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Liver Transplantation Workup

  • Author: Cosme Manzarbeitia, MD, FACS; Chief Editor: Julian Katz, MD  more...
 
Updated: Oct 02, 2015
 

Laboratory Studies

These 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:

  • Liver function tests, total protein, albumin
  • Hepatitis screen (A, B, C)
  • Serologies - Cytomegalovirus (CMV), herpes simplex virus (HSV), Epstein-Barr virus (EBV), HIV
  • Tumor markers
  • Alpha-fetoprotein, cholinesterase
  • Arterial blood gases
  • Others (selective) - Carbohydrate antigen 19-9, cancer antigen 125

Evaluation and workup of prospective liver transplant recipients is as follows: The first step in the process of evaluating a potential candidate for LT is to determine the severity of the liver disease by clinical evaluation. In addition, an objective assessment, to include a comprehensive laboratory and radiological evaluation, is undertaken. The goal of this evaluation is 3-fold. First, it must establish a diagnosis of ESLD; second, it must exclude any absolute or relative contraindication to the proposed procedure; finally, it must assess the suitability and degree of illness of each patient to better allocate resources and optimize survival. 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:

  • Cardiopulmonary clearance
  • Psychiatrist and social worker consultations
  • Financial clearance
  • Nephrologist, infectious diseases specialist, or dentist, as needed

One of the most important tools in this scheme is the Child-Turcotte-Pugh (CTP) scoring system, which is the system most widely used to grade the severity of liver disease. A patient is considered to be Child class A if he or she has fewer than 7 points, Child class B if he or she has 7-9 points, and Child class C if he or she has more than 10 points. For listing purposes, a patient must have at least 7 points (ie, be at least a Child class B), according to the minimal listing criteria consensus initially developed when the CTP score was the basis for organ allocation. Today, the CTP score is no longer the basis for organ allocation because this is now based on the Model for End-Stage Liver Disease (MELD) scoring system (see below; also see the MELD Score calculator).

Table. CTP Scoring System for Assessment of Severity of Disease (with respect to listing) (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

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. Thus, recent developments in the allocation system are investigating the MELD scoring system as the new basis for organ allocation.

Because of the many factors (ie, increasing number of deaths while on liver waiting list, inability to accurately categorize liver patients according to severity of liver disease using the partially subjective CTP classification, reports suggesting that waiting time correlates poorly with death while on the waiting list), a consensus opinion emerged that a revised allocation scheme was needed. The new 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 MELD and Pediatric End-Stage Liver Disease (PELD) survival models for all patients with chronic liver disease.

The MELD score is based on 3 biochemical variables, (1) serum bilirubin, (2) serum creatinine, and (3) international normalized ratio, and has been shown in retrospective and prospective studies to be highly predictive of 3-month mortality in patients with chronic liver disease. Similarly, the PELD model for pediatric patients (see below; also see the PELD Score calculator) was developed based on analyses 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:

  • Serum creatinine (Log e value) 0.957
    • The maximum serum creatinine considered within the MELD score equation is 4.0 mg/dL (ie, for candidates with a serum creatinine >4.0 mg/dL, the serum creatinine level is set to 4.0 mg/dL).
    • 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.
  • Serum bilirubin (Log e value) 0.378
  • International normalized ratio (INR) (Log e value) 1.120
  • Using these prognostic factors and regression coefficients, the UNetSM computerized system assigns a MELD score for each candidate based on the following calculation: MELD score = 0.957 x Log e (creatinine mg/dL) + 0. 378 x Log e (bilirubin mg/dL) + 1.120 x Log e (INR) + 0.643. Laboratory values < 1.0 are set to 1.0 for the purposes of the MELD score calculation. [2]
  • As an example, for a hypothetical candidate with cirrhosis caused by hepatitis C virus who has a serum creatinine concentration of 1.9 mg/dL, a serum bilirubin concentration of 4.2 mg/dL and an INR value of 1.2, the risk score would be calculated as follows: MELD score = (0.957 x Log e 1.9) + (0.378 x Log e 4.2) + (1.120 x Log e 1.2) + 0.643 = 2.0039.
  • The MELD score for each liver transplant candidate derived from this calculation is rounded to the tenth decimal place and then multiplied by 10. The hypothetical candidate in the example described above, therefore, would be assigned a risk score of 20. The MELD score is limited to a total of 40 points maximum.
  • Pediatric End-Stage Liver Disease (PELD) scoring system:
    • Albumin (Loge value) -0.687
    • Total bilirubin (Loge value) 0.480
    • INR (Loge value) 1.857
    • Growth failure (<-2 standard deviations [SD]) 0.667
    • Age (< 1 y) 0.436 (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.)
    • UNetSM assigns a PELD score for each candidate based on the following calculation: PELD score = 0.436 (age [< 1 y]) – 0.687 x Loge (albumin g/dL) + 0.480 x Loge (total bilirubin mg/dL) + 1.857 x Loge (INR) + 0.667 (growth failure [<-2 SD present]). Laboratory values < 1.0 are set to 1.0 for the purposes of the PELD score calculation.[2] Growth failure is calculated based on age and gender using the current CDC growth chart.
    • This is a much more precise method of ranking patients; therefore, patients most in need will be given the highest priority for donated livers, rather than simply allocating them to patients who have waited longer but who may be much more stable. The MELD policy replaced status 2A, 2B, and 3 with a continuous scale in February 2002 and is the current basis for liver allocation. Neither of these 2 scoring systems favors all patients, specifically patients with HCCs or exceptional cases.

