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Liver Transplant and Combined Liver-Kidney Transplant

Policy Number: MP-489

Latest Review Date: September 2024

Category: Surgical                                                                 

POLICY:

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, the following.

A. Hepatocellular diseases

  • Alcoholic liver disease
  • Viral hepatitis (either A, B, C, or non-A, non-B)
  • Autoimmune hepatitis
  • α1-Antitrypsin deficiency
  • Hemochromatosis
  • Nonalcoholic steatohepatitis
  • Protoporphyria
  • Wilson disease.

B. Cholestatic liver diseases

  • Primary biliary cirrhosis
  • Primary sclerosing cholangitis with development of secondary biliary cirrhosis
  • Biliary atresia.

C. Vascular disease

  • Budd-Chiari syndrome.

D. Primary hepatocellular carcinoma (see Policy Guidelines section for patient selection criteria)

E. Inborn errors of metabolism

F. Trauma and toxic reactions

G. 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 (see Policy Guidelines section for individual selection criteria).

Liver transplantation may be considered medically necessary in pediatric individuals with nonmetastatic hepatoblastoma.

Liver retransplantation may be considered medically necessary in individuals with:

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

Combined liver-kidney transplantation may be considered medically necessary in individuals who qualify for liver transplantation and have advanced irreversible kidney disease.

Liver transplantation is investigational in the following situations:

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

Liver transplantation is considered investigational in the following individuals:

  • Individuals with ongoing alcohol and/or drug abuse. (Evidence for abstinence may vary among liver transplant programs, but generally a minimum of 3 months is required.)
  • Individuals with hepatocellular carcinoma that has extended beyond the liver (see Policy Guidelines section for individual selection criteria).

Extracorporeal liver assist systems are considered investigational.

POLICY GUIDELINES:

Contraindications

Potential contraindications for solid organ transplant are subject to the judgment of the transplant center and include the following:

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

Liver-Specific Criteria

The Model for End-stage Liver Disease (MELD) and Pediatric End-stage Liver Disease (PELD) scores range from 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
  • Extremely painful enlargement of liver
  • 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.

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 5 cm or less or 2 to 3 tumors 3 cm or less.

University of California, San Francisco Expanded Criteria

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

United Network for Organ Sharing Stage T2 Criteria

A single tumor 2 cm or greater and up to 5 cm or less or 2 to 3 tumors 1 cm or greater and up to 3 cm or less and without extrahepatic spread or macrovascular invasion. UNOS criteria were updated in 2022.

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. In addition, 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 transplantation 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 transplantation are reassessed at 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 5 designation. Class 5B and 5T nodules are eligible for automatic priority. Class 5B criteria consist of a single nodule 2 cm or larger and up to 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 (>1 cm and <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 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 Transplantation Network (OPTN) 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 3 months:

  • Centers must submit a written protocol for individual care to the OPTN and UNOS Liver and Intestinal Organ Transplantation Committee before requesting a MELD score exception for a candidate with cholangiocarcinoma. This protocol should include selection criteria, administration of neoadjuvant therapy before transplantation, 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 Transplantation Committee.
  • 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 biopsy or cytology results demonstrating malignancy, or aneuploidy. The tumor should be considered unresectable based on technical considerations or underlying liver disease (e.g., primary sclerosing cholangitis).
  • If cross-sectional imaging studies (computed tomography scan, ultrasound, and magnetic resonance imaging) demonstrate a mass, the mass should be less than 3 cm.
  • 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 3 months before score increases.
  • Operative staging should assess regional hepatic lymph node involvement and peritoneal metastases after completion of neoadjuvant therapy and before liver transplantation. Endoscopic ultrasound-guided aspiration of regional hepatic lymph nodes may be advisable to exclude individuals with obvious metastases before neoadjuvant therapy is initiated.
  • 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 transplantation. 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 transplantation. Liver Transplant. 2000; 6(6):815-817:

  • 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
  • They should undergo evaluation to ensure that they fully understand the procedure and associated risks
  • They should be of legal age and have sufficient intellectual ability to understand the procedures and give informed consent
  • They should be emotionally related to the recipients
  • They must be excluded if the donor is felt or known to be coerced
  • They need to have the ability and willingness to comply with long-term follow-up.

Refer to medical policy- #437 Kidney Transplant

DESCRIPTION OF PROCEDURE OR SERVICE:

Solid organ transplantation offers a treatment option for individuals with different types of end stage organ failure that can be lifesaving or provide significant improvements to an individual's quality of life. Many advances have been made in the last several decades to reduce perioperative complications. Available data supports improvement in long-term survival as well as improved quality of life particularly for liver, kidney, pancreas, heart, and lung transplants. Allograft rejection remains a key early and late complication risk for any organ transplantation. Transplant recipients require life-long immunosuppression to prevent rejection. Individuals are prioritized for transplant by mortality risk and severity of illness criteria developed by Organ Procurement and Transplantation Network and United Network of Organ Sharing.

Liver Transplantation

Liver transplantation is routinely performed as a treatment of last resort for individuals with end-stage liver disease. Liver transplantation may be performed with liver donation after a brain or cardiac death or with a liver segment donation from a living donor. Certain populations are prioritized as Status 1A (e.g., acute liver failure with a life expectancy of fewer than seven days without a liver transplant) or Status 1B (pediatric individuals with chronic liver disease). Following Status 1, donor livers are prioritized to those with the highest scores on the Model for End-stage Liver Disease (MELD) and Pediatric End-stage Liver Disease (PELD) scales. Due to the scarcity of donor livers, a variety of strategies has been developed to expand the donor pool. For example, a split graft refers to dividing a donor liver into two segments that can be used for two recipients. Living donor liver transplantation (LDLT) is now commonly performed for adults and children from a related or unrelated donor. Depending on the graft size needed for the recipient, either the right lobe, left lobe, or the left lateral segment can be used for LDLT. In addition to addressing the problem of donor organ scarcity, LDLT allows the procedure to be scheduled electively before the recipient's condition deteriorates or serious complications develop. LDLT also shortens the preservation time for the donor liver and decreases disease transmission from donor to recipient.

Combined Liver-Kidney Transplantation (CKLT)

Kidney injury is a common complication following liver transplantation and is associated with increased morbidity and mortality in transplant recipients. For individuals with both liver and kidney failure, combined liver-kidney transplantation (CKLT) could result in a modest improvement in individuals survival compared with liver transplantation alone. Since the introduction of the model for end-stage, liver disease (MELD) for the allocation of organs for liver transplantation in 2002, the heavy weighting of serum creatinine in the MELD score has significantly increased the incidence of renal dysfunction seen among individuals undergoing liver transplantation. As a result, the frequency of combined liver-kidney transplantation (CKLT) compared to liver transplantation alone has also increased. In 2014, combined liver-kidney transplantation accounted for 8.2 % of all liver transplants performed in the United States and remains to be the ideal treatment option for individuals with decompensated cirrhosis and advanced irreversible renal disease.

KEY POINTS:

The most recent literature update was performed through July 9, 2024.

