Liver Transplantation

Coverage Summary

This policy part is covered with criteria for orthotopic liver transplantation (OLT) and related procedures: it defines candidate selection (age-based rules using MELD/PELD thresholds, UNOS Regional Review Board or institutional selection criteria), lists covered diagnoses and examples of medically necessary indications (cholestatic, hepatocellular, vascular, metabolic, malignancy indications, fulminant hepatic failure, trauma, hepato-pulmonary syndrome), permits retransplantation when the initial transplant was for a covered indication, enumerates absolute contraindications, and identifies interventions considered experimental/investigational (e.g., bioartificial liver, MARS, machine perfusion modalities, xenotransplantation, everolimus). The part also contains the CPT/HCPCS/ICD-10 code lists that are covered when selection criteria are met and notes CPT/HCPCS items not covered. Criteria require documentation of MELD or PELD scores, UNOS or institutional approvals when applicable, and exclusion for absolute contraindications.

Key thresholds & policy dates

MELD rule> 10 required for adolescents >=12 and adults to meet primary eligibility (otherwise UNOS RRB approval or institutional criteria required)

Hepato-pulmonary syndrome - PaO2PaO2 < 60 mm Hg (plus other HPS criteria required)

Hepato-pulmonary syndrome - AaO2 gradientAaO2 gradient > 20 mm Hg (in supine or standing position)

Porto-pulmonary hypertension - mPAPMean pulmonary artery pressure by catheterization < 35 mm Hg

PLR cut-offPlatelet-to-lymphocyte ratio commonly reported cut-off = 150

Transient elastography (examples)Study-reported TE cut-offs varied (e.g., >7.9 kPa, >8.5 kPa to indicate graft damage; reported range ~7.3–12.3 kPa)

OrganOx Metra donor limitsDBD or DCD donors ≤ 40 y; functional warm ischemic time ≤ 20 min; macro-steatosis ≤ 15%; intended preservation up to 12 h (device supports up to 24 h)

Policy datesEffective: 2002-03-05; Last review: 2023-08-09; Next review: 2024-06-27

Medical-Necessity Criteria

Medical Necessity - Candidate Eligibility

Covered when ALL of the following are met:

Medical Necessity - Candidate Eligibility (top)

Age group and approvals
- Adolescents (>=12) and adults: Adolescents 12 years of age or older and adults: one of: MELD score greater than 10; OR approved for transplant by the UNOS Regional Review Board; OR meet the transplant institution's selection criteria>10 (MELD)
  MELD/PELD definitions and guidance in Appendix
- Children <12: Children less than 12 years of age who meet the transplanting institution's selection criteriaPELD per institution

Coding

CPT codes covered if selection criteria are metCPTCovered

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; without trisegment or lobe split.
47144	With trisegment split of whole liver graft into two partial liver grafts.
47145	With lobe split of whole liver graft into two partial liver grafts.
47146	Backbench reconstruction of cadaver or living donor liver graft prior to allotransplantation; venous anastomosis, each.
47147	Arterial anastomosis, each.

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CPT/HCPCS codes not covered (procedures/interventions listed as experimental/investigational)mixedNot Covered

no_specific_code	Molecular Adsorbent Recirculating System (MARS) - no specific code
no_specific_code	Normothermic machine perfusion of donor liver - no specific code
no_specific_code	Hypothermic machine perfusion - no specific code
no_specific_code	Scaffold-based transplantation - no specific code
no_specific_code	OrganOx metra System - no specific code

HCPCS codes not coveredHCPCSNot Covered

B4155	Enteral formula, nutritionally incomplete/modular nutrients, administered through an enteral feeding tube, 100 calories = 1 unit.
J0480	Injection, basiliximab, 20 mg.
J2598	Injection, vasopressin, 1 unit.
J2599	Injection, vasopressin (american regent) not therapeutically equivalent to j2598, 1 unit.

