Guidelines for the evaluation of liver transplantation (LT) were published by the American Association for the Study of Liver Diseases (AASLD) in 2005. To date, significant advances have been made in the treatment of chronic liver disease, particularly in the antiviral treatment of chronic viral hepatitis. Nonalcoholic fatty liver disease is of increasing interest as an etiology leading to cirrhosis and hepatocellular carcinoma requiring liver transplantation for treatment.
In addition, indications for individual diseases such as hepatocellular carcinoma have been standardized for LT, and specific guidelines exist for chronic viral hepatitis. Evaluating this complex group with a variety of midlife specific comorbidities requires a multidisciplinary approach, and the 2013 updated guidelines reflect this need with recommendations that have evolved to assist in their management of heart disease, approved by the American Association for the Study of Liver Diseases and the American Society for Transplantation, representing the joint opinion of both societies. As LT long-term survivors become more numerous, their quality of life and the coexisting factors that affect longevity are of greater concern. The purpose of this guideline is to provide evidence-based medical evidence for the evaluation of potential adult liver transplant candidates for transplantation.
To more fully describe the available evidence to support the recommendations, the American Association for the Study of Liver Diseases Practice Guidelines Committee has adopted an improved Classification of Assessment, Development and Evaluation Recommendations Grading Task Force. Both the classification and recommendations are based on three categories: Levels of Evidence Source I through III; quality of evidence classified as high (A), moderate (B), and low quality (C); and strength of recommendation classified as strong (l) and weak (2). The recommendations are as follows.
I. Indications for liver transplantation
Severe acute or advanced chronic liver disease that has reached the limit of medical treatment and is suitable for liver transplantation: (l) acute liver failure; (2) complications of cirrhosis: ascites, chronic gastrointestinal blood loss due to portal hypertensive gastropathy, hepatic encephalopathy, hepatocellular carcinoma, refractory variceal bleeding, synthetic dysfunction; (3) hepatic metabolic disorders with systemic manifestations: α1-antitrypsin deficiency, familial amyloidosis (3) systemic manifestations of hepatic metabolic disorders: α1-antitrypsin deficiency, familial amyloidosis, glycogen storage disease, hemochromatosis, primary oxaluria, Wilson’s disease; (4) systemic complications of chronic liver disease: hepatopulmonary syndrome, portal pulmonary hypertension.
Recommendation 1: Patients with cirrhosis should be considered for liver transplantation evaluation (1-A) once they develop one of the following complications, such as ascites, hepatic encephalopathy, ruptured esophageal variceal bleeding, or hepatocellular dysfunction leading to end-stage liver disease (MELD) score ≥ 15; Recommendation 2: In the waiting population for liver transplantation, etiologic treatment should be done whenever possible to manage complications of liver failure, such as ascites, hepatic encephalopathy or ruptured variceal bleeding (l-B); Recommendation 3: Potential liver transplant candidates presenting with worsening renal insufficiency or other evidence of rapid liver failure should be promptly evaluated for liver transplantation (2-B).
II. Transplant Evaluation Process
While the severity of liver disease is the initial point of concern in initiating liver transplant evaluation, there are a large number of other important factors to consider. Contraindications to liver transplantation: MELD score < 15, severe cardiopulmonary disease, acquired immunodeficiency syndrome, uninterrupted alcohol or illicit drug abuse, metastatic spreading hepatocellular carcinoma, uncontrolled sepsis, intrahepatic cholangiocarcinoma with anatomic abnormalities that preclude liver transplantation, extrahepatic malignancy, fulminant liver failure, sustained intracranial pressure > 50 mmHg or cerebral perfusion pressure < 40 mmHg, angiosarcoma Chronic noncompliance and lack of adequate social support system.
III. Medical comorbidities including obesity, geriatric and cardiac disease
Obesity: Recommendation 4: Obese patients (WH0 level 1 or higher) require dietary counseling prior to liver transplantation (1-C). Recommendation 5: Grade 3 obesity [body mass index (BMI) ≥ 40] is a relative contraindication to liver transplantation (2-B).
2. Coronary artery disease: Recommendation 6: Cardiac function assessment needs to include stress echocardiography as an initial screening test and cardiac catheterization intervention for those indicated to assess cardiac risk factors (1-B). Recommendation 7: Liver transplant candidates with significant pre-transplant coronary stenosis should be considered for revascularization (2-C).
3. Age: Recommendation 8: In the absence of significant comorbidities, elderly recipients (age >70 years) are not a contraindication to liver transplantation (2-B).
IV. Pulmonary Hypertension
Recommendation 9: Liver transplant candidates should be excluded from portal pulmonary hypertension (POPH) by routine echocardiography. A right ventricular systolic pressure ≥45 mmHg (1 mmHg=0.133kPa) is an indication for right heart catheterization (l-B). Recommendation 10: Potential recipients with POPH should be evaluated by a pulmonary or cardiologist for vasodilator therapy (l-A). Recommendation II: Potential recipients with POPH who respond to pharmacologic therapy and have a mean pulmonary artery pressure (MPAP) ≤35 mmHg may undergo liver transplantation (l-B).
V. Hepatopulmonary syndrome
Recommendation 12: Hepatopulmonary syndrome is more common in patients evaluated for liver transplantation and should be screened by quantitative pulse oximetry (1-A). Recommendation 13: The presence of severe hepatopulmonary syndrome increases morbidity and mortality, and such patients should be expedited for liver transplant evaluation (1-B).
VI. Renal insufficiency
Recommendation 14: Renal insufficiency requires adequate evaluation prior to liver transplantation to determine etiology and prognosis (l-A). Recommendation 15: Renal failure in liver transplant candidates, including chronic kidney disease with GFR <30 ml/min, acute kidney injury on dialysis for more than 8 weeks, or the presence of extensive glomerulosclerosis, is an indication for combined liver and kidney transplantation (l-B).
VII. Smoking
Recommendation 16: Smoking should be prohibited in liver transplant candidates (1-A).
VIII. Extrahepatic malignancy
Recommendation 17: Liver transplant candidates with extrahepatic malignancies should be thoroughly treated to achieve adequate tumor-free survival before entering the transplant queue (1-B); Recommendation 18: Candidates should be screened for age-appropriate cancer risk factors, e.g., colonoscopy, mammogram, official neck exfoliative cell smear (l-A).
IX. Infectious Diseases
Recommendation 19: Liver transplant candidates should be screened for bacterial, viral, and fungal infections prior to liver transplantation (l-A). Recommendation 20: Treatment for latent tuberculosis should be initiated prior to liver transplantation (l-B). Recommendation 1: Vaccination against pneumococcal, influenza, pertussis, diphtheria, and tetanus should be encouraged (l-A). Recommendation 22: If live vaccinations (mumps, measles, rubella, and varicella) are needed, they should be administered early in the evaluation process (l-B).
X. Nutrition
Recommendation 23: A nutritional assessment should be completed for each liver transplant candidate (1A).
XI. Bone Disease
Recommendation 24: Bone densitometry should be performed as part of the transplant evaluation and treatment for osteoporosis should be initiated prior to liver transplantation (1-A).
XII. HIV Infection
Recommendation 25: Patients with HIV infection may be candidates for liver transplantation if immune function is adequate and the virus is expected to be undetectable at the time of liver transplantation (l-A).
XIII. Psychosocial Assessment
Recommendation 26: Patient compliance with medical instructions and mental health stability (psychosocial) should be assessed and brought up to appropriate expectations (l-A). Recommendation 27: For methadone-maintained patients, liver transplantation should not be denied because of methadone use, and reduction or cessation of methadone should not be a requirement for entering the transplantation queue (l-B). Recommendation 28: Patients should have adequate social/caregiver support to provide necessary assistance between the time they enter the waiting list and the time they do not regain independent function postoperatively (l-B).
XIV. Special disease indications for liver transplantation
1. Hepatitis C: Recommendation 29: HCV infection is an indication for liver transplantation as is cirrhosis from other etiologies (l-A). Recommendation 30: Antiviral therapy should be considered prior to liver transplantation to reduce the risk of HCV recurrence after liver transplantation (l-B).
2. hepatitis B: recommendation 31: patients with HBV infection-related liver disease should receive antiviral therapy to suppress HBV replication prior to transplantation, along with continued surveillance for liver cancer (1-A).
3. autoimmune hepatitis: Recommendation 32: liver transplantation should be considered in patients with autoimmune hepatitis in the decompensated phase who do not respond to medical therapy or are candidates for medical therapy (I-A). Recommendation 33: Autoimmune hepatitis presenting with acute liver failure from which recovery is unlikely is an indication for liver transplantation (L-B).
4. primary biliary cirrhosis: Recommendation 34: primary biliary cirrhosis in the decompensated phase is an indication for liver transplantation (I-A). Recommendation 35: Severe pruritus, for which medical treatment is not effective, may also be an indication for liver transplantation (I-B).
5. Primary sclerosing cholangitis: Recommendation 36: Liver transplantation is an effective therapy for decompensated liver disease due to primary sclerosing cholangitis, including recurrent episodes of cholangitis and sepsis (I-A). Recommendation 37: Due to the high incidence of colon cancer in patients with primary sclerosing cholangitis and inflammatory bowel disease, annual colonoscopy should be performed both before and after transplantation (II-I 3).
6. Alcoholic liver disease: Recommendation 38: Patients with alcoholic liver disease evaluated for liver transplantation should have an early consultation for psychosocial assessment and development of addiction treatment goals (1-A). Recommendation 39: Given the long-term nature of alcohol dependence, ongoing supervision is an important component of a comprehensive treatment plan (l-B).
7. Acute Liver Failure: Recommendation 40: Patients with acute liver failure require immediate referral to a liver transplant center (1-A). Recommendation 41: Patients with acetaminophen overdose should be assessed for compliance with medical instructions, stability of mental health (psychosocial assessment), and meeting appropriate expectations (l-A).
8. Hepatocellular carcinoma: Recommendation 42: Liver transplantation is an effective treatment for liver cancer meeting the Milan criteria (l-A). Recommendation 43: Liver transplantation is a treatment option for hepatocellular carcinoma beyond the Milan criteria and downstaged to the Milan criteria (2-C).
9. Cholangiocarcinoma: Recommendation 44: Patients diagnosed with early-stage cholangiocarcinoma that cannot be surgically resected due to parenchymal disease or anatomic location may be considered for liver transplantation combined with neoadjuvant radiation therapy/pharmacologic therapy (lB). Recommendation 45: Patients with cholangiocarcinoma who are potential candidates for transplantation should consult a UNOS-approved center with an established oncologic evaluation and treatment program (IB) as soon as possible.
10. Metabolic diseases.
(l) NAFLD: Recommendation 46: Liver transplantation is an effective treatment for decompensated liver disease due to nonalcoholic steatohepatitis (NASH) or cryptogenic cirrhosis (I-A).
(2) α1- antitrypsin deficiency: Recommendation 47: decompensated cirrhosis due to al- antitrypsin deficiency is an indication for liver transplantation (I-A). Recommendation 48: Patients with alpha1- antitrypsin deficiency for transplantation evaluation should undergo pulmonary function tests and screening chest imaging tests to exclude pulmonary disease (I-A).
(3) Hereditary hemochromatosis: Recommendation 49: Cirrhotic decompensation due to hemochromatosis is an indication for liver transplantation (I-A). Recommendation 50: Transplant candidates with hemochromatosis should be treated with iron reduction prior to LT (I-B).
(4) Wilson disease: Recommendation 51: Acute liver failure in Wilson disease is an indication for emergency liver transplantation (I-A). Recommendation 52: Decompensated cirrhosis in Wilson disease unresponsive to drug therapy is an indication for liver transplantation (I-A). Recommendation 53: Liver transplantation is not recommended in Wilson’s disease encephalopathy because it is not effective in improving neurological prognosis (I-B).
(5) Hereditary amyloidosis: Recommendation 54: Familial amyloid polyneuropathy should be considered for LT as early as possible to reduce hepatic amyloid production early in the disease, especially before cardiac and ocular complications occur, as these complications do not improve effectively with LT (I-B).
(6) Primary hyperuricemia: Recommendation 55: Priority liver transplantation (before onset of progressive nephropathy) or combined liver-kidney transplantation in end-stage renal disease combinations can treat primary hyperuricemia and should be considered in patients who do not respond to drug therapy (I-A).
XV. MELD Exceptions
Recommendation 56: When liver transplant candidates’ MELD scores do not adequately reflect the severity of their liver disease, a MELD exception score (I-B) should be requested from the Regional Review Committee.