver disease that will ultimately lead to a fatal outcome, or end-stage liver disease, is currently accepted as a practical and established medical therapy. Technical and pharmaceutical advances have made liver transplantation available to patients who might not have previously qualified, such as those diagnosed with hepatitis or hepatocellular carcinoma.  The question is no longer whether to perform this complex surgery but how to identify the best candidates. Multiple clinical trials have been conducted on various aspects of liver transplantation including, but not limited to surgical technique, immunosuppressive therapy, diagnosis, and the United Network for Organ Sharing (UNOS) status at the time of transplant. The best available evidence, collected from retrospective registry data on liver transplantation in the U.S., is based on UNOS data collected from 1985-1999 which reports one and ten year survival data. Liver transplant using a deceased or living donor is considered medically necessary for selected patients with end-stage organ failure due to irreversible liver damage.

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/not medically necessary.

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 patients 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.

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 patient).  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 patient receives the left lobe and an adult patient receives the right lobe.

Living-related donor transplantation of the left lateral segment primarily benefits pediatric patients 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 United Network for Organ Sharing (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 (Model for End-stage Liver Disease and Pediatric End-stage Liver Disease). A national database of transplant candidates, donors, recipients, and donor-recipient matching and histocompatibility is maintained by UNOS.

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.

Cadaver or deceased: the physical remains of a deceased person

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

Heterotopic: grafted or transplanted into an abnormal position

In situ: in the natural or original position

MELD: Model for End-Stage Liver Disease

Orthotopic: of or relating to the grafting of tissue in a natural position

PELD: pediatric end-stage liver disease

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 policy 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:

CPT

ICD-9 Procedure

Revenue codes

When services are Investigational/Not Medically Necessary:

For the procedure codes listed above, when criteria are not met; or when the code describes a procedure indicated in the Policy section as investigational/not medically necessary.

When services are also Investigational/Not Medically Necessary:

ICD-9 Procedure

ICD-9 Diagnosis

Peer Reviewed Publications:

1. Abecassis M, Adams M, 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?  Transpl. 2001; 71:1498-1499.
3. Allen JW, Hassanein T, Bhatia SN. Advances in bioartificial liver devices. hepatology 2001; 34(3): 447-455.
4. Chamuleau RA. Bioartificial liver support. Metab Brain Dis 2002; 17(4): 485-491.
5. Charlotte F, et al. Vascular lesions of the liver in sickle cell disease: a clinicopathological study in 26 living patients. Archives of Pathology and Laboratory Medicine. 1995;119:46-52. 
6. Ding YT, Qiu YD 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.
7. Dumortier J,  Czyglik O,  Poncet G, et al.  Eversion thrombectomy for portal vein thrombosis during liver transplantation. Am Journal Transplantation.  2002; 2(10):934-8.
8. Efrati O, Barak A, A Modan-Moses D, et al. Liver cirrhosis and portal hypertension in cystic fibrosis. Eur J Gastroenterol Hepatol. 2003; 15(10):1073-8. 
9. Emre S, et al. Liver transplantation in a patient with acute liver failure due to sickle cell intrahepatic cholestasis. Transplantation. 2000;69:675-6.
10. 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. 2000.
11. Haberal M, Karakayali H, et al.  Living-donor split-liver transplantation.  Transpl Proceedings. 2001; 33:2726-2729.
12. Heimbach JK, Haddock MG, Alberts SR, et al. Transplantation for hilar cholangiocarcinoma. Liver Transpl. 2004 Oct;10(10 Suppl 2):S65-8.
13. Huan KW, Choa A, et al. Hepatic encephalopathy and cerebral blood flow improved by liver dialysis. Int J Artif Organs 2003; 26(2): 149-151.
14. Kim-Schluger L, Florman SS, et al.  Liver transplantation at Mount Sinai.  Clin Transpl 2000; Chapter 21:247-253.
15. Lim KJ, Keeffe EB. Liver transplantation for alcoholic liver disease: current concepts and length of sobriety. Liver Transplantation. 2004;10(10 Suppl 2):S31-38. 
16. Michler RE. Xenotransplantation: risks, clinical potential and future prospects. Emerging Infectious Diseases 1996; 2(1): 64-69.
17. Molmenti E, Roodhouse T,  Molmenti H, et al. Thrombendvenectomy for organized portal vein thrombosis at the time of liver transplantation.  advances in surgical technique.  Annals of Surgery. 235(2):292-296.
18. 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. 
19. 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 Aug;35(5):1863-5. 
20. Nair S, et al. Obesity and its effect on survival in patients undergoing orthotopic liver transplantation in the US. Hepatology. 2002;35:105-9.
21. Nishizaki T, Ikegami T, et al.  Small graft for living donor liver transplantation.  Ann Surg 2001; 233(4):575-580.
22. Pomfret EA, Pomposelli JJ, et al.  Live donor adult liver transplantation using right lobe grafts.  Arch Surg 2001; 136:425-433.
23. Rea DJ, Heimbach JK, Rosen CB, et al. Liver transplantation with neoadjuvant chemoradiation is more effective than resection for hilar cholangiocarcinoma. Ann Surg. 2005 Sep;242(3):451-8; discussion 458-61.
24. Sakamoto S, Uemoto S, et al.  Graft size assessment and analysis of donors for living donor liver transplantation using right lobe.  Transpl 2001; 71(10):1407-1413.
25. Sans M, Rimola A, Navasa M, et al. Liver transplantation in patients with Caroli's disease and recurrent cholangitis. Transplant Int. 1997;10:241-44. 
26. 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.
27. Steinman TI, Becker BN, Frost AE, et al.  Guidelines for the referral and management of patients eligible for solid organ transplantation.  Transplantation. 2001; 71:1189-1204.
28. Sugawara Y, Masatoshi M, et al.  Small-for-size grafts in living-related liver transplantation. J Am Coll Surg.2001; 192(4):510-513.  