ICD-10 codes covered if selection criteria are metICD-10Covered

B16.0
B16.2
B18.0
B18.1
B19.11	Acute hepatitis B with hepatic coma.
B16.1
B16.9
B19.10	Acute hepatitis B without mention of hepatic coma.
B17.10	Acute hepatitis C without hepatic coma.
B17.11	Acute hepatitis C with hepatic coma.

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ICD-10 codes not covered for indications listedICD-10Not Covered

A41.9	Sepsis, unspecified organism.
C24.0	Malignant neoplasm of extrahepatic bile duct.
Z76.82	Awaiting organ transplant status [liver].
Z94.4	Liver transplantation status [not covered for the use of everolimus to prevent organ rejection].

Provider Actions & Requirements

Prior Authorization

Medical necessity review when institutional criteria absent or MELD <=10

Medical necessity review required when institutional selection criteria are not provided, or for adolescents and adults with a MELD score of 10 or less who have not been approved by the UNOS Regional Review Board.

Documentation Required

Document MELD/PELD, UNOS approval, and institution selection criteria

Document MELD/PELD scores, UNOS Regional Review Board approval (when applicable), and that the member meets the transplanting institution's selection criteria.

Background & Evidence Summary

Background rationale: liver transplantation is an effective therapy for fulminant hepatic failure and many chronic and metabolic liver diseases; MELD (adults) and PELD (children) scoring systems are used to prioritize candidates and identify urgency, with MELD scores <10 rarely requiring transplant and UNOS Regional Review Boards available to approve exceptions. Pediatric considerations include frequent use of reduced-size, split, and living-donor left-lobe grafts to address donor scarcity and size mismatch. Emerging and assessed technologies/interventions summarized include bioartificial liver systems and albumin-dialysis (MARS) with mixed survival impacts but improvements in bilirubin and encephalopathy; normothermic machine perfusion (NMP-L), hypothermic/sub-normothermic machine perfusion (HMP/SNMP) and hypothermic oxygenated perfusion (HOPE) with potential for better preservation and reduced biliary complications versus static cold storage but requiring more RCT data; OrganOx Metra and NRP strategies for extended preservation; peri-operative therapies evaluated include sorafenib (no clear survival benefit), ursodeoxycholic acid (no prevention of acute cellular rejection), peri-operative immuno-nutrition (some reduction in infections and shorter stays), vasopressin/terlipressin (limited renal benefit evidence), and immunosuppression agents including basiliximab and everolimus (basiliximab evidence limited/low-certainty; everolimus not recommended by NICE for prevention of rejection). Xenotransplantation, scaffold-based transplantation, hepatocyte transplantation and several perfusion/transport devices are considered investigational.

Evidence Item	Key Finding
MARS randomized trials/meta-analyses	Meta-analyses and RCTs show MARS reduces bilirubin and improves hepatic encephalopathy but overall no consistent mortality benefit; some meta-analyses show no significant mortality reduction (RR 0.56; 95% CI 0.28–1.14) while others show benefit in acute liver failure (RR 0.61; 95% CI 0.38–0.97)
HepatAssist bioartificial liver RCT (HepatAssist)	HepatAssist RCT (n=171) showed no overall significant survival benefit; marginal survival benefit for fulminant/subfulminant hepatic failure (risk ratio = 0.56; p=0.048)
NMP-L early clinical studies	Early clinical NMP-L trials demonstrated feasibility and safety with potential improved function vs static cold storage; RCT data pending and larger randomized studies needed
Hypothermic machine perfusion (HMP) / HOPE RCT results	Randomized trial of hypothermic oxygenated perfusion (HOPE) vs SCS in DCD livers showed reduced non-anastomotic biliary strictures (6% vs 18%; RR 0.36) and lower early allograft dysfunction (26% vs 40%; RR 0.61)
Machine perfusion (HMP/SNMP) pre-clinical mitochondrial protection	Animal data and network analyses indicate HMP and SNMP provide superior preservation of graft ATP and mitochondrial protection compared with other methods
NLR pre-transplant meta-analysis	Elevated pre-transplant neutrophil-to-lymphocyte ratio associated with worse OS (HR 2.22), recurrence-free survival (HR 3.77), and disease-free survival (HR 2.51) after LT for HCC
PLR pre-transplant meta-analysis	High pre-transplant platelet-to-lymphocyte ratio (commonly cut-off ~150) associated with increased post-transplant HCC recurrence (OR 3.33)
Transient elastography (TE) performance post-LT	TE performed best for detecting recurrent fibrosis post-LT (summary OR 21.17); reported cut-offs varied widely (7.3–12.3 kPa); small studies suggest cut-offs >7.9–8.5 kPa may indicate graft damage
IL-2 receptor and other biomarkers for acute rejection	Systematic review identified multiple biomarkers; IL-2 receptor had highest reported sensitivity (89%) and specificity (81%), but none replace biopsy
Basiliximab induction evidence	Network meta-analysis of RCTs (25 trials, 3,271 subjects) found low-certainty evidence basiliximab may lower all-cause mortality (HR 0.53) and graft failure (HR 0.44) versus glucocorticoid induction, but evidence is uncertain and trials at risk of bias
OrganOx Metra device summary	OrganOx metra is a transportable normothermic perfusion device supporting donor livers (DBD or DCD ≤40 y, functional warm ischemia ≤20 min, macro-steatosis ≤15%) and intended to sustain livers for total preservation times up to ~12 hours (device supports up to 24 h)

Definitions & Thresholds

Definitions:

MELD — Model for End-Stage Liver Disease; numerical scale (6–40) predicting 3-month mortality using bilirubin, prothrombin time and creatinine.

PELD — Pediatric End-stage Liver Disease scoring system for candidates under age 12, incorporating bilirubin, prothrombin time, albumin, growth failure, and age <1 year.

MARS — Molecular Adsorbent Recirculating System; an extracorporeal albumin dialysis device for liver support.

NMP-L — Normothermic Machine Perfusion of the Liver; organ preservation technique at physiologic temperature enabling viability assessment.

TE — Transient Elastography; noninvasive measurement of liver stiffness (reported in kPa).

NLR — Neutrophil-to-Lymphocyte Ratio; a pre-operative prognostic marker.

PLR — Platelet-to-Lymphocyte Ratio; a pre-operative prognostic marker (cut-off commonly reported as 150).

HMP — Hypothermic Machine Perfusion.

SNMP — Sub-normothermic Machine Perfusion.

NMP — Normothermic Machine Perfusion.

OLT — Orthotopic Liver Transplantation.

PE — Pulmonary Embolism.

Revision History

2002-03-05effective_date

Policy effective date: 2002-03-05.

2023-08-09last_review

Policy last reviewed on 2023-08-09.

2024-06-27next_reviewLatest

Next scheduled policy review on 2024-06-27.

Medically Necessary Indications (examples / not all-inclusive)

Orthotopic liver transplantation is medically necessary for ESLD due to any of the following when medical necessity criteria in Section I.A. are met:

Cholestatic diseases
- Biliary atresia
- Familial cholestatic syndromes
- Primary biliary cirrhosis
- PSC with secondary biliary cirrhosis: Primary sclerosing cholangitis with development of secondary biliary cirrhosis
Hepatocellular diseases
- Alcoholic cirrhosis
- Chronic active hepatitis with cirrhosis (hepatitis B or C)
- Cryptogenic cirrhosis
- Idiopathic autoimmune hepatitis
- Post-necrotic cirrhosis due to hepatitis B surface antigen negative state
Malignancies
- Primary HCC confined to liver: Primary hepatocellular carcinoma confined to the liver when ALL of the following are met: any lung metastases responsive to chemotherapy; member is not a candidate for subtotal liver resection; member meets UNOS criteria for tumor size and number; no identifiable extra-hepatic spread to lymph nodes, abdominal organs, bone or other sites; and no macrovascular involvementUNOS tumor size/number criteria
  Consistent with UNOS guidelines
- Hepatoblastoma (<12): Hepatoblastomas in members <12 years when ALL of the following are met: member is not a candidate for subtotal liver resection; member meets UNOS criteria for tumor size and number; there is no identifiable extra-hepatic spread to lungs, abdominal organs, bone or other sites (note: spread to veins and lymph nodes does not disqualify)UNOS criteria
  Pediatric note on venous/lymph node spread
- Epithelioid hemangioendotheliomas
Vascular diseases
- Budd-Chiari syndrome
- Veno-occlusive disease
Metabolic disorders
- Alpha-1-antitrypsin deficiency: Alpha 1-antitrypsin deficiency
- Hemochromatosis
- Inborn errors of metabolism
- Protoporphyria
- Wilson's disease
Miscellaneous
- Familial amyloid polyneuropathy
- Polycystic disease of the liver
- Porto-pulmonary hypertension with mean pulmonary artery pressure by catheterization < 35 mm Hgmean PAP < 35 mm Hg
Toxic and trauma
- Fulminant hepatic failure (toxic): Toxic reactions: Fulminant hepatic failure (e.g., mushroom poisoning, acetaminophen overdose)
- Trauma
Hepato-pulmonary syndrome when ALL of the following selection criteria are met: arterial hypoxemia (PaO2 < 60 mm Hg or AaO2 gradient > 20 mm Hg in supine or standing position); chronic liver disease with non-cirrhotic portal hypertension; and intrapulmonary vascular dilatation indicated by contrast-enhanced echocardiography, technetium-99 macroaggregated albumin perfusion scan, or pulmonary angiographyPaO2 < 60 mm Hg; AaO2 > 20 mm Hg

Experimental and Investigational (Not Covered)

The following interventions are considered experimental and investigational due to unestablished safety/effectiveness and are not covered:

Basiliximab for induction immunosuppression in individuals undergoing liver transplantation
Listed as investigational in policy
Bioartificial liver transplantation
Biomarkers for acute rejection: Biomarkers for diagnosis of acute allograft rejection including: acid labile nitroso-compounds (NOx), serum amyloid A protein, procalcitonin, peripheral blood T-cell activation, interleukin 2 (IL-2) receptor, guanylate-binding protein-2 mRNA, graft-derived cell-free DNA, pi-glutathione S-transferase, alpha-glutathione S-transferase and serum HLA class I soluble antigens
Ectopic or auxiliary liver transplantation
Everolimus to prevent rejection: Everolimus to prevent organ rejection after liver transplantation
NICE guidance not recommended
Factor V Leiden and F2 testing for member scheduled to receive partial liver transplant for primary sclerosing cholangitis
Hepatocyte transplantation: Hepatocellular (hepatocyte) transplantation
Hypothermic machine perfusion for reduction of early allograft dysfunction and biliary complications after LT
Listed investigational in policy despite emerging evidence
Liver transplantation for other malignancies: Liver transplantation for malignancies other than those listed as covered above
LT for extra-hepatic hilar cholangiocarcinoma: Liver transplantation for the treatment of extra-hepatic hilar cholangiocarcinoma
NGAL measurements: Measurements of plasma and urinary NGAL for predicting acute kidney injury following orthotopic liver transplantation
MARS for PFIC: Molecular Adsorbent Recirculating System (MARS) for treatment of progressive familial intrahepatic cholestasis
Normothermic machine perfusion of donor liver
OrganOx metra system: OrganOx metra System for transportation and preservation of the liver prior to transplantation
Device-specific criteria listed in background
Peri-operative vasopressin: Peri-operative use of vasopressin in liver transplantation
Peri-operative sorafenib: Peri-operative use of sorafenib in liver transplantation
Scaffold-based transplantation (combination of xeno-organ and cell transplantations)
Transient elastography for ACR: Transient elastography for diagnosis of acute cellular rejection following liver transplantation
Ursodeoxycholic acid to prevent ACR: Ursodeoxycholic acid (UDCA) as adjuvant to prevent acute cellular rejection after liver transplantation
Xenotransplantation