BlueCross and BlueShield of Montana Medical Policy/Codes
Liver Transplant
Chapter: Transplant
Current Effective Date: October 25, 2013
Original Effective Date: July 09, 2008
Publish Date: October 25, 2013
Revised Dates: March 1, 2010; January 18, 2012; September 25, 2013
Description

Recipients

Liver transplantation is now routinely performed as a treatment of last resort for patients with end-stage liver disease.  Prioritization for transplant is based on length of time on the waiting list and severity of illness.  The priority classification was developed by the United Network of Organ Sharing (UNOS).  Since February 2002, UNOS eliminated the original liver classification system, which was based on assignment to Status 1, 2A, 2B, or 3. 

The new classification retains the Status 1, which describes patients with acute liver failure with a life expectancy of less than seven days, and Status 7, which describes patients who are temporarily inactive due to intercurrent medical problems.  Status 2A through 3 are replaced with a new scoring system: model for end-stage liver disease (MELD) and pediatric end-stage liver disease (PELD) for patients under age 18 years.  Status 2A, 2B, and 3 were based on the Child-Turcotte-Pugh score, which included a subjective assessment of symptoms as part of the scoring system.  MELD and PELD are a continuous disease severity scale based on objective laboratory values.  These scales have been found to be highly predictive of the risk of dying from liver disease for patients on a transplant list.  The MELD score incorporates bilirubin, prothrombin time (i.e., international normalized ratio [INR]), and creatinine into an equation, producing a number that ranges from 1 to 40.  The PELD score incorporates albumin, bilirubin, INR growth failure, and age at listing.  Aside from the Status 1, donor livers are prioritized to those with the highest MELD or PELD score.  Waiting time will only be used to break ties among patients with same MELD or PELD score and blood type compatibility.  With the old classification system, waiting time was often a determinant of liver allocation.  However, waiting time was found to be a poor predictor of the urgency of liver transplant, since some patients were listed early in the course of their disease, while others were listed only when they became sicker.  In the new MELD or PELD allocation system, patients with higher MELD or PELD scores will always be considered before those with lower scores, even if some patients with lower scores have waited longer.

Donors

Due to the scarcity of donor livers, a variety of strategies have been developed to expand the donor pool.  For example, split graft refers to dividing a donor liver into two segments that can be used for two recipients.  Living-donor transplantation of the left lateral segment is now commonly performed between parent and child.  Recently, adult-to-adult living-donor transplantation has been investigated, using the right lobe of the liver from a related or unrelated donor.  In addition to addressing the problem of donor organ scarcity, 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 pretransplant.

General

The MELD and PELD scores range from 6 (less ill) to 40 (gravely ill).  The MELD and PELD scores will change during the course of a patient's tenure on the waiting list.

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

Patients 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 or 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.

Patients 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.  The MELD or PELD score may apply to these cases.  Candidacy for liver transplant is an individual consideration based on the morbidity of the polyneuropathy.  Many patients may not be candidates for liver transplant alone due to coexisting cardiac disease.

Patients with HCC are appropriate candidates for liver transplant only if the disease remains confined to the liver.  Therefore, the patient should be periodically monitored while on the waiting list, and if metastatic disease develops, the patient 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 prior to hepatectomy, the transplant should be aborted, and the backup candidate scheduled for transplant.

Policy

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions.  Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply.  If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

 Coverage

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

  • Hepatocellular diseases:
    1. Alcoholic cirrhosis;
    2. Cryptogenic cirrhosis;
    3. Viral hepatitis (types A, B, C, Non A, or Non B);
    4. Auto-Immune hepatitis;
    5. Alpha-1 antitrypsin deficiency;
    6. Hemochromatosis;
    7. Protoporphyria;
    8. Wilson's disease;
  • Cholestatic liver diseases:
    1. Primary biliary cirrhosis;
    2. Primary sclerosing cholangitis (PSC) with development of secondary biliary cirrhosis;
    3. Biliary atresia;
  • Vascular disease (Budd-Chiari syndrome);
  • Primary hepatocellular carcinoma (HCC);
  • Inborn errors of metabolism;
  • Trauma and toxic reactions;
  • Miscellaneous:
    1. Polycystic disease of the liver; 
    2. Familial amyloid polyneuropathy.

Liver transplant may be considered medically necessary for patients with early stage cholangiocarcinoma (CCA) that is unresectable or arising in the setting of underlying PSC, when:

  • Mayo protocol is/will be followed; and
  • UNOS  (United Network of Organ Sharing) criteria for transplant with CCA diagnosis have been met.

Liver transplant is considered experimental, investigational and unproven in patients with:

  • Extrahepatic malignancy (other than CCA, as outlined above);
  • HCC extending beyond the liver;
  • Ongoing alcohol and/or drug abuse. Note: Evidence for abstinence may vary among liver transplant programs, but generally a minimum of three months is required.

Rationale

As experience with liver transplant has matured, patient selection criteria have broadened to include a wide variety of etiologies.  The most controversial etiologies include viral hepatitis and primary hepatocellular cancer.  In particular, the presence of hepatitis B virus (HBV) has been a controversial indication for liver transplantation because of the high potential for recurrence of the virus and subsequent recurrence of liver disease.  However, registry data indicate a long-term survival rate (seven years) of 47% in HBV positive (HBV+) transplant recipients, which is lower than that seen in other primary liver diseases such as primary biliary cirrhosis (71%) or alcoholic liver disease (57%).  Although these statistics raise questions about the most appropriate use of a scarce resource (donor livers), the long-term survival rate of 45% is significant in a group of patients who have no other treatment options.  Similarly, the long-term outcome in patients with primary hepatocellular malignancies (19%) is poor compared to the overall survival of liver transplant recipients.  Nevertheless, transplant represents the only curative approach for many of these patients who present with unresectable organ-confined disease.  However, liver transplant cannot be considered curative in patients with locally extensive or metastatic liver cancer, or in patients with isolated liver metastases with extrahepatic primaries or in cholangiocarcinoma (CCA).

Due to the scarcity of donor organs and the success of living donation between parent and child, adult-to-adult living-donor liver transplantation has been investigated and is now performed at several transplant centers.   Specifically, the living donor undergoes hepatectomy of the right lobe, which is then transplanted into the recipient.  Since right hepatectomy involves the resection of 60%-70% of the total volume of the donor liver, the safety of the donor has been the major concern.  For example, the surgical literature suggests that right hepatectomy of a diseased or injured liver is associated with mortality rates of about 5%.  However, initial reports suggest that right hepatectomy in healthy donors has a lower morbidity and mortality.  The Medical College of Virginia appears to have the most extensive experience and has reported the results of their first 40 adult-to adult living-donor liver transplantations, performed between June 1998 and October 1999.  There were an equal number of related and unrelated donors.  Minor complications occurred in seven donors.  The outcomes among recipients were similar to those associated with cadaveric donor livers performed during the same period of time.  However, in the initial series of 20 patients, four of the five deaths occurred in recipients who were classified as Status 2A (see Description section).  In the subsequent 20 patients, recipients classified as Status 2A were not considered candidates for living-donor transplant.  Other case series have reported similar success rates.  Reports of several donor deaths re-emphasize the importance of careful patient selection based in part on a comprehensive consent process and an experienced surgical team.  In December 2000, the National Institutes of Health convened a workshop focusing on living-donor liver transplantation.  A summary of this workshop was published in 2002.  According to this document, the risk of mortality to the donor undergoing right hepatectomy was estimated to be approximately 0.2%-0.5%.  Based on survey results, the workshop reported that donor morbidity was common; 7% required re-exploration, 10% had to be re-hospitalized, and biliary tract complications occurred in 7%.  The median complication rate reported by responding transplant centers was 21%.

Due to the potential morbidity and mortality experienced by the donor, the workshop also noted that donor consent for hepatectomy must be voluntary and free of coercion; therefore, it was preferable that the donor have a significant long-term and established relationship with the recipient.  According to the workshop summary, “At the present time, nearly all centers strive to identify donors who are entirely healthy and at minimal risk during right hepatectomy.  As a result, only approximately one third of persons originally interested in becoming a living liver donor complete the evaluation process and are accepted as candidates for this procedure.”

Criteria for a recipient of a living-related liver are also controversial, with some groups advocating that living-related donor livers be only used in those most critically ill; while others state that the risk to the donor is unacceptable in critically ill recipients due to the increased risk of postoperative mortality of the recipient.  According to this line of thought, living-related livers are best used in stable recipients who have a higher likelihood of achieving long-term survival.

In 2000, the American Society of Transplant Surgeons issued the following statement:

“Living donor transplantation in children has proven to be safe and effective for both donors and recipients and has helped to make death on the waiting list a less common event.  Since its introduction in 1990, many of the technical and ethical issues have been addressed and the procedure is generally applied.

The development of left or right hepatectomy for adult-to-adult living-donor liver transplantation has been slower.  Because of the ongoing shortage of cadaver livers suitable for transplantation, adult-to-adult living-donor liver transplantation has been undertaken at a number of centers. While early results appear encouraging, sufficient data are not available to ascertain donor morbidity and mortality rates.  There is general consensus that the health and safety of the donor is and must remain central to living organ donation.”

A review of the literature based on the MEDLINE database for the period of 2002 through September 2006 did not identify any articles that would prompt reconsideration of the above policy.  There is ongoing discussion of living-related adult-to-adult liver transplantation.  Brown and colleagues reported on the results of a survey focusing on adult living-related recipients in the United States (U.S.).  The following statistics were reported:

  • The survey encompasses 449 adult-to-adult transplantations.
  • Half of the responding programs already had performed at least one adult-to-adult living-donor liver transplantation, and 32 of the remaining 41 centers were planning to initiate such surgery.
  • 14 centers had performed more than ten such transplantations, and these centers accounted for 80% of these transplants.
  • A total of 45% of those evaluated for living donation subsequently donated a liver lobe; 99% were genetically or emotionally related to the recipient.
  • Complications in the donor were more frequent in the centers that performed the fewest living-related donor transplantations.
  • There was one death among the donors, but complications were relatively common, i.e., biliary complications in 6% and reoperation in 4.5%.

In 2002, the National Institutes of Health sponsored a conference on living-donor liver transplantation.  This report offered the following observations:

  • The incidence and type of complications encountered and mortality associated with living-donor liver transplant in both donors and recipients needs to be determined and compared with that for patients undergoing cadaveric transplantation.
  • The question of whether all U.S. transplant programs should perform this operation or this complex procedure should be limited to only a few select centers needs to be addressed.

Human Immunodeficiency Virus Positive (HIV+) Patients

This subgroup of recipients has long been controversial, due to the long-term prognosis for human immunodeficiency virus (HIV) positivity, the impact of immunosuppression on HIV disease, and the interactions of immunosuppressive therapy with antiretroviral therapy in the setting of a transplanted liver.  For example, most antiretroviral agents are metabolized through the liver and can cause varying degrees of hepatotoxicity.  HIV candidates for liver transplantation are frequently co-infected with hepatitis B or C, and viral co-infection can further exacerbate drug-related hepatotoxicities.  Although HIV+ transplant recipients may be a research interest of some transplant centers (i.e., the University of Pittsburgh, University of Miami, and the University of California at San Francisco), the minimal data regarding long-term outcome in these patients consist primarily of case reports and abstract presentations.  Nevertheless, some liver transplant surgeons would argue that HIV positivity is no longer an absolute contraindication to liver transplant due to the advent of highly active antiretroviral therapy (HAART), which has markedly changed the natural history of the disease, and the increasing experience with liver transplant in HIV+ patients.  Furthermore, UNOS states that asymptomatic HIV+ patients should not necessarily be excluded for candidacy for organ transplantation, stating “A potential candidate for organ transplantation whose test for HIV is positive but who is in an asymptomatic state should not necessarily be excluded from candidacy for organ transplantation, but should be advised that he or she may be at increased risk of morbidity and mortality because of immunosuppressive therapy.  In 2001, the Clinical Practice Committee of the American Society of Transplantation proposed that the presence of AIDS could be considered a contraindication to kidney transplant unless the following criteria were present.  These criteria may be extrapolated to other organs:

  • CD4 count >200 cells/mm-3 for >6 months (CD4 is an antigenic marker on T cells);
  • HIV-1 RNA undetectable (viral load, i.e., level of viral genetic material (RNA) present in blood plasma);
  • On stable anti-retroviral therapy more than 3 months;
  • No other complications from AIDS (e.g., opportunistic infection, including aspergillus, tuberculosis, coccidioses mycosis, resistant fungal infections, Kaposi’s sarcoma, or other neoplasm); and
  • Meeting all other criteria for transplantation.

It is likely that each individual transplant center will have explicit patient selection criteria for HIV+ patients.  In addition, there is an ongoing multi-institutional prospective study of liver and kidney transplantation in HIV+ recipients.  The target enrollment is 150 kidney transplant recipients and 125 liver transplant recipients.  The goals of the trial are described as follows:

“Primary aims of the study are to assess the impact of iatrogenic immunosuppression on patient survival and to assess the impact of HIV infection and antiretroviral treatment on graft survival, including in the setting of HBV or HCV [hepatitis C virus] coinfection and HIV-associated nephropathy.  Secondary aims include assessment of the effect of immunosuppressant therapy on CD 4+ cell counts, HIV RNA levels, and opportunistic complications; exploration of the relationships among disease development, the host immune response and viral evolution with regard to HBV, HCV, CMV, herpes virus-8 and human papilloma virus (HPV); assessment of the impact of HIV infection on alloimmune response and graft rejection rates; and analysis of pharmacokinetic interactions between immunosuppressant drugs and hepatically metabolized antiretroviral agents.”

2009 Update

A literature search was conducted seeking evidence on two main issues: 1) whether selection criteria for hepatocellular carcinoma (HCC) should be expanded, and 2) whether cholangiocarcinoma (CCA) should be considered an acceptable indication for liver transplantation. 

Hepatocellular Carcinoma (HCC)

Questions on patient selection criteria for HCC have focused mainly on the number and size of tumors.  An editorial by Llovet noted that the Milan criteria are considered the gold standard and specify that patients may either have a solitary tumor with a maximum tumor diameter of 5 cm or less, or up to three tumors 3 cm or smaller.  A 2001 paper from the University of California, San Francisco (UCSF), proposed expanded criteria, to include patients with a single tumor up to 6.5 cm in diameter, three or fewer tumors with maximum size 4.5 cm, and a total tumor size of 8 cm or less.  It should be noted that either set of criteria can be applied preoperatively (with imaging) or with pathology of the explanted liver at the time of intended transplant.  Preoperative staging often underestimates what is seen on surgical pathology.  To apply pathologic criteria, a backup candidate must be available in case preoperative staging is inaccurate.  Given donor organ scarcity, any expansion of liver transplant selection criteria has the potential to prolong waiting times for all candidates.  Important outcomes in assessing expanded criteria include waiting time duration, death or deselection due to disease progression while waiting (dropout), survival time, and time to recurrence (or related outcomes such as disease-free survival).  Survival time can be estimated beginning when the patient is placed on the waiting list, using the intention-to-treat principal, or at the time of transplantation.  Llovet stated that 1-year dropout rates for patients meeting Milan criteria are 15%–30% and 5-year survival rates not reported by intention-to-treat should be adjusted down by 10%–15%.

A very limited body of evidence is available for outcomes among patients exceeding Milan criteria but meeting UCSF criteria.  The largest series was conducted in 14 centers in France, including an intention-to-treat total of 44 patients based on preoperative imaging at the time of listing, and a subset of 39 patients meeting pathologic UCSF criteria.  The median waiting time was 4.5 months, shorter than the typical 6–12 months in North America.  Dropouts composed 11.4%.  Post-transplant overall patient 5-year survival, at 63.6%, was more favorable than the intention-to-treat probability (45.5%), but less favorable than among larger numbers of patients meeting Milan criteria.  Similar findings were seen for disease-free survival and cumulative incidence of recurrence.  Three centers in Massachusetts included 10 patients beyond pathologic Milan criteria but within UCSF criteria.  Two-year survival post-transplant was 77.1%, with two patients dying and eight alive after a median of 32 months.  A group of 74 patients meeting preoperative Milan criteria had a 2-year survival probability of about 73%, but it is inadvisable to compare different preoperative and pathologic staging criteria.  From the series of patients that developed the expanded UCSF criteria, 14 satisfied those criteria on pathology but exceeded the Milan criteria.  UCSF investigators do not provide survival duration data for this subgroup, but note that two patients died.  A center in Essen, Germany, reported on four patients.  Although the French series suggests that outcomes among patients exceeding Milan criteria and meeting UCSF criteria are worse than for patients meeting Milan criteria, it is unclear if the latter group still achieves acceptable results.  A benchmark of 50% 5-year survival has been established in the liver transplant community, and the French study meets this by post-transplant pathologic staging results (63.6%) and falls short by preoperative intention-to-treat results (45.5%).  Centers in the United States have published data for only 24 patients exceeding Milan criteria and meeting UCSF criteria; survival and recurrence data are very sparse.  Overall, the evidence base is insufficient to permit conclusions about health outcomes after liver transplantation among patients exceeding Milan criteria and meeting expanded UCSF criteria.

The evolution of selection criteria continues to be a focus in the literature.  In their 2008 review, Schwartz and colleagues argue that selection based exclusively on the Milan criteria risks prognostic inaccuracy due to the diagnostic limitations of imaging procedures and the surrogate nature of size and number of tumors.  They predict that evolution of allocation policy will involve the following: 1) the development of a reliable prognostic staging system to help with allocation of therapeutic alternatives; 2) new molecular markers that might improve prognostic accuracy; 3) aggressive multimodality neoadjuvant therapy to downstage and limit tumor progression before transplant and possibly provide information about tumor biology based on response to therapy; and, 4) prioritization for transplantation should consider response to neoadjuvant therapy, time on waiting list, suitability of alternative donor sources.  Two papers describe work on identifying predictors of survival and recurrence of disease.  Ioannou and colleagues analyzed UNOS data pre- and post-adoption of the MELD allocation system finding a 6-fold increase in recipients with HCC, and that survival in the MELD era was similar to survival to patients without HCC.  The subgroup of patients with larger (3-5 cm) tumors, serum alpha-fetoprotein level >455 mg/mL, or a MELD score >20, however, had poor transplantation survival.  A predicting-cancer-recurrence scoring system was developed by Chan et al. based on a retrospective review and analysis of liver transplants at two centers to determine factors associated with recurrence of HCC.  Of 116 patients with findings of HCC in their explanted livers, 12 developed recurrent HCC.  Four independent significant explant factors were identified by stepwise logistic regression: size of one tumor >4.5 cm, macroinvasion, and bilobar tumor were positive predictors of recurrence, and the presence of only well-differentiated HCC was a negative predictor.  Points were assigned to each factor in relation to its odds ratio.  The accuracy of the method was confirmed in two validation cohorts.

Cholangiocarcinoma (CCA)

Data are similarly sparse on outcomes after liver transplantation for CCA, or bile duct carcinoma.  A MEDLINE search was conducted seeking data from patient series of 20 or more.  The search identified evidence from two international registries, one multicenter report from Spain, and four individual centers, three of which are in the United States.  Reports generally distinguish between intrahepatic and extrahepatic tumors, the latter including hilar or perihilar tumors.  Recent efforts have focused on pretransplant downstaging of disease with neoadjuvant radiochemotherapy.  Relevant outcomes include waiting time duration, dropout rates, survival time, and recurrence.

The European Liver Transplant Registry was cited by a review article.  Among 186 patients with intrahepatic CCA, 1-year survival was 58% and 5-year survival was 29%.  In 169 patients with extrahepatic CCA, the probabilities were 63% and 29%.  The Cincinnati Transplant Registry reported on 207 patients with either intrahepatic or extrahepatic CCA, finding a 1-year survival of 72% and a 5-year rate of 23%.  The multicenter Spanish report included 36 patients with hilar tumors and 23 with peripheral intrahepatic disease.  One-year survival was 82% and 77%, while 5-year survival was 30% and 23%, in the two groups, respectively.

Among the individual centers, the Mayo Clinic in Minnesota has the most experience and most favorable results.  Between 1993 and 2006, 65 patients underwent liver transplantation for unresectable perihilar CCA or had perihilar tumor due to primary sclerosing cholangitis (PSC).  Patients with unresectable cancer underwent neoadjuvant radiochemotherapy.  One-year survival was 91% and 5-year survival was 76%.  The University of California, Los Angeles (UCLA)/Cedars-Sinai, reported on 25 cases of both intrahepatic and extrahepatic CCA.  One-year survival was 71% and 3-year survival was 35%.  The University of Pittsburgh found 1-year survival of 70% and 18% 5-year survival among 20 patients with intrahepatic CCA.  A German study of 24 patients reported the poorest results.

Only two articles reported recurrence data using survival analysis techniques.  In a series of 38 patients from the Mayo Clinic, cumulative recurrence was 0% at 1 year, 5% at 3 years, and 13% at 5 years.  The series of 20 patients from the University of Pittsburgh experienced 67% 1-year tumor-free survival and a 31% 5-year rate.  The multicenter Spanish series reported crude recurrence rates of 53% and 36% for extrahepatic and intrahepatic CCA, respectively.  The German center at Hannover found a crude recurrence rate of 63%.

The Mayo Clinic remains the only center that has published outcome data for transplantation following neoadjuvant radiochemotherapy.  In a 2008 review, Heimbach considers the published outcomes of the combined protocol in the context of recent data on outcomes for surgical resection, and concludes that outcomes of neoadjuvant chemoradiotherapy with subsequent liver transplantation for patients with early-stage hilar CCA that is unresectable, or arising in the setting of PSC, are comparable to transplantation for patients with HCC and other chronic liver diseases and superior to resection.  The author describes intraoperative challenges attributable to the neoadjuvant therapy including severe inflammatory changes and dense fibrosis and suggests that key principles to be considered by centers considering use of the combined protocol include a multidisciplinary approach, pretransplant staging, inclusion of only patients without lymph node metastasis, replacement of irradiated vessels (when possible) and monitoring for postoperative vascular complications.  Wu et al. describe an extensive surgical procedure combined with radiotherapy.  They retrospectively review their experience with surveillance and early detection of CCA and en bloc total hepatectomy-pancreaticoduodenectomy-orthotopic liver transplantation (OLT-Whipple) in a small series of patients with early stage CCA complicating PSC.  Surveillance involved endoscopic ultrasound, endoscopic retrograde cholangiopancreatography, and cytological evaluation.  Patients diagnosed with CCA were treated with combined extra-beam radiotherapy, lesion-focused brachytherapy, and OLT-Whipple.  CCA was detected in eight of the 42 patients followed up according to the surveillance protocol between 1988 and 2001, and six patients underwent OLT-Whipple.  One died at 55 months after transplant of an unrelated cause without tumor recurrence, and five are without recurrence at 5.7–10.1 years.

In June, 2009, UNOS amended Policy 3.6 Allocation of Livers to state that candidates with cholangiocarcinoma may be eligible for a MELD/PELD exception when the following criteria are met:

  • Centers must submit a written protocol for patient care to the OPTN/UNOS Liver and Intestinal Organ Transplantation Committee before requesting a MELD score exception for a candidate with CCA.  This protocol should include selection criteria, administration of neoadjuvant therapy before transplantation, and operative staging to exclude patients with regional hepatic lymph node metastases, intrahepatic metastases, and/or extrahepatic disease. The protocol should include data collection as deemed necessary by the OPTN/UNOS Liver and Intestinal Organ Transplantation Committee.
  • Candidates must satisfy diagnostic criteria for hilar CCA: malignant-appearing stricture on cholangiography and biopsy or cytology results demonstrating malignancy, carbohydrate antigen 19-9 100 U/mL, or aneuploidy.  The tumor should be considered unresectable on the basis of technical considerations or underlying liver disease (e.g., primary sclerosing cholangitis).
  • If cross-sectional imaging studies (CT scan [computed tomography], ultrasound, MRI [magnetic resonance imaging]) demonstrate a mass, the mass should be 3 cm.
  • Intra- and extra-hepatic metastases should be excluded by cross-sectional imaging studies of the chest and abdomen at the time of initial exception and every three months before score increases.
  • Regional hepatic lymph node involvement and peritoneal metastases should be assessed by operative staging after completion of neoadjuvant therapy and before liver transplantation. Endoscopic ultrasound-guided aspiration of regional hepatic lymph nodes may be advisable to exclude patients 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.

Hepatitis C (HCV)

Mukherjee and Sorrell, reviewing controversies in liver transplantation for hepatitis C, indicate that the greatest opportunity for HCV eradication is pretransplant before hepatic decompensation.  Challenges of treatment post-transplantation include immunosuppressive drugs, and abnormal hematologic, infectious, and liver function parameters.  The authors list the following factors associated with poor outcomes in liver transplantation for recurrent HCV: high HCV-RNA level pretransplant, non-caucasian ethnicity, advanced donor age, T-cell depleting therapies, inappropriate treatment of Banff A1 ACR with steroid boluses, cytomegalovirus disease, and year of transplantation (worse with recent transplants).  They cite the International Liver Transplantation Society Consensus on Retransplantation, which states that the following are associated with worse outcomes of retransplantation: total bilirubin level >10mg/dL, creatinine level >2 mg/dL, age >55 years, development of cirrhosis in the first post-transplant year, and donor age >40 years.

Coding

Disclaimer for coding information on Medical Policies           

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy.  They may not be all-inclusive.           

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.           

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps. 

ICD-9 Codes

Refer to the ICD-9-CM manual.

ICD-10 Codes
B15.0 – B15.9, B16.0 – B16.9, B17.0 – B17.9, B18.0 – B18.9, B19.0 – B19.9, B25.1, B66.1, B66.5, C22.0 – C22.9, D64.0 – D64.9, D81.810, D84.0 – D84.9, E72.00 – E72.09, E74.00 – E74.9, E78.0 – E78.9, E80.0 – E80.7, E83.0 – E83.09, E83.1 – E83.19, E85.0 – E85.9, E88.9, G60.0 – G60.9, I82.0, I99.9, K71.10 – K71.9, K74.0 – K74.69, K77, K83.0 – K83.9, Q44.6, S36.12xA - S36.13xS, Z52.6, 0FB00ZZ, 0FB03ZZ, 0FB04ZZ, 0FB10ZZ, 0FB13ZZ, 0FB14ZZ, 0FB20ZZ, 0FB23ZZ, 0FB24ZZ, 0FT00ZZ, 0FT04ZZ, 0FY00Z0, 0FY00Z1 
Procedural Codes: 47133, 47135, 47136, 47140, 47141, 47142, 47143, 47144, 47145, 47146, 47147, 81370, 81371, 81372, 81373, 81374, 81375, 81376, 81377, 81378, 81379, 81380, 81381, 81382, 81383, 86805, 86806, 86807, 86808, 86812, 86813, 86816, 86817, 86821, 86822, 86825, 86826, 86849
References
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  2. Casavilla FA, Marsh JW, Iwatsuki S et al. Hepatic resection and transplantation for peripheral cholangiocarcinoma. J Am Coll Surg 1997; 185(5):429-36.
  3. Wachs, M.E., et al.  Adult living donor liver transplantation using a right hepatic lobe. Transplantation (1998 November 27) 66(10): 1313-6.
  4. Ragni, M.V., Dodson, S.F., et al.  Liver transplantation in a hemophilia patient with acquired immunodeficiency syndrome.  Blood (1999) 93(3):1113-5.
  5. Inomata, Y., et al.  Right lobe graft in living donor liver transplantation.  Transplantation (2000 January 27) 69(2): 258-64.
  6. Fan, S.T., et al.  Safety of donors in live donor liver transplantation using right lobe grafts. Archives of Surgery (2000 March) 135(3): 336-40.
  7. Marcos, A., et al.  Single-center analysis of the first 40 adult-to-adult living donor liver transplants using the right lobe.  Liver Transplant (2000 May) 6(3): 296-301.
  8. American Society of Transplant Surgeons' position paper on adult-to-adult living donor liver transplantation.  Liver Transplant (2000) 6(6):815-7.
  9. Renz, J.F. and R.W. Busuttil.  Adult-to-adult living-donor liver transplantation: a critical analysis. Seminars in Liver Disease (2000) 20(4):411-24.
  10. Meyer CG, Penn I, James L. Liver transplantation for cholangiocarcinoma: results in 207 patients. Transplantation 2000; 69(8):1633-7.
  11. Weimann A, Varnholt H, Schlitt HJ et al. Retrospective analysis of prognostic factors after liver resection and transplantation for cholangiocellular carcinoma. Br J Surg 2000; 87(9):1182-7.
  12. Kamath, P.S., Wiesner, R.H., et al.  A model to predict survival in patients with end-stage liver disease.  Hepatology (2001) 33(2):464-70.
  13. Bak, T., Wachs, M., et al.  Adult-to-adult living donor liver transplantation using right-lobe grafts: results and lessons learned from a single-center experience. Liver Transplant (2001) 7(8):680-6.
  14. Malago, M., Testa, G., et al.  Ethical considerations and rationale of adult-to-adult living donor liver transplantation.  Liver Transplant (2001) 7(10):921-7.
  15. Gow, P.J. and D. Mutimer.  Liver transplantation for an HIV-positive patient in the era of highly active antiretroviral therapy.  AIDS (2001) 15(2):291-2.
  16. Steinman, T.I., Becker, B.N., et al.  Guidelines for the referral and management of patients eligible for solid organ transplantation.  Transplantation (2001) 71(9):1189-204.
  17. Yao FY, Ferrell L, Bass NM et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology 2001; 33(6):1394-403.
  18. Shimoda M, Farmer DG, Colquhoun SD et al. Liver transplantation for cholangiocellular carcinoma: analysis of a single-center experience and review of the literature. Liver Transpl 2001; 7(12):1023-33.
  19. Shiffman, M.L., Brown, R.S., et al.  Living donor liver transplantation: summary of a conference at the National Institutes of Health. Liver Transplant (2002) 8(2):174-88.
  20. Neff, G.D., Jayaweera, D., et al.  Liver transplantation for HIV-infected patients with end-stage liver disease.  Current Opinion in Organ Transplant (2002) 7(2):114-23.
  21. Roland, M.E., Carlson, L., et al.  Solid organ transplantation in HIV-infected recipients: a review of 53 cases in the HAART-era.  XIV International AIDS Conference. Barcelona, Spain (2002).
  22. Yao FY, Ferrell L, Bass NM et al. Liver transplantation for hepatocellular carcinoma: comparison of the proposed UCSF criteria with the Milan criteria and the Pittsburgh modified TNM criteria. Liver Transpl 2002; 8(9):765-74.
  23. Brown, R.S., Russo, M.W., et al.  A survey of liver transplantation from living adult donors in the United States.  New England Journal of Medicine (2003 February 27) 348(9): 818-825.
  24. Pascher A, Jonas S, Neuhaus P. Intrahepatic cholangiocarcinoma: indication for transplantation. J Hepatobiliary Pancreat Surg 2003; 10(4):282-7.
  25. Policies and Bylaws.  United Network for Organ Sharing.  Alexandria, VA. (2004) www.unos.org/frame .
  26. Roland, M.E.  Solid-organ transplantation in HIV-infected patients in the potent antiretroviral therapy era.  Top HIV Medicine (2004) 12(3):73-6.
  27. Leung JY, Zhu AX, Gordon FD et al. Liver transplantation outcomes for early-stage hepatocellular carcinoma: results of a multicenter study. Liver Transpl 2004; 10(11):1343-54.
  28. Robles R, Figueras J, Turrion VS et al. Spanish experience in liver transplantation for hilar and peripheral cholangiocarcinoma. Ann Surg 2004; 239(2):265-71.
  29. 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):451-61.
  30. Ueno, T., Barri, Y.M., et al.  Liver and kidney transplantation for polycystic liver and kidney-renal function and outcome.  Transplantation (2006 August 27) 82(4):501-7.
  31. Literature  search current through October 2006.
  32. Llovet JM. Expanding HCC criteria for liver transplant: the urgent need for prospective, robust data. Liver Transpl 2006; 12(12):1741-3.
  33. Decaens T, Roudot-Thoraval F, Hadni-Bresson S et al. Impact of UCSF criteria according to pre- and post-OLT tumor features: analysis of 479 patients listed for HCC with a short waiting time. Liver Transpl 2006; 12(12):1761-9.
  34. Sotiropoulos GC, Molmenti EP, Omar OS et al. Liver transplantation for hepatocellular carcinoma in patients beyond the Milan but within the UCSF criteria. Eur J Med Res 2006; 11(11):467-70.
  35. Heimbach JK, Gores GJ, Haddock MG et al. Predictors of disease recurrence following neoadjuvant chemoradiotherapy and liver transplantation for unresectable perihilar cholangiocarcinoma. Transplantation 2006; 82(12):1703-7.
  36. Heimbach JK. Successful live transplantation for hilar cholangiocarcinoma. Curr Opin Gastroenterol 2008; 24(3)-384-8.
  37. Wu Y, Johlin FC, Rayhill SC et al. Long-term, tumor-free survival after radiotherapy combining hepatectomy-Whipple en bloc and orthotopic liver transplantation for early-stage hilar cholangiocarcinoma. Liver Transpl 2008; 14(2):279-86.
  38. Schwartz ME, D’Amico F, Vitale A et al. Liver transplantation for hepatocellular carcinoma: are the Milan criteria still valid? Eur J Surg Oncol 2008; 34(3):256-62.
  39. Ioannou GN, Perkins JD, Carithers RL Jr. Liver transplantation for hepatocellular carcinoma: Impact of the MELD allocation system and predictors of survival. Gastroenterology 2008; 134(5):1342-51.
  40. Chan EY, Larson AM, Fix OR. Identifying risk for recurrent hepatocellular carcinoma after liver transplantation: implications for surveillance studies and new adjuvant therapies. Liver Transpl 2008; 14(7):956-65.
  41. Mukherjee S, Sorrell MF. Controversies in liver transplantation for hepatitis C. Gastroenterology 2008; 134(6):1777-88.
  42. Liver Transplant.  Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2008 November) Surgery 7.03.06.
  43. United Network for Organ Sharing Organ Distribution.  Policy 3.6 Allocation of Livers (2009 June 23) 3.6: 1-19. UNOS Web Site: http://www.unos.org .
History
January 2012 Policy updated with literature search, reference numbers 15, 23-24, 34, 38 and 40-41 added. Policy statements for medically necessary indications unchanged; neuroendocrine tumor metastases added to investigational statement. Policy statements on hepatocellular carcinoma that has extended beyond the liver and ongoing alcohol and/or drug abuse moved from investigational to not medically necessary. Removed “Patients with an active infection” from the investigational policy statement. 
October 2013 Policy formatting and language revised.  Added cryptogenic cirrhosis to the medically necessary hepatocellular diseases.  Added the statement: "Liver transplant may be considered medically necessary for patients with early stage cholangiocarcinoma (CCA) that is unresectable or arising in the setting of underlying PSC, when Mayo protocol is/will be followed; and UNOS (United Network of Organ Sharing) criteria for transplant with CCA diagnosis have been met".
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Liver Transplant