Government Agency, Medical Society, and Other Authoritative Publications:

1. Agency for Health Care Policy and Research. Assessment of Liver Transplantation 1990. Available at:    http://www.ahrq.gov/clinic/liver2.htm. Accessed October 8, 2006. 
2. American Association for the Study of Liver Diseases (AASLD). Practice Guidelines: Evaluation of the Patient for Liver Transplantation. Available at:    https://www.aasld.org/eweb/docs/practiceguidelines/ evalu_patient_livertransplantation.pdf. Accessed October 9, 2006.
3. American Society of Transplant Surgeons' position paper on adult-to-adult living donor liver transplantation. Liver Transplant 2000; 6(6):815-7.
4. Centers for Medicare and Medicaid Services. National Coverage Determination for Adult Liver Transplantation. NCD #260.1. Effective September 1, 2001.  http://www.cms.hhs.gov/mcd/index_chapter_list.asp. Accessed on October 8, 2006.
5. Centers for Medicare and Medicaid Services. National Coverage Determination for Pediatric Liver Transplantation. NCD #260.2. Effective April 21, 1991.  http://www.cms.hhs.gov/mcd/index_chapter_list.asp. Accessed on October 8, 2006.
6. Department of Health and Human Services. Guidelines for xenotransplantation safety. Available at:    http://www.hhs.gov/news/press/2000pres/20000526.html. Accessed October 8, 2006.
7. Hayes Inc. Hayes Medical Technology Directory. Liver Transplantation, Adult. Lansdale, PA:  Hayes, Inc.; July 2002. Search updated July 3, 2006.
8. Hayes Inc. Hayes Medical Technology Directory. Liver Transplantation, Pediatric. Lansdale, PA:  Hayes, Inc.; July 2002. Search updated July 11, 2006. .

1. TransWeb: All about transplantation and donation: http://www.transweb.org Accessed October 8, 2006.
2. United Network for Organ Sharing: http://www.unos.org Accessed October 8, 2006.

Bioartificial Liver Device (BAL)

Liver Transplant: Orthotopic and Heterotopic

LIVERx 200Ô Bioartificial Liver System

SybiolÒ 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