Randomized Controlled Trial of Transarterial Chemoembolization Versus Proton Beam Radiotherapy for the Treatment of Hepatocellular Carcinoma
Phase: NA
Conditions: Carcinoma, Hepatocellular
Sponsor: Loma Linda University

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 Randomized Controlled Trial of Transarterial 
Chemoembolization versus Proton Beam 
Radiotherapy for The Treatment of Hepatocellular 
Carcinoma  
 
 
NCT00857805  
 
 
3/5/2009 

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Randomized Controlled Trial of Transarterial Chemoembolization versus Proton Beam 
Radiotherapy for The Treatment of Hepatocellular Carcinoma 
 
 
 
 
 
 
 
 
 
Principal Investigator 
Michael deVera, MD 
Associate Professor of Medicine 
Director of Liver Transplant 
Loma Linda University Medical Center 
 
 
Co-Principal Investigator 
Dave Bush, MD 
Professor of Radiation Medicine 
Department of Radiation Medicine 
Loma Linda University Medical Center 
 
Investigators 
 
Michael Volk, MD 
Professor of Medicine 
Gastroenterology and Hepatology Division 
Loma Linda University Medical Center 
 
Jason Smith, MD 
Assistant Professor of Medicine 
Department of Radiology 
Loma Linda University Medical Center 
 
 
 
 
 
 
 
 
 

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Introduction 
Hepatocellular carcinoma (HCC) is one of the leading causes of death in patients with 
cirrhosis (1). It is the sixth most common neoplasm in the world, with more than a 
half million newly diagnosed cases annually (2,3).  The etiology is unknown but it is 
reported mainly in patients with cirrhosis and patients with chronic hepatitis B 
infection (HBV) (2).  Surgical resection and liver transplant are potential curative 
treatments for patients who meet Milan criteria (Appendix 1) or have  2cm solitary 
lesion (3,4).   
 
CT scan or Magnetic Resonance Imaging (MRI) of the abdomen with/without alpha 
fetoprotein (AFP) is an important tool for early detection.  HCC is diagnosed in 
patients with cirrhosis by one imaging technique showing a nodule larger than 2 cm 
with contrast uptake in the arterial phase and washout in venous or late phase, or 
two imaging techniques showing this radiological behavior for nodules of 1-2 cm in 
diameter (3).  Cytohistological confirmation is required for patients who do not fulfill 
these criteria (3,4).   
 
Multiple treatments are available. The best appropriate treatment is determined 
according to hepatic function reserve as represented by Child-Pugh-Turcotte class  
(Appendix 2), and tumor size and number.  Patients who are surgically fit with Child 
class A and solitary lesion  2 cm are best treated by tumor resection. Liver 
transplantation is the best treatment for patients with unresectable lesion(s) that 
meet the Milan criteria (5) (Appendix 1).    
 
Patients with tumor burden that exceeds Milan criteria are considered to receive one 
of the following locoregional treatments: transarterial chemoembolization (TACE), 
radiofrequency ablation (RFA), percutaneous ethanol injection and proton beam 
radiation (6).  The goals of these treatments are to control tumor growth, to 
downstage tumor size to meet Milan criteria, and to improve survival.  Patients who 
exceed the Milan criteria benefit from downstaging, so they can be qualified for liver 
transplant. Patients who meet Milan criteria benefit from tumor control to bridge 
them to liver transplantation (6,7).  TACE is considered the most common 
locoregional treatment that is used to treat HCC.  Proton beam radiotherapy has 
been used in treating HCC in a few centers across the globe.  Phase I and II trials 
showed a satisfactory safety and efficacy results.  Loma Linda University Medical 
Center is one of these pioneering centers that use proton beam as a treatment for 
HCC (ref).   This is the first randomized trial in the medical field that will compare 
head-to-head the efficacy of TACE versus proton beam in treating HCC patients.  
 
Transarterial Chemoembolization (TACE) 
Multiple studies have shown contradictory results regarding the efficacy of TACE in 
improving survival compared to other treatments.  The majority of these studies are 
retrospective studies or used a small sample of patients.  These contradictory results 
have been attributed to the difference in endpoints of these studies and the multiple 
variables such as tumor size and liver function that usually impact and confound the 
outcome.   

