Approach Considerations
The workup of a potential candidate for liver transplantation (LT) determines the patient's degree of illness and overall suitability for LT. This ensures better allocation of resources and optimizes survival. The first step is to establish a diagnosis of end-stage liver disease (ESLD) by clinical evaluation; the second is to exclude any absolute or relative contraindication to LT.
The specific tests are outlined below. Once the results are received, specific consultations are sought to clear the patient for LT.
Mandatory consultations and clearances are as follows:
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Cardiopulmonary clearance
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Psychiatrist and social worker consultations
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Financial clearance
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Nephrologist, infectious diseases specialist, or dentist, as needed
The liver allocation system implemented by the Organ Procurement Transplantation Network in February 2002 is based primarily on the severity of liver disease as assessed by the Model for End-Stage Liver Disease (MELD) and Pediatric End-Stage Liver Disease (PELD) survival models for all patients with chronic liver disease.
The MELD score, which is based on biochemical variables (see below; also see the MELD Score calculator), has been shown in retrospective and prospective studies to be highly predictive of 3-month mortality in patients with chronic liver disease. The PELD model for pediatric patients, which incorporates both clinical and biochemical variables (see below; also see the PELD Score calculator) was developed through analysis of data from the Study of Pediatric Liver Transplantation database and has been shown retrospectively to be predictive of waiting list mortality in pediatric patients.
Model for End-Stage Liver Disease (MELD) scoring system
The MELD score is calculated on the basis of the following variables:
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Serum creatinine
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Serum bilirubin
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International normalized ratio (INR)
For candidates on dialysis, defined as having 2 or more dialysis treatments within the prior week, or candidates who have received 24 hours of continuous venovenous hemodialysis (CVVHD) within the prior week, the serum creatinine level is automatically be set to 4.0 mg/dL.
Using these prognostic factors and regression coefficients, the UNetSM computerized system assigns a MELD score for each candidate based on the following calculation:
MELDScore = 10 * ((0.957 * ln(Creatinine)) + (0.378 * ln(Bilirubin)) + (1.12 * ln(INR))) + 6.43 [7]
The MELD score is limited to a total of 40 points maximum.
Pediatric End-Stage Liver Disease (PELD) scoring system
The PELD score is calculated on the basis of the following variables:
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Age
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Weight
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Height
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Albumin
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Total bilirubin
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INR
Scores for candidates listed for liver transplantation before the candidate’s first birthday continue to include the value assigned for age (< 1 y) until the candidate reaches 24 months of age.
Using these prognostic factors and regression coefficients, the UNetSM computerized system assigns a score for each candidate based on the following calculation:
PELDScore = 10 * ((0.480 * ln(Bilirubin)) + (1.857 * ln(INR)) - (0.687 * ln(Albumin)) + ListingAgeFactor + Growth) [7]
The Growth term in the equation is set to 0.667 when the subject's height or weight is less than 2 standard deviations below the mean values for that age. Thus, the presence of growth failure contributes almost 7 points to the PELD score.
UNOS specifies urea cycle disorders, organic acidemia, and hepatoblastoma as exceptions to the PELD score calculation (and MELD score in patients age 12 to 17 years). For patients with these diseases, the PELD score is set at 30. Other metabolic diseases may be considered for exception scores by direct petition to UNOS.
Listing of candidates
Once the workup is complete, the patient and all workup results are presented to the candidate selection committee for a decision about the suitability for transplantation. These committees consist of transplantation surgeons, hepatologists, psychiatrists, social work representatives, cardiologists, pulmonologists, anesthesiologists, and, occasionally, the patient's primary care physician.
The following questions are posed to the committee before listing the patient for transplantation:
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Does the patient need LT as therapy for his or her disease?
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Have the indications and contraindications been properly assessed?
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What is the surgical risk?
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Is the patient's medical condition such that he or she will be able to tolerate the procedure and postoperative course?
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What are the chances of recurrent disease affecting graft and patient survival?
Volk et al found that the structure of committee meetings varies by center; however, the process is uniform and primarily involves inductive reasoning to review suitability for transplantation. [24] In their observations, patients were excluded if they were too well, too sick, or too old or had nonhepatic comorbid conditions, substance abuse problems, or other psychosocial barriers.