Summary of Evidence

For individuals who have hepatocellular disease who receive liver transplant, the evidence includes registry studies, and systematic reviews. Relevant outcomes include overall survival (OS), morbid events, and treatment-related morbidity and mortality. Studies on liver transplantation for viral hepatitis have found that survival is lower than for other liver diseases. Although these statistics raise questions about the most appropriate use of a scarce resource (donor livers), the long-term survival rates are significant in a group of individuals who have no other treatment options. Also, survival can be improved by eradication of hepatitis virus before transplantation. For individuals with nonalcoholic steatohepatitis, OS rates have been shown to be similar to other indications for liver transplantation. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have primary hepatocellular carcinoma who receive liver transplant, the evidence includes systematic reviews of observational studies. Relevant outcomes include OS, morbid events, and treatment-related morbidity and mortality. In the past, long-term outcomes in individuals with primary hepatocellular malignancies had been poor (19%) compared with the OS of liver transplant recipients. However, recent use of standardized individual selection criteria (e.g., the Milan criteria diameter) has dramatically improved OS rates. In appropriately selected individuals, liver transplant has been shown to result in higher survival rates than resection. In individuals who present with unresectable organ-confined disease, transplant represents the only curative approach. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have extrahepatic cholangiocarcinoma who receive liver transplant, the evidence includes a systematic review of observational studies and individual registry. Relevant outcomes include OS, morbid events, and treatment-related morbidity and mortality. For individuals with extrahepatic (hilar or perihilar) cholangiocarcinoma who are treated with adjuvant chemotherapy, survival rates have been reported as high as 76%. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have intrahepatic cholangiocarcinoma who receive liver transplant, the evidence includes registry studies and a systematic review of observational studies. Relevant outcomes include OS, morbid events, and treatment-related morbidity and mortality. In a registry study comparing outcomes in individuals with intrahepatic cholangiocarcinoma who received liver transplantation to those who received surgical resection of the liver, no differences were found in OS, length of stay, or unplanned 30-day readmission rates between groups. Additional studies reporting survival rates in individuals with intrahepatic cholangiocarcinoma or in mixed populations of individuals with extrahepatic and intrahepatic cholangiocarcinoma have reported 5-year survival rates of less than 30%. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have metastatic neuroendocrine tumors who receive liver transplant, the evidence includes systematic reviews of case series. Relevant outcomes include OS, morbid events, and treatment-related morbidity and mortality. In select individuals with nonresectable, hormonally active liver metastases refractory to medical therapy, liver transplantation has been considered as an option to extend survival and minimize endocrine symptoms. While there may be centers that perform liver transplants on select individuals with neuroendocrine tumors, the available studies are limited by their heterogeneous populations. Further studies are needed to determine appropriate selection criteria. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have pediatric hepatoblastoma who receive liver transplant, the evidence includes case series. Relevant outcomes include OS, morbid events, and treatment-related morbidity and mortality. The literature on liver transplantation for pediatric hepatoblastoma is limited, but case series have demonstrated good outcomes and high rates of long-term survival. Additionally, non-metastatic pediatric hepatoblastoma is included in UNOS criteria for individuals eligible for liver transplantation. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have a failed liver transplant who receive liver retransplant, the evidence includes observational studies. Relevant outcomes include OS, morbid events, and treatment-related morbidity and mortality. Case series have demonstrated favorable outcomes with liver retransplantation in certain populations, such as when criteria for an original liver transplantation are met for retransplantation. While some evidence has suggested outcomes after retransplantation may be less favorable than for initial transplantation in some individuals, long-term survival benefits have been demonstrated. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals with indications for liver and kidney transplant who receive combined liver-kidney transplant, the evidence includes a systematic review of retrospective observational studies in adults and several individual registry studies. Relevant outcomes include OS, morbid events, and treatment-related morbidity and mortality. Most of the evidence involves adults with cirrhosis and kidney failure. Indications for combined liver-kidney transplant in children are rare and often congenital and include liver-based metabolic abnormalities affecting the kidney, along with structural diseases affecting both the liver and kidney. In both adults and children, comparisons with either liver or kidney transplantation alone would suggest that combined liver-kidney transplant is no worse, and possibly better, for graft and individual survival. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

Practice Guidelines and Position Statements

International Consensus Conference

In 2010, an International Consensus Conference, including representation from the U.S., convened with the goal of reviewing current practice regarding liver transplantation in individuals with hepatocellular carcinoma (HCC). The Conference ultimately came up with recommendations beginning from the assessment of candidates with HCC for liver transplantation and managing individuals on waitlists, to the role of liver transplantation and post-transplant management. Some notable recommendations are described.

The Milan criteria were recommended for use as the benchmark for individual selection, although it was suggested that the Milan criteria might be modestly expanded based on data from expansion studies that demonstrated outcomes are comparable with outcomes from studies using the Milan criteria. Candidates for liver transplantation should also have a predicted survival of 5 years or more. The consensus criteria indicate alpha-fetoprotein concentrations may be used with imaging to assist in determining individual prognosis.

Regarding liver retransplantation, the consensus criteria issued a weak recommendation indicating retransplantation after graft failure of a living donor transplant for HCC in individuals meeting regional criteria for a deceased donor liver transplant. A strong recommendation was issued against liver retransplantation with a deceased donor for graft failure for individuals exceeding regional criteria.  Also, the consensus criteria issued a strong recommendation that liver retransplantation for recurrent HCC would not be appropriate. However, a de novo HCC may be treated as a new tumor, and retransplantation may be considered even though data to support this are limited.

American Association for the Study of Liver Diseases and American Society of Transplantation

In 2013, the American Association for the Study of Liver Diseases (AASLD) and the American Society of Transplantation (AST) issued guidelines on evaluating individuals for liver transplant. These guidelines indicated liver transplantation for severe acute or advanced chronic liver disease after all effective medical treatments have been attempted. The formal evaluation should confirm the irreversible nature of the liver disease and lack of effective alternative medical therapy.

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

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

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

  • “Tobacco consumption should be prohibited in LT [liver transplant] candidates.”
  • “Patients with HIV [Human Immunodeficiency Virus] infection are candidates for LT if immune function is adequate and the virus is expected to be undetectable by the time of LT.”
  • “LT candidates with HCV [hepatitis C virus] have the same indications for LT as for other etiologies of cirrhosis.”

Contraindications to liver transplant included:

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

In 2014, the AASLD, AST, and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition issued joint guidelines on the evaluation of the pediatric inidivuals for liver transplant. The guidelines stated that “disease categories suitable for referral to a pediatric LT program are similar to adults: acute liver failure, autoimmune, cholestasis, metabolic or genetic, oncologic, vascular, and infectious. However, specific etiologies and outcomes differ widely from adult individuals, justifying independent pediatric guidelines.” The indications listed for liver transplantation included biliary atresia, Alagille syndrome, pediatric acute liver failure, hepatic tumors, hepatocellular carcinoma, hemangioendothelioma, cystic fibrosis−associated liver disease, urea cycle disorders, immune-mediated liver disease, along with other metabolic or genetic disorders.

In 2019, the 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 addiction to alcohol is a primary driver in selecting appropriate candidates for liver transplantation. Clinical characteristics that should trigger an evaluation and consideration for liver transplant include decompensated alcohol-associated cirrhosis, Child-Pugh-Turcotte class C cirrhosis, or a MELD-Na score ≥21. Additionally, the guideline notes 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- or lesser-risk strata for relapse.

In 2023, the AASLD released a practice guideline on the management of hepatocellular carcinoma. Evidence recommendations by the expert panel are rated based on the Oxford Center for Evidence-Based Medicine and the strength of recommendations are categorized based on the level of evidence, risk–benefit ratio, and individual preferences. Recommendations regarding liver transplantation are listed below.

"Liver transplantation should be the treatment of choice for transplant-eligible individuals with early-stage HCC occurring in the setting of clinically significant portal hypertension and/or decompensated cirrhosis (Level 2, Strong Recommendation)

AASLD advises the use of pre-transplant locoregional bridging therapy for individuals 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)

AASLD advises individuals with decompensated cirrhosis who develop T1 HCC and are eligible for LT be monitored with cross-sectional imaging at least every 3 months until criteria are met for MELD exception before pursuing LRT [locoregional therapy] (Level 3, Weak Recommendation)

Individuals who are otherwise transplant-eligible except with initial tumor burden exceeding the Milan criteria, especially those meeting United Network of Organ Sharing (UNOS) down staging criteria, should be considered for LT following successful down staging to within Milan criteria after a 3-to-6-month period of observation (Level 2, Strong Recommendation)

AASLD advised surveillance for detection of post-transplant HCC recurrence using multiphasic contrast-enhanced abdominal CT [computed tomography] or MRI [magnetic resonance imaging] and chest CT scan (Level 2, Strong Recommendation)"

National Comprehensive Cancer Network

National Comprehensive Cancer Network (NCCN) guidelines on hepatocellular carcinoma (v.2.2024) recommends referral to a liver transplant center or bridge therapy for individuals with HCC meeting UNOS criteria of a single tumor measuring 2 to 5 cm, or 2 to 3 tumors 1 to 3 cm in diameter with no macrovascular involvement or extrahepatic disease. In individuals who are ineligible for transplant and in select individuals with Child-Pugh class A or B liver function with tumors that are resectable and who fit UNOS criteria/ extended criteria, the NCCN indicates that these individuals could be considered for resection or transplant. individuals with unresectable HCC should be evaluated for liver transplantation; if the individual is a transplant candidate, then referral to a transplant center should be given or bridge therapy should be considered. The NCCN guidelines also indicate that individuals with unresectable disease who are not a transplant candidate should receive locoregional therapy with ablation, arterially directed therapies, or external beam radiation therapy or may receive systemic therapy, best supportive care, or be enrolled in a clinical trial. These are level 2A recommendations based on lower-level evidence and uniform consensus.

The NCCN guidelines on neuroendocrine tumors (v.1.2024) indicate that liver transplantation for neuroendocrine liver metastases is considered investigational despite "encouraging" 5-year survival rates.

U.S. Preventive Services Task Force Recommendations

Not applicable.

KEY WORDS:

Liver transplant, hepatic transplant, retransplantation, ELAD, HepatAssist, extracorporeal liver assist device, artificial liver, bioartificial liver, liver failure, MARS procedure, Molecular adsorbent recirculating system, living donor liver transplantation (LDLT), Orthotopic Liver Transplant (OLT), Combined liver-kidney transplant, CLKT, simultaneous liver-kidney transplantation, SLK

APPROVED BY GOVERNING BODIES:

Liver transplantation is a surgical procedure and, as such, is not subject to regulation by the U. S. Food and Drug Administration.