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In one large study involving several institutions in Italy, chemoembolization did not 
improve survival compared to supportive care only. Patients who did not undergo 
TACE lived as long as patients who received TACE, even though the tumors were 
more likely to shrink in size in patients who were treated (8).  Llovet et al. used 
TACE as a palliative treatment in a prospective, randomized controlled trial published 
in 2002 on 112 patients with intermediate stage HCC not felt to be candidates for 
other therapies.  The patients randomized to TACE versus supportive care only.  A 
significant increase in survival for the chemoembolization group was observed when 
compared with control (82% and 63%, 1-and 2-year survival, respectively, 
compared with 63% and 27%) (9).  A study in Japan has shown that TACE can 
downstage liver cancer (10). Downstaging created the option for transplant in some 
of these patients. Otherwise, these patients had tumors that were not operable 
(eligible for operation) or not qualified for liver transplantation because of the initial 
large size of their tumors (10). More importantly, this study showed an improvement 
in survival in patients whose tumors became considerably smaller. In the U.S., trials 
are underway to see whether doing TACE before liver transplantation increases 
patient survival as compared to liver transplantation without TACE.  Risk and 
common side effects of TACE include: bleeding, infection, worsening liver function, 
perforation of the common bile duct, veins or arteries, abdominal pain, nausea, 
vomiting, and fever.  
It is reasonable to conclude that TACE is a procedure with acceptable side effects and 
a controversial small advantage in improving survival, especially in patients with 
small tumor and for patients waiting for liver transplantation. TACE can be used only 
in patients with relatively preserved liver function. The reason for this is that these 
procedures, as mentioned previously, can lead to liver failure in individuals with poor 
liver function. 
 
Proton Beam Radiotherapy 
Proton beam radiotherapy has physical properties that target the actual tumor mass 
and spare large portions of nearby normal tissues.  Phase I and II trials 
demonstrated the safety of this treatment modality in decompensated patients with 
cirrhosis with HCC.  Few trials in Southeast Asia and the United States demonstrated 
that proton beam could be an effective treatment that may improve survival and 
control tumor progression. Tokuuye et al. treated 79 patients who had HCC with 
proton beam radiotherapy (12).  A median total dose of 72 Cobalt gray equivalents 
in 16 fractions was delivered. At 5 years, local tumor control and survival rates were 
89% and 27% respectively.  Kawashima et al.  used the same fractionation scheme 
in 30 patients with HCC with an indocyanine scheme green retention rate at 15 
minutes. Complete disappearance of tumors occurred in 24 patients (80%).  The 2-
year local regression-free rate in that study was 96%, and the 1-year and 3-year 
survival rates were 77% and 62% respectively (13).  Eight patients developed 
hepatic insufficiency, which presented as ascites, elevated transaminase levels, 
and/or asterixis from 1 to 4 months after therapy (13).  Bush et al., in a phase II 
trial where 34 patients with HCC completed 15 sessions of total 63 cobalt Gray 
equivalents, 75% local tumor control rate and overall survival rate of 55%.  Six 
patients underwent liver transplantation 6 to 18 months after proton therapy. In 2 
patients, there was no evidence of tumor pathology, demonstrating that proton 
therapy can eradicate HCC (14).  A complete pathologic response was also observed 
by Merle et al (15).  Risks involved in proton treatment include internal bleeding, 
radiation hepatitis (elevation in liver enzymes), worsening liver function (elevation in 

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bilirubin and INR) and perforation of the surrounding solid organ such as small bowel 
and stomach.   
 
Proton bean radiotherapy has been associated with some of the best outcomes in 
HCC patients; however, further studies are needed to compare proton to other 
treatments. 
 
In this randomized trial we wish to compare head-to-head the efficacy of proton 
beam radiotherapy versus TACE in treating patients with unresectable HCC.   
Aim of The Study 
This study aims to compare the efficacy of TACE versus proton beam radiotherapy in 
treating cirrhotic patients with HCC who meet San Francisco criteria.    
Study Design 
This is a randomized controlled trial targeting HCC patients at Loma Linda University 
Medical Center (LLUMC) and the Inland Empire area.  The diagnosis of HCC will be 
determined according to one abdominal imaging (CT scan or MRI) performed within 
3 months of randomization showing characteristics of HCC. These characteristics 
include including one or more nodules (2 cm) hypervascular or with contrast uptake 
in the arterial phase and washout in venous or late phase or two imaging techniques 
showing this radiological behavior for nodules of 1-2 cm in diameter.  An 
independent radiologist at LLUMC will verify the diagnosis of HCC.  Patients with 
cirrhosis with liver tumor that does not fulfill these criteria will need a 
cytopathological confirmation of HCC.   
 
The diagnosis of cirrhosis will be determined clinically and radiologically in patients 
with chronic liver disease by the presence of thrombocytopenia with or without 
coagulopathy, and splenomegaly with irregular liver surface with or without liver 
biopsy showing bridging fibrosis and regenerative nodules.    
  
Patients  
Patients with cirrhosis and HCC who are not candidates for surgical resection will be 
targeted for enrollment.  Patients will be recruited from the liver clinics at the 
Transplantation Institute and Faculty Medical Office.  Patients from the Inland Empire 
area will be invited to participate as well.  Community physicians will be informed of 
the study via mail and will be encouraged to refer their patients for participation (see 
attached letter No 1). Patients who are qualified to receive both TACE and proton 
treatments will be included.  CT scan of the chest and bone scan within 6 months is 
required to exclude the presence of metastasis. Macrovascular invasion will be 
excluded using MRI or CT scan of the abdomen that will be performed within 3 
months of enrollment.   
 
Interventional radiologists and a radiation oncologist at LLUMC will evaluate the 
patient’s case independently prior to randomization if the candidate is qualified to 
receive both treatments.  Contraindications to receive TACE are: Child class C, 
hypovascular lesion and active sepsis.  Contraindications to proton are: tense ascites 
requiring frequent paracentesis or proximity to a hollow organ such as the stomach 
or small intestine.   

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Inclusion Criteria 
1. Patients are candidates to receive both proton beam and TACE 
2. Patients with no evidence of metastasis or macrovascular invasion 
3. Patients with tumor burden that meets San Francisco criteria (Appendix 1) 
Exclusion Criteria 
1. Patients who are candidates for surgical resection 
2. Patients with lesion < 2 cm 
3. Patients who have contraindication to receive either TACE or proton 
4. Patients with serum alpha fetoprotein > 500 
5. Patients with metastasis or macrovascular invasion 
6. Patients treated previously for HCC by any locoregional treatment 
7. Patients with prior liver transplant 
8. Patients with Child class C 
9. Patients with MELD score of > 25 (Appendix 5) 
10. Patients with other comorbid diseases that may impact survival 
11. Patients with ongoing alcohol intake 
12. Patients with active sepsis 
13. Patients with gastrointestinal bleeding within a week 
14. Patients unwilling to sign informed consent form 
15. Patients with history of noncompliance 
 
 
Methods 
 
Patients meeting the inclusion and exclusion criteria will be randomized (1:1) by an 
individual who is not a study investigator using the random number method. 
Subjects will be registered and randomized by contacting Roger Grove (ext 44032, 
rgrove@dominion.llumc.edu).  Subjects will be randomly assigned to one of two 
groups: 
 
Group 1: patients will receive one or more sessions of TACE (Appendix 3). 
Group 2: patients will receive 15 consecutive sessions of proton beam radiation 
(Appendix 4).  
 
Primary Endpoint 
The primary end point of the study is to measure overall survival defined as the 
time from randomization until death. In order to control for non-cancer death related 
factors that may compound the survival rate, a competing risk analysis rather than 
Kaplan-Meier will be used to compare the survival between the two groups. 
Secondary Endpoints 
1. Time to progression.   
This endpoint reflects the time between randomization and radiological 
progression as defined by the amendments of the Response Evaluation 
Criteria in Solid Tumors (RECIST) (16).   
A. Complete Response is defined as the disappearance of any 
intratumoral arterial enhancement in all target lesions. 

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B.  Partial Response is at least a 30% decrease in the sum of diameters 
of viable (contrast enhancement in the arterial phase) target lesions, 
taking as reference the baseline sum of the diameters of target 
lesions. 
C.  Progressive Disease is an increase of at least 20% in the sum 
diameters of viable (enhancing) target lesions, taking as reference the 
smallest sum of the diameters of viable (enhancing) target lesions 
recorded since the treatment started. Or the appearance of one or 
more new lesions.  
 
 
 
A newly detected hepatic nodule will be classified as HCC- and will be 
 
declared as evidence of progression- when its longest diameter is at 
 
least 10 mm and the nodule shows the typical vascular pattern of HCC 
 
on dynamic imaging.  Lesions larger than 10 mm that do not show a 
 
typical vascular pattern can be diagnosed as HCC by evidence of at 
 
least 1 cm interval growth in subsequent scans. 
 