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. This committee consists 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:
    • Does the patient need LT as therapy for his or her disease?
    • Have the indications and contraindications been properly assessed?
    • What is the surgical risk?
    • Is the patient's medical condition such that he or she will be able to tolerate the procedure and postoperative course?
    • 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.[8] 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.

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Imaging Studies

See the list below:

  • Radiography (including chest radiography)
  • Duplex ultrasonography
  • Angiogram/magnetic resonance angiography (selective)
  • Abdominal CT scanning
  • Cardiopulmonary evaluation
  • Stress thallium scanning, coronary angiography (as indicated)
  • 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 MRI (DWI) with regard to per-patient sensitivity, negative predictive value and per-lesion sensitivity.[9] The latter 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.

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Other Tests

See the list below:

  • Electrocardiography
  • Pulmonary function testing
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Diagnostic Procedures

See the list below:

  • During the workup of these patients, many tests may be ordered. Specific testing is performed on a case-by-case basis.
  • In the author's experience, 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 SBP) and for therapeutic intent (eg, alleviation of distention and hepatohydrothorax).
  • Many patients undergo a TIPS procedure while awaiting LT because of complications that warrant this approach. These conditions include esophageal or gastric variceal bleeding, refractory ascites, and hepatorenal syndrome (HRS).
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Histologic Findings

Discussion of all the histopathological findings of the various diseases that lead to ESLD is beyond the scope of this article. In general, they can be classified into 3 broad categories: cirrhosis and fibroticlike states, acute hepatic necrosis, and malignancies.

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Contributor Information and Disclosures
Author

Cosme Manzarbeitia, MD, FACS Associate Professor of Surgery, Jefferson Medical College of Thomas Jefferson University; Chief Hepatobiliary and Head Transplant Surgeon, Crozer-Keystone Healthcare System

Cosme Manzarbeitia, MD, FACS is a member of the following medical societies: American Association for the Study of Liver Diseases, Americas Hepato-Pancreato-Biliary Association, International Liver Transplantation Society, American College of Surgeons, American Society of Transplant Surgeons

Disclosure: Nothing to disclose.

Coauthor(s)

Antonios Arvelakis, MD Assistant Professor of Surgery, Director, Kidney Paired Donation Program, Yale New Haven Transplantation Center, Yale University School of Medicine

Antonios Arvelakis, MD is a member of the following medical societies: American Society of Transplant Surgeons, American Society of Transplantation, Americas Hepato-Pancreato-Biliary Association, International Liver Transplantation Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Julian Katz, MD Clinical Professor of Medicine, Drexel University College of Medicine

Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law, Medicine & Ethics, American Trauma Society, Association of American Medical Colleges, Physicians for Social Responsibility

Disclosure: Nothing to disclose.

Additional Contributors

Tushar Patel, MB, ChB Professor of Medicine, Ohio State University Medical Center

Tushar Patel, MB, ChB is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association

Disclosure: Nothing to disclose.

Acknowledgements

Youmin Wu, MD Professor, Department of Surgery, Transplantation Division, University of Arkansas for Medical Sciences

Youmin Wu, MD is a member of the following medical societies: American Medical Association

Disclosure: Nothing to disclose.

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Frequency of liver transplantation based on diagnosis.
United Network for Organ Sharing regional map.
Timing of liver transplantation.
Challenges and controversies of liver transplantation.
Organ allocation and transplantation.
Retractors in place aid exposure in this case of polycystic liver disease with a very large liver.
Hilar dissection begins with exposure of the undersurface of the liver.
Venous bypass.
Upper caval anastomosis.
Lower caval anastomosis.
Piggyback dissection.
Liver resection.
Living-related donor liver after splitting.
Split liver.
Common adverse effects of immunosuppression.
Etiologies of posttransplant liver dysfunction.
Workup of posttransplant allograft dysfunction.
Relative mortality rates (transplant vs waitlist) by MELD.
Table. CTP Scoring System for Assessment of Severity of Disease (with respect to listing)
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
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