Guidelines for evaluating liver transplantation (LT) were published by the American Association for the Study of Liver Diseases (AASLD) in 2005. To date, significant progress has been made in the treatment of chronic liver disease, particularly antiviral therapy for chronic viral hepatitis. Non-alcoholic fatty liver disease (NAFLD) is of increasing interest as a cause of pathology leading to cirrhosis and hepatocellular carcinoma requiring liver transplantation therapy. In addition, indications for individual diseases of LT such as hepatocellular carcinoma have been standardized, and there are specific guidelines for chronic viral hepatitis. Evaluating this complex group with a variety of midlife-specific comorbidities requires a multidisciplinary approach, and the 2013 update of the guidelines reflects this need, with recommendations that have evolved to assist in the management of their cardiac disease, approved by the American Association for the Study of Liver Diseases and the American Society of Transplantation to represent the shared views of both societies. As the number of long-term LT survivors grows, 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 transplant evaluation of adult patients who are potential liver transplant candidates. In order to more fully characterize the available evidence in support of the recommendations, the American Association for the Study of Liver Diseases Practice Guidelines Committee has adopted the Improved Assessment, Formulation, and Evaluation of Recommendations Grading Workgroup Classification. Both the classification and the recommendations are based on three categories: source of evidence levels I through III; quality of evidence categorized as high (A), moderate (B), and low quality (C); and strength of recommendation categorized as strong (l) and weak (2). Its recommended suggestions are as follows. I. Indications for liver transplantation Severe acute or advanced chronic liver disease for which medical treatment has reached its limit 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 hemorrhage, and synthetic dysfunction; and (3) hepatic metabolic derangements with systemic manifestations: α1-antitrypsin deficiency , familial amyloidosis, glycogen storage disease, hemochromatosis, primary oxaluria, Wilson’s disease; (4) systemic complications of chronic liver disease: hepatopulmonary syndrome, portal hypertension. Recommendation 1: Patients with cirrhosis should be considered for liver transplantation evaluation once they develop one of the following complications, such as ascites, hepatic encephalopathy, ruptured esophageal varices with bleeding, or hepatocellular dysfunction resulting in an end-stage liver disease (MELD) score ≥15 (1-A). Recommendation 2: In people on the waiting list for liver transplantation, etiologic treatment should be done whenever possible to manage complications of hepatic dysfunction such as ascites, hepatic encephalopathy, or variceal rupture bleeding (L-B). Recommendation 3: Potential liver transplant candidates presenting with worsening renal insufficiency or other evidence of rapid hepatic decompensation should be rapidly evaluated for liver transplantation (2-B). II.THE TRANSPLANT EVALUATION PROCESS Although the severity of liver disease is the initial point of concern in initiating liver transplantation evaluation, there are a large number of other important factors that need to be considered. Contraindications to liver transplantation: a MELD score of <15, severe cardiopulmonary disease, acquired immunodeficiency syndrome, uninterrupted alcohol or prohibited substance abuse, metastatic spreading hepatocellular carcinoma, uncontrolled sepsis, intrahepatic cholangiocarcinoma with anatomical abnormalities not amenable to liver transplantation, extrahepatic malignancy, fulminant hepatic failure, sustained intracranial pressure of >50 mm Hg or cerebral perfusion pressure of < 40 mm Hg, hemangiosarcoma. Those who are chronically noncompliant and lack an adequate social support system. III Medical comorbidities including obesity, geriatric and cardiac disease 1. Obesity: recommendation 4: Obese patients (WH0 grade 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: Assessment of cardiac function needs to include a stress echocardiogram as a primary screening test, and cardiac catheterization interventions to assess cardiac risk factors if indicated (1-B). Recommendation 7:Revascularization should be considered in liver transplant candidates with significant pre-transplant coronary artery stenosis (2-C). 3. Age: Recommendation 8: Elderly recipients (age >70 years) are not a contraindication to liver transplantation in the absence of significant comorbidities (2-B). IV. Pulmonary hypertension Recommendation 9: Portopulmonary hypertension (POPH) should be excluded by routine echocardiography in the liver transplantation candidate pool. A right ventricular systolic pressure of ≥45 mmHg (1 mmHg = 0.133 kPa) is an indication to perform right heart cardiac catheterization for screening (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 prevalent in patients evaluated for liver transplantation and should be screened for by quantitative pulse oximetry (1-A). Recommendation 13: The presence of severe hepatopulmonary syndrome increases morbidity and mortality, and such patients should undergo expedited evaluation for liver transplantation (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 is an indication for combined liver and kidney transplantation in liver transplant candidates when it occurs, including chronic kidney disease with a GFR <30 ml/min, acute kidney injury with a dialysis duration of more than 8 weeks, or the presence of extensive glomerulosclerosis (l-B). VII.Smoking Recommendation 16: Smoking should be prohibited in liver transplant candidates (1-A). VIII. Extrahepatic malignancies Recommendation 17: Liver transplant candidates with extrahepatic malignancies should receive thorough treatment 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, mammography, and official cervical exfoliative cytology smear (l-A). IX Infectious Diseases Recommendation 19: Candidates for liver transplantation should be screened for bacterial, viral, and fungal infections prior to liver transplantation (l-A). Recommendation 20: Treatment of latent tuberculosis should be initiated prior to liver transplantation (l-B). Recommendation 21: Vaccination against pneumococcus, influenza, pertussis, diphtheria, and tetanus should be encouraged (l-A). Recommendation 22: If live vaccines (mumps, measles, rubella, and varicella) are required, 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 who are immunocompetent enough and in whom the virus is expected to be undetectable at the time of liver transplantation may be candidates for liver transplantation (l-A). XIII. Psychosocial Assessment Recommendation 26: Patients should be assessed for adherence to medical instructions and stability of their mental health (psychosocial) and be brought up to appropriate expectations (l-A). Recommendation 27: Liver transplantation should not be denied to methadone-maintained patients on the basis of methadone use, and reduction or cessation of methadone should not be a requirement for entry into the transplant waiting list (l-B). Recommendation 28: Patients should have adequate social/caregiver support to provide necessary assistance during the period between entering the waiting list and the time they have not regained independent functioning postoperatively (l-B). XIV. Special Disease Indications for Liver Transplantation 1. Hepatitis C: Recommendation 29: HCV infection is as much an indication for liver transplantation as cirrhosis from other etiologies (l-A). Recommendation 30: Antiviral therapy should be considered before liver transplantation to reduce the risk of HCV recurrence after liver transplantation (L-B). 2, Hepatitis B: Recommendation 31: Patients with liver disease associated with HBV infection should receive antiviral therapy to inhibit HBV replication prior to transplantation, while continuing to be monitored for hepatocellular carcinoma (1-A). 3. Autoimmune hepatitis: Recommendation 32: Liver transplantation should be considered in patients with autoimmune hepatitis in the decompensated stage who do not respond to medical therapy or are not candidates for medical therapy (I-A). Recommendation 33: Acute liver failure with unlikely recovery from autoimmune hepatitis 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, which is refractory to medical therapy, 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: Because of 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 undergoing evaluation for liver transplantation should be seen early for psychosocial assessment and development of addiction treatment goals (1-A). Recommendation 39: Considering the long-term nature of alcohol dependence, ongoing supervision is an important component of a comprehensive treatment program (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 adherence to medical instructions, stability of mental health (psychosocial assessment), and brought up to appropriate expectations (l-A). 8. Hepatocellular carcinoma: Recommendation 42: Liver transplantation is an effective treatment for hepatocellular carcinoma that meets the Milan criteria (l-A). Recommendation 43: Liver transplantation is a therapeutic option for hepatocellular carcinoma that exceeds the Milan criteria and downstages to the Milan criteria (2-C). 9. Cholangiocarcinoma: Recommendation 44: Liver transplantation combined with neoadjuvant radiation therapy/pharmacotherapy may be considered in patients diagnosed with early-stage cholangiocarcinoma that is not amenable to surgical resection due to parenchymal disease of the liver or anatomical location (lB). Recommendation 45: Patients with cholangiocarcinoma who are potential transplant candidates should consult a UNOS-approved center with an established oncologic evaluation and treatment protocol (IB) as soon as possible. 10. Metabolic Diseases: (l) Nonalcoholic Fatty Liver Disease: Recommendation 46: Liver transplantation is an effective treatment for decompensated liver disease resulting from nonalcoholic steatohepatitis (NASH) or cryptogenic cirrhosis (I-A). (2) α1-antitrypsin deficiency: recommendation 47: The decompensated phase of cirrhosis due to al-antitrypsin deficiency is an indication for liver transplantation (I-A). Recommendation 48: Patients with alpha1-antitrypsin deficiency evaluated for transplantation should undergo pulmonary function tests and screening with chest imaging to exclude lung disease (I-A). (3) Hereditary hemochromatosis: Recommendation 49: The decompensated phase of cirrhosis due to hemochromatosis is an indication for liver transplantation (I-A). Recommendation 50: Transplant candidates with hemochromatosis should undergo iron reduction therapy prior to LT (I-B). (4) Wilson's disease: recommendation 51: Acute liver failure in Wilson's disease is an indication for urgent liver transplantation (I-A). Recommendation 52: Decompensated cirrhosis in Wilson's disease that does not respond to pharmacologic therapy is an indication for liver transplantation (I-A). Recommendation 53: Liver transplantation is not recommended for Wilson disease encephalopathy because it is not effective in improving neurologic prognosis (I-B). (5) Hereditary amyloidosis: Recommendation 54: LT should be considered as early as possible in familial amyloid polyneuropathy to reduce hepatic amyloid production early in the course of the disease, especially before the development of cardiac and ocular complications, which do not effectively improve with LT (I-B). (6) Primary hyperuricemia: Recommendation 55: Priority liver transplantation (before the onset of progressive kidney disease) or liver-kidney co-transplantation for end-stage renal disease combinations can treat primary hyperuricemia and should be considered in patients who are not responding to pharmacologic therapy (I-A). XV. MELD EXCEPTION Recommendation 56: Regional review boards should be requested to grant a MELD exception score to liver transplant candidates when their MELD score does not adequately reflect the severity of their liver disease (I-B).