D. Stable Disease is any cases that do not qualify for either partial 
response or progression disease. 
 
 
 
MRI or CT-scan of the abdomen will be used to determine the targeted 
lesions for treatment and its baseline measurements. Target lesions will 
be measured using a single linear summation of the large diameter of the 
tumor. The average of two measurements by two independent radiologists 
will be considered for baseline and follow up assessment.  
 
2.  
Downstaging 
 
This endpoint will be applied to subjects in whom their tumor burden exceed 
 
Milan criteria but meet San Francisco criteria (Appendix 1).  The direct 
 
measurement of the longest diameter of the viable tumor will be compared 
 
pre-and-post treatment.  Usually, patients with San Francisco criteria will not 
 
be qualified for MELD score exception upgrade on UNOS waiting list unless 
 
their tumor burden is down-staged to Milan criteria using one of the 
 
locoregional treatments. Measuring this endpoint will help in comparing the 
 
efficacy of proton versus TACE in downstaging tumor in patients who meet 
 
San Francisco criteria. 
 
Follow Up 
Patients with HCC usually require either CT scan or MRI of the abdomen to be 
performed routinely every three months to monitor tumor progression.  Patients 
undergoing any locoregional treatment usually require a CT scan or MRI of the 
abdomen to be performed 4-6 weeks after the treatment and then every three 
months.  Follow up imaging will be the same modality used at baseline (CT or MRI). 
Patients are usually evaluated in the liver clinic 4 weeks after treatment and then 
every three months.  Subjects receiving proton therapy will also be followed in 
radiation medicine clinic by their treating radiation oncologist every 3 months for the 
first year then every 6 months.  Participants in this study will be followed according 
to this protocol.  No radiological testing will be ordered for the purpose of the study 
as the recommended assessments follow the current standard of care.  Patients will 
be followed for research purposes until death or transplant, or until which time the 
study investigators determine the study is complete. 

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Data and Statistics 
Data will be evaluated according to intent to treat analysis.  One- and two-year 
survival will be compared between two groups using competing risk analysis.  This 
analysis will provide an estimate of HCC-related death in the presence of alternate 
yet plausible outcomes such as death from liver failure or liver transplantation.  It is 
also a better technique in illustrating differential rates of competing outcomes in 
patients waiting for liver transplantation.  This analysis will limit the effects of 
confounding factors such as death from liver disease.  Secondary end points will be 
compared using Student’s t-test for quantitative data and chi-squared (χ2) test or 
Fisher’s exact test for qualitative data. Demographics and standard of care 
laboratory data between groups will be compared. Logistic regression will be used to 
determine independent factors affecting survival.  
 
The study is designed and powered to show at least 15% difference in mortality 
between two groups. Group size is calculated by assuming that patients in the TACE 
group will have at least 15% improvement in 2-year survival compared to the proton 
beam group. With 110 patients in each group the study has 80% power to detect a 
15% difference in the mortality between two groups. We are not expecting any 
significant drop out because both treatments are considered crucial for patients’ 
survival; and also based on our experience in treating these patients for many years 
at LLUMC.  The level of significance is 0.05 (2-sided) for all statistical tests. The 
Statistical Package for the Social Sciences (SPSS 16.0 for window; SPSS, Inc., 
Chicago, Illinois) was used for all statistical analyses.   
 
We will conduct an interim analysis after randomizing 40 patients in each group.  
This analysis will determine if there is any early significant difference in survival 
between two groups.  The interim report will be submitted to the Institutional Review 
Board.   
 
Data will be collected anonymously and subjects will be identified using a numerical 
code.  The code will be stored at the PI and Co-PI office.  The study database will be 
maintained and stored in the department of radiation medicine.  Only PI, CO-PI and 
research coordinators will have access to the data.  
 
Budget 
This study will utilize all the routine radiological and biochemical tests that are part 
of the medical care of these patients.  There will be no specific blood or radiological 
testing that will be performed or ordered only for the purpose of the study.  TACE is 
considered a standard of care for HCC patients and all insurance companies including 
MediCal and Medicare pay for this treatment. Many insurers will cover proton 
treatment for HCC This study does not incur any extra expenses that require 
additional funding. 
 
Appendix 1 
 

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Tumor Classification 
Milan Criteria 
Solitary lesion ≤ 5 cm or  3 lesions, none of > 3 cm 
 
San Francisco Criteria 
Solitary lesion ≤ 6.5 cm or ≤ 3 lesions none > 4.5 cm and total tumor diameter ≤ 8 
cm 
 

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Appendix 2 
 
Child-Pugh-Turcotte Score and Class 
 
1.  Bilirubin (mg/dl) 
 
<2    OR < 4 for patients with primary biliary cirrhosis    (1 point) 
2-3 
OR 4-10 for patients with primary biliary cirrhosis  (2 points) 
>3    OR > 10 for patients with primary biliary cirrhosis  (3 points) 
 
2. Albumin (g/dl) 
 
>3.5      (1 point) 
 
3.5-2.8  (2 points) 
 
<2.8      (3 points) 
 
3.  PT prolongation (INR) 
 
<4 seconds (<1.7)        (1 point) 
 
4-6 seconds (1.7-2.3)   (2 points) 
 
>6 seconds (>2.3)        (3 points) 
 
 
4. Ascites 
 
Absent       
 
(1 point) 
 
Slight          
 
(2 points) 
 
Moderate   
 
(3 points) 
 
5. Encephalopathy 
 
Absent              
(1 point) 
 
Mild (I-II)          
(2 points) 
 
Severe (III-IV)   
(3 points) 
 
Class Interpretation: 
Class A: 5-6 
Class B: 7-9 
Class C: 10-15 
 
Stages of Hepatic Encephalopathy 
    Stage 1: Euphoria or depression, mild confusion, slurred speed, disordered sleep 
    Stage 2: Lethargy, moderate confusion 
    Stage 3: Marked confusion, incoherent speech, sleeping but arousable 
    Stage 4: Coma, initially responsive to noxious stimuli, but later unresponsive 
 
 

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Appendix 3 
 
Transarterial Chemoembolization Treatment Protocol 
 
This procedure is done with the help of fluoroscopy (type of x-ray) imaging. A 
catheter (long, narrow tube) is inserted into the femoral artery in the groin and is 
threaded into the aorta (the main artery of the body). From the aorta, the catheter 
is advanced into the hepatic artery. Once the branches of the hepatic artery that 
feed the liver cancer are identified, the chemotherapy is infused and the arterial 
branch that supply the tumor is embolized using Gel Foam or Lipoid. The whole 
procedure takes one to two hours, and then the catheter is removed. 
The patient generally stays in the hospital overnight for observation. A sandbag is 
placed over the groin to compress the area where the catheter was inserted into 
the femoral artery. The nurses periodically check for signs of bleeding from the 
femoral artery puncture. They also check for the pulse in the foot on the side of the 
catheter insertion to be sure that the femoral artery is not blocked as a result of 
the procedure. (Blockage would be signaled by the absence of a pulse). 
Generally, the liver tests increase (get worse) during the two to three days after 
the procedure. This worsening of the liver tests is actually due to death of the 
tumor (and some non-tumor) cells. The patient may experience some post-
procedure abdominal pain and low-grade fever. However, severe abdominal pain 
and vomiting suggest that a more serious complication has developed. Imaging 
studies of the liver are repeated in six to 12 weeks to assess the size of the tumor 
in response to the treatment.  
 
 
 
 
 
 
 

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Appendix 4 
 
Proton Beam Radiotherapy Treatment Protocol 
 
Procedures for HCC subjects randomized to proton therapy: 
 
 
Immobilization and Treatment planning CT Scan 
 
Immobilization 
 
All patients will be fit with a full-body immobilization device to limit day-to-day set 
up variations and to reduce interfraction alignment errors.  This will be accomplished 
by placing the subject supine within a half cylinder PVC shell then adding two-part 
foam to create a rigid mold.  This device will be used for all subsequent patient 
treatments to provide reproducible patient alignment. 
 
Treatment Planning CT 
 
Subjects will undergo CT simulation in the department of radiation medicine while 
lying in their immobilization device.  All images will be acquired with IV contrast 
enhancement during the arterial phase.  Image acquisition will take place only when 
the subject is actively breath holding at end-expiration.  Imaging will cover the entire 
abdomen from above the right hemi-diaphragm through the 5th lumbar vertebral 
body.  Recommended scan spacing is 3x2 mm. 
 
Target Volume and Normal Tissue Definition 
 
Gross Tumor Volume (GTV) – The GTV will be contoured on each CT image and will 
include all areas of known disease as identified on the planning images and/or seen 
on diagnostic CT or MRI.   
 
Clinical Target Volume (CTV) – A CTV will be created to extend 1cm beyond the GTV 
in all dimensions.  This volume may be edited if it extends beyond the liver 
parenchyma.  The CTV will be edited so that it will not include organs known not to 
be involved by the tumor (i.e. abdominal wall, kidney, bowel). 
 
Normal Tissue Definition – All organs and normal tissue regions not targeted for 
treatment will be contoured for dose-volume-histogram calculations.  The entire liver 
will be contoured in all cases taking care to omit the gallbladder and portal vessels.  
Bowel that lies near the target volume and the right kidney should also be routinely 
contoured.  
 
  
 
3-Dimensional Treatment Planning, Dose Definitions, and Normal Tissue Constraints 
 
 
Treatment Planning 
 

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A computerized 3-Dimensional treatment plan will be generated utilizing the Odyssey 
treatment planning system at LLUMC.  The target region will be the CTV with the 
additional margin to account for daily setup variations and energy specific beam 
penumbra.   Beam angles typically used include right lateral, posterior, and posterior 
oblique beams.   
Anterior beams should be used only in selected patients, as these beams will not be 
within the immobilization device.  Beam weighting and custom editing of beams 
shaping devices may be utilized to optimize the final dose distribution.  All computer 
simulated treatment plans require approval by the treating physician prior to patient 
treatment. 
 
 
Proton Dose to CTV 
 
All doses will be prescribed to a point at or near the center of the CTV target region.  
The total dose delivered will be 70.2 CGE given in 15 fractions over a three-week 
course.  The uniformity of dose across the target region will not vary by more than 
10% of the prescribed dose.  At least two beams will be treated each day to reduce 
the dose at the beam entry site.   
 
 
Normal Tissue Constrains 
 
Liver – Dose constraints for the liver will be based on dose-volume histogram (DVH) 
analysis from the Odessey treatment planning system.  The dose that falls within the 
GTV will be excluded from the DVH calculation; however dose given to liver tissues 
outside the GTV but within the CTV will be included.  The treatment-planning goal 
will be to limit the volume of liver receiving more then 30 Gy to 33% or less.  If this 
constraint cannot be met, the additional CTV margin may be changed from 1cm to 
5mm.  This will be considered a minor protocol violation and will be noted in the 
patient record for future analysis.   
 
Bowel – If any portion of the bowel falls within the 90% isodose volume field 
reductions will be required.  Full margins will used for the first seven fractions of 
treatment.  The following 8 fractions will be delivered with modifications that limit 
dose to the bowel surface to 50% of the remaining dose.  In these cases the 
minimum dose to the CTV and GTV will be recorded for future analysis. 
 
Kidney – At least 50% of the right kidney will receive no more then 20 Gy.  This 
constrain assumes complete sparing of the left kidney. 
 
Treatment Delivery 
 
Patients will be treated at the proton treatment center at LLUMC.  For each 
treatment, the patient will be placed in their custom-made immobilization device.  
Orthogonal diagnostic x-ray images will be taken of the treatment area and 
registered with the digitally reconstructed radiographs created from the planning CT 
scan.  All misalignments greater then 1mm from the established treatment isocenter 
will be corrected.  All beam shaping devices will be verified each day both by the 
therapy personnel and with the record and verify system.  The initial treatment setup 
and subsequent new treatment fields will be verified by a physician prior to that 
day’s treatment.  At least two fields will be treated daily.  Treatment will only be 
given during an active breath hold at end-expiration to minimize respiratory motion 
of the liver.  Fifteen fractions over 3 weeks will be delivered.  All patients will be 

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clinically evaluated, weekly, by the treatment radiation oncologist to assess 
treatment tolerance and to monitor for acute toxicities.       
 
 
 
 
 

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Appendix 5 
 
Model For End-Stage Liver Disease (MELD) Score 
The MELD score is calculated using the following equation: 
3.8 x log (e) (bilirubin mg/dL) + 11.2 x log (e) (INR) + 9.6 log (e) 
(creatinine mg/dL) 
The equation seeks to calculate a patient’s likelihood of dying within three months 
from their liver disease. It is used by UNOS to allocate organ for liver transplant for 
patient on the list.  Scores range from 6-40.  A score of six indicates the least ill 
patient and a score of forty indicates the sickest patient.  The priority for organ 
allocation is given for patients with the highest MELD score. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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