Laboratory Studies
Laboratory studies in potential LT candidates are oriented toward determining the etiology of the disease, excluding HIV and other infections that may compromise a successful LT, and screening for the presence of tumors. The following laboratory tests are those most commonly ordered during a LT evaluation:
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Liver function tests, total protein, albumin
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Hepatitis screen (A, B, C)
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Serologies - Cytomegalovirus (CMV), herpes simplex virus (HSV), Epstein-Barr virus (EBV), HIV
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Tumor markers
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Alpha-fetoprotein, cholinesterase
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Arterial blood gases
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Others (selective) - Carbohydrate antigen 19-9, cancer antigen 125
Imaging Studies
The following imaging studies may be performed in select cases to determine the etiology of the liver disease:
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Radiography (including chest radiography)
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Duplex ultrasonography
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Angiogram/magnetic resonance angiography (selective)
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Abdominal computed tomography (CT) scanning
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Cardiopulmonary evaluation
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Stress thallium scanning, coronary angiography (as indicated)
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Echocardiography
In a study comparing the performance of imaging techniques for the detection of hepatocellular carcinoma in pre-liver transplant patients with cirrhosis, contrast-enhanced T1-weighted imaging (CE T1WI) outperformed diffusion-weighted magnetic resonance imaging (DWI) with regard to per-patient sensitivity, negative predictive value, and per-lesion sensitivity. [25] The last difference, however, was significant only for lesions between 1 and 2 cm, suggesting that DWI is a reasonable alternative to CE T1WI for detection of hepatocellular lesions above 2 cm.
Diagnostic Procedures
During the workup of LT candidates, specific testing is performed on a case-by-case basis. Most patients undergo both upper and lower GI endoscopies to evaluate for the presence of esophageal or gastric varices or to exclude GI malignancy.
Other common procedures may include paracentesis in patients with ascites, both for diagnostic purposes (eg, to exclude spontaneous bacterial peritonitis) and for therapeutic intent (eg, alleviation of distention and hepatohydrothorax). Many patients undergo transjugular intrahepatic portosystemic shunting (TIPS) while awaiting LT because of complications that warrant this approach, such as the following:
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Esophageal or gastric variceal bleeding
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Refractory ascites
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Hepatorenal syndrome (HRS)
Histologic Findings
Discussion of all the histopathological findings of the various diseases that lead to end-stage liver disease is beyond the scope of this article. In general, they can be classified into 3 broad categories:
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Cirrhosis and fibroticlike states
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Acute hepatic necrosis
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Malignancies
Staging
The Child-Turcotte-Pugh (CTP) scoring system is widely used to grade the severity of liver disease. See the table below.
Table. Child-Turcotte-Pugh Scoring System for Assessment of Severity of Disease (Open Table in a new window)
Parameter |
1 Point |
2 Points |
3 Points |
Encephalopathy |
None |
Grade 1-2 |
Grade 3-4 |
Ascites |
None |
Medically controlled |
Uncontrolled |
Albumin, g/dL |
>3.5 |
2.8-3.5 |
< 2.8 |
Bilirubin, mg/dL |
< 2 |
2-3 |
> 3 |
International normalized ratio |
< 1.7 |
1.7-2.3 |
>2.3 |
CTP classification is as follows:
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Child class A: < 7 points
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Child class B: 7-9 points
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Child class C: ≥10 points
However, the CTP score is no longer the basis for organ allocation. Although a good effort to grade severity of disease, this classification does not reflect the severity of disease in persons with cholestatic diseases, such as primary biliary cirrhosis or primary sclerosing cholangitis (PSC), because the bilirubin limits are significantly higher for these conditions and the other manifestations are not present until very late in the disease.
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Frequency of liver transplantation based on diagnosis.
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United Network for Organ Sharing regional map.
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Timing of liver transplantation.
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Challenges and controversies of liver transplantation.
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Organ allocation and transplantation.
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Liver transplantation. Retractors in place aid exposure in this case of polycystic liver disease with a very large liver.
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Liver transplantation. Hilar dissection begins with exposure of the undersurface of the liver.
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Liver transplantation. Venous bypass.
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Liver transplantation. Upper caval anastomosis.
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Liver transplantation. Lower caval anastomosis.
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Liver transplantation. Piggyback dissection.
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Liver transplantation. Liver resection.
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Liver transplantation. Living-related donor liver after splitting.
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Liver transplantation. Split liver.
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Common adverse effects of immunosuppression.
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Liver transplantation. Etiologies of posttransplant liver dysfunction.
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Workup of posttransplant allograft dysfunction.
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Liver transplantation. Relative mortality rates (transplant vs waitlist) by MELD.
Tables
Parameter |
1 Point |
2 Points |
3 Points |
Encephalopathy |
None |
Grade 1-2 |
Grade 3-4 |
Ascites |
None |
Medically controlled |
Uncontrolled |
Albumin, g/dL |
>3.5 |
2.8-3.5 |
< 2.8 |
Bilirubin, mg/dL |
< 2 |
2-3 |
> 3 |
International normalized ratio |
< 1.7 |
1.7-2.3 |
>2.3 |