The U.S. Food and Drug Administration regulates human cells and tissues intended for implantation, transplantation, or infusion through the Center for Biologics Evaluation and Research, under Code of Federal Regulation title 21, parts 1270 and 1271. Liver transplants are included in these regulations.

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits. Group-specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply.

FEP: Special benefit consideration may apply. Refer to member’s benefit plan.

CURRENT CODING: 

Combined liver-kidney transplant would be reported with the codes in this policy along with the codes on kidney transplant.

CPT Codes:

47133

Donor hepatectomy (including cold preservation): from cadaver donor

47135

Liver allotransplantation; orthotopic; partial or whole, from cadaver or living donor, any age

47140

Donor hepatectomy (including cold preservation), from living donor; left lateral segment only (segments II and III)

47141

: total left lobectomy (segments II, III, and IV)

47142

: total right lobectomy (segments V, VI, VII, and VIII)

47143

Backbench standard preparation of cadaver donor whole liver graft prior to allotransplantation, including cholecystectomy, if necessary, and dissection and removal of surrounding soft tissues to prepare the vena cava, portal vein, hepatic artery, and common bile duct for implantation; without tri-segment or lobe split

47144

; with tri-segment split of whole liver graft into 2 partial liver grafts (i.e., left lateral segment [segments II and III] and right tri-segment [segments I and IIV through VIII])

47145

; with lobe split of whole liver graft into 2 partial liver grafts (i.e., Left lobe [segments II, III, and IV] and right lobe [segments I and V through VIII])

47146

Backbench reconstruction of cadaver or living donor liver graft prior to Allotransplantation; venous anastomosis, each

47147

: arterial anastomosis, each

50300

Donor nephrectomy (including cold preservation); open from cadaver, unilateral or bilateral

50320

Donor nephrectomy (including cold preservation); open, from living donor

50323

Backbench standard preparation of cadaver donor renal allograft prior to transplantation, including dissection and removal of perinephric fat, diaphragmatic and retroperitoneal attachments, excision of adrenal gland, and preparation of ureter(s), renal vein(s), and renal artery(s), ligating branches as necessary

50325

Backbench standard preparation of living donor renal allograft (open or laparoscopic) prior to transplantation, including dissection and removal of perinephric fat and preparation of ureter(s), renal vein(s), and renal artery(s), ligating branches as necessary

50327

Backbench reconstruction of cadaver or living donor renal allograft prior to transplantation; venous anastomosis, each

50328

Backbench reconstruction of cadaver or living donor renal allograft prior to transplantation; arterial anastomosis, each

50329

Backbench reconstruction of cadaver or living donor renal allograft prior to transplantation; ureteral anastomosis, each

50340

Recipient nephrectomy

50360

Renal allotransplantation, implantation of graft; without recipient nephrectomy

50365

Renal allotransplantation, implantation of graft; with recipient nephrectomy

50547

Laparoscopy, surgical; donor nephrectomy (including cold preservation) from living donor

99499

Unlisted evaluation and management service

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  20. de la Cerda F, Jimenez WA, Gjertson DW, et al. Renal graft outcome after combined liver and kidney transplantation in children: UCLA and UNOS experience. Pediatr Transplant. Jun 2010; 14(4):459-464.
  21. Fan ST, Le Treut YP, Mazzaferro V, et al. Liver transplantation for neuroendocrine tumour liver metastases. HPB (Oxford). Jan 2015; 17(1):23-28.
  22. Firl DJ, Kimura S, McVey J, et al. Reframing the approach to patients with hepatocellular carcinoma: Longitudinal assessment with hazard associated with liver transplantation for HCC (HALTHCC) improves ablate and wait strategy. Hepatology. Oct 2018; 68 (4): 1448-1458. 
  23. Fong TL, Khemichian S, Shah T, et al. Combined liver-kidney transplantation is preferable to liver transplant alone for cirrhotic patients with renal failure. Transplantation. Aug 27 2012; 94(4):411-416. 
  24. Friman S, Foss A, Isoniemi H, et al. Liver transplantation for cholangiocarcinoma: selection is essential for acceptable results. Scand J Gastroenteralgia. Mar 2011; 46(3):370-5.
  25. Gadiparthi C, Cholankeril G, Perumpail BJ, et al. Use of direct-acting antiviral agents in hepatitis C virus-infected liver transplant candidates. World J Gastroenteralgia. Jan 21 2018; 24(3): 315-322.
  26. Grant RC, Sandhu L, Dixon PR et al. Living vs. deceased donor liver transplantation for hepatocellular carcinoma: a systematic review and meta-analysis. Clin Transplant 2013; 27(1):140-147.
  27. Gu J, Bai J, Shi X et al. Efficacy and safety of liver transplantation in patients with cholangiocarcinoma: a systematic review and meta-analysis. Int J Cancer 2012; 130(9):2155-2163.
  28. Guiteau JJ, Cotton RT, Washburn WK et al. An early regional experience with expansion of Milan Criteria for liver transplant recipients. Am J Transplant 2010; 10(9):2092-2098.
  29. Hamilton EC, Balogh J, Nguyen DT, et al. Liver transplantation for primary hepatic malignancies of childhood: The UNOS experience. J Pediatr Surg. 2017.
  30. Heimbach JK, Gores GJ, Haddock MG et al. Predictors of disease recurrence following neoadjuvant chemoradiotherapy and liver transplantation for unresectable perihilar cholangiocarcinoma. Transplantation. Dec 27 2006; 82(12):1703-7.
  31. Heimbach JK. Successful liver transplantation for hilar cholangiocarcinoma. Curr Opin Gastroenteralgia 2008; 24(3):384-388.
  32. Hong JC, Kaldas FM, Kositamongkol P, et al. Predictive index for long-term survival after retransplantation of the liver in adult recipients: analysis of a 26-year experience in a single center. Ann Surg. Sep 2011;254 (3):444-448; discussion 448-449.
  33. Hue JJ, Rocha FG, Ammori JB, et al. A comparison of surgical resection and liver transplantation in the treatment of intrahepatic cholangiocarcinoma in the era of modern chemotherapy: An analysis of the National Cancer Database. J Surg Oncol. Mar 2021; 123(4): 949-956.
  34. Ioannou GN, Perkins JD, Carithers RL, Jr. Liver transplantation for hepatocellular carcinoma: impact of the MELD allocation system and predictors of survival. Gastroenterology. May 2008; 134(5):1342-1351. 
  35. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press. 
  36. Lunsford KE, Bodzin AS, Markovic D, et al. Avoiding futility in simultaneous liver-kidney transplantation: analysis of 331 consecutive patients listed for dual organ replacement. Ann Surg. May 2017; 265(5):1016-1024. 
  37. Maggs JR, Suddle AR, Aluvihare V et al. Systematic review:  the role of liver transplantation in the management of hepatocellular carcinoma. Aliment Pharmacol Ther. May 2012; 35(10):1113-1134.
  38. Malago M, Testa G, Marcos A et al. Ethical considerations and rationale of adult-to-adult living donor liver transplantation. Liver Transpl. Oct 2001; 7(10):921-927.
  39. Malek MM, Shah SR, Atri P et al. Review of outcomes of primary liver cancers in children: our institutional experience with resection and transplantation. Surgery. Oct 2010; 148(4):778-782; discussion 782-784.
  40. Marcos A, Ham JM, Fisher RA et al. Single-center analysis of the first 40 adult-to-adult living donor liver transplants using the right lobe. Liver Transpl 2000; 6(3):296-301.
  41. Mathe Z, Tagkalos E, Paul A et al. Liver transplantation for hepatic metastases of neuroendocrine pancreatic tumors: a survival-based analysis. Transplantation. Mar 15 2011; 91(5):575-582.
  42. Mazzaferro V, Regalia E, Doci R et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996; 334(11):693-699.
  43. Meyer CG, Penn I, James L. Liver transplantation for cholangiocarcinoma: results in 207 patients. Transplantation 2000; 69(8):1633-1637.
  44. Murali AR, Patil S, Phillips KT, et al. Locoregional therapy with curative intent versus primary liver transplant for hepatocellular carcinoma: systematic review and meta-analysis. Transplantation. Jan 2017 101(8): e249-e257.
  45. National Comprehensive Cancer Network. Hepatocellular Carcinoma. Version 2.2024. www.nccn.org/professionals/physician_gls/PDF/hepatobiliary.pdf. 
  46. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Hepatobiliary Cancers. Version 4.2020. www.nccn.org/professionals/physician_gls/pdf/hepatobiliary.pdf.
  47. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Neuroendocrine and Adrenal Tumors. Version 1.2024. www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdf.
  48. Organ Procurement and Transplantation Network (OPTN). Organ Distribution: Allocation of Livers. 2013. optn.transplant.hrsa.gov/PoliciesandBylaws2/policies/pdfs/policy_8.pdf.
  49. Organ Procurement and Transplantation Network. Simultaneous Liver and Kidney allocation. 2016; optn.transplant.hrsa.gov/governance/public-comment/simultaneous-liver-kidney-allocation-2016/.
  50. Organ Procurement and Transplantation Network. Simultaneous liver kidney allocation: Briefing paper. 2016; optn.transplant.hrsa.gov/media/1871/kidney_briefingpaper_slk_201606.pdf.
  51. Organ Procurement and Transplantation Network (OPTN). Policy 9: Allocation of Livers and Liver-Intestines. optn.transplant.hrsa.gov/media/1200/optn_policies.pdf#nameddest=Policy_01. 
  52. Organ Procurement and Transplantation Network (OPTN). Organ Procurement and Transplantation Network Policies. optn.transplant.hrsa.gov/media/1200/optn_policies.pdf. 
  53. Pascher A, Jonas S, Neuhaus P. Intrahepatic cholangiocarcinoma: indication for transplantation. J Hepatobiliary Pancreat Surg 2003; 10(4):282-287.
  54. Pomfret EA Washburn K, Wald C et al. Report of a national conference on liver allocation in patients with hepatocellular carcinoma. Liver Transpl 2010; 16(3):262-278.
  55. 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.
  56. Remiszewske P, Kalinowski P et al. Influence of selected factors on survival after liver retransplantation. Transplant Proc 2011; 43(8):3025-3028.
  57. Renz JF, Busuttil RW. Adult-to-adult living-donor liver transplantation: a critical analysis. Semin Liver Dis 2000; 20(4):411-424.
  58. Robles R, Figueras J, Turrion VS et al. Spanish experience in liver transplantation for hilar and peripheral cholangiocarcinoma. Ann Surg. Feb 2004; 239(2):265-271.
  59. Ruiz R, Jennings LW, Kim P, et al. Indications for combined liver and kidney transplantation: propositions after a 23-yr experience. Clin Transplant. Nov-Dec 2010; 24(6):807-811.
  60. Salimi J, Jafarian A, Fakhar N, et al. Study of re-transplantation and prognosis in liver transplant center in Iran. Gastroenterol Hepatol Bed Bench. 2021; 14(3): 237-242.
  61. Schoenberg MB, Bucher JN, Vater A, et al. Resection or transplant in early hepatocellular carcinoma. Dtsch Arztebl Int. 2017 114(31-32):519-526.
  62. Sheiner P, Rochon C. Recurrent hepatitis C after liver transplantation. Mt Siai J Med 2012; 79(2):190-198.
  63. Shiffman ML, Brown RS, Jr., Olthoff KM et al. Living donor liver transplantation: summary of a conference at The National Institutes of Health. Liver Transpl. Feb 2002; 8(2):174-188.
  64. Singal AG, Llovet JM, Yarchoan M, et al. AASLD practice guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. Hepatology. May 22 2023.
  65. Squires RH, Ng V, Romero R, et al. 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. Jul 2014; 60(1):362-398.
  66. Tang W, Qiu JG, Cai Y, et al. Increased Surgical Complications but Improved Overall Survival with Adult Living Donor Compared to Deceased Donor Liver Transplantation: A Systematic Review and Meta-Analysis. Biomed Res Int. 2020; 2020: 1320830.
  67. Terrault NA, Roland ME, Schiano T et al. Outcomes of liver transplant recipients with hepatitis C and human immunodeficiency virus coinfection. Liver Transplant. Jun 2012; 18(6):716-726.
  68. Wang X, Li J, Riaz DR, et al. Outcomes of liver transplantation for nonalcoholic steatohepatitis: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. Mar 2014; 12(3):394-402.e391.
  69. Working Party of the British Transplantation Society. Kidney and Pancreas Transplantation in Patients with HIV. Second Edition (Revised). British Transplantation Society Guidelines. Macclesfield, UK: British Transplantation Society; 2017.
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POLICY HISTORY:

Medical Policy Panel, September 2011

Medical Policy Group, October 2011 (2): New Policy

Medical Policy Administration Committee, November 2011

Available for comment November 11 through December 27, 2011

Medical Policy Panel, December 2012

Medical Policy Group, March 2013 (2): Non-alcoholic steatohepatitis cirrhosis added as covered indication; statement regarding coverage of retransplantation added.  Key Points, Key Words, References updated to support new coverage statements

Medical Policy Administration Committee, April 2013

Available for comments April 18 through June 5, 2013

Medical Policy Panel, January 2014

Medical Policy Group, January 2014 (3):  Updates to Description, Policy Statement, Key Points & References; policy statement updated to include coverage criteria related to polycystic disease of the liver who have massive hepatomegaly causing obstruction or functional impairment; pediatric patients with non-metastatic hepatoblastoma; statement that liver transplantation considered investigational in all other situations not specifically addressed elsewhere in policy section.

Medical Policy Administration Committee, February 2014

Available for comment January 23 through March 7, 2014

Medical Policy Panel, January 2015

Medical Policy Group, January 2015 (2): 2015 Updates to Description, Key Points, and References, no change to policy statement.

Medical Policy Group, November 2015: 2016 Annual Coding Update. Added CPT code 47399 to current coding. Created previous coding section and moved CPT code 47136 from current coding to previous coding.

Medical Policy Group, December 2015 (4): Added extracorporeal liver assist devices are investigational. Updates to Key Points, Key Words, Coding, and References.

Medical Policy Group, June 2017 (7): 2017 Updates to Description, Policy statement- added HIV criteria; clarified absolute contraindications and removed old criteria from 2014 and 2013.

Medical Policy Administration Committee, July 2017

Available for comment June 23 through August 6, 2017

Medical Policy Panel, September 2017

Medical Policy Group, October 2017 (7): 2017 Updates to Description, Key Points, Approved by Governing Bodies and References; Policy statement- HIV criteria updated. No change in intent.

Medical Policy Panel, August 2018

Medical Policy Group, August 2018 (3): 2018 Updates to Description, Key Points, Approved by Governing Bodies, References, and Key Words: added Living Donor Liver Transplant (LDLT) and Orthotopic Liver Transplant (OLT). No changes to policy statement or intent.

Medical Policy Panel, August 2019

Medical Policy Group, September 2019 (3): 2019 Updates to Key Points, Practice Guidelines and Position Statements and References. No changes to policy statement or intent.

Medical Policy Group, March 2020 (3): 2020 Updates to policy statement. Combined Liver-Kidney Transplant medical policy 647 with medical policy 489- Liver Transplant. Added policy guidelines section. Added Key Words from medical policy 647 - Combined Liver-Kidney Transplant: added: Combined liver-kidney transplant, CLKT, simultaneous liver-kidney transplantation, SLK. No other changes to policy statement or intent. Added references from medical policy 647 specific to combined liver-kidney transplant. Coding updated to include kidney transplantation. Title change from Liver Transplant to Liver Transplant and Combined Liver-Kidney Transplant.

Medical Policy Panel, August 2020

Medical Policy Group, September 2020 (3): 2020 Updates to Description, Key Points, Practice Guidelines and Position Statements, and References. Policy Guidelines updated with language clarification on substance abuse criteria. Language added to Policy Guidelines: “A documented plan must be in place to assure sobriety prior to and following transplantation”. No changes to policy statements or intent.

Medical Policy Administration Committee, October 2020

Medical Policy Group, November 2020 (3): 2021 Annual Coding Update. Added CPT 99499 to Current Coding. Deleted CPT code 0405T from the Current coding section. Updated Previous coding section to include code 0405T.

Medical Policy Panel, August 2021

Medical Policy Group, September 2021(3): Annual Update to Description, Key Points, Practice Guidelines and Position Statements, and References. Updated policy statement to remove “not medically necessary” where appropriate, no other changes to policy statement.

Medical Policy Panel, August 2022

Medical Policy Group, September 2022 (3): 2022 Updates to Description, Key Points, Practice Guidelines and Position Statements, and References. Removed HIV positive patient criteria from policy section to reflect standard of care guidelines from the American Society of Transplantation. Removed absolute contraindications in policy guidelines and changed verbiage to “Potential contraindications for solid organ transplant are subject to the judgment of the transplant center.” No other changes to policy statement or intent.

Medical Policy Panel, August 2023

Medical Policy Group, September 2023 (3): 2023 Updates to Description, Key Points, Practice Guidelines and Position Statements, Benefit Applications, and References. Removed Previous Coding section. No changes to policy statement or intent.

Medical Policy Panel, August 2024

Medical Policy Group, September 2024 (3): Updates to Description, Key Points, and References. No changes to policy statement or intent.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.