Guideline sources The following summarized guidelines for the evaluation and management of liver transplantation (LT) are prepared by our editorial team based on guidelines from the American Society of Transplantation (AST/AASLD 2013). 1 Calculator Calculator Milan criteria for liver transplant Revised King's score for liver tra Guidelines 1. Diagnostic investigations https://web.pathway.md/diseases/rec8HaI7rgrIcNPwS 1/7 6/29/23, 5:53 AM Liver transplantation Pathway Screening for osteoporosis: obtain bone mineral density (BMD) testing yearly for patients with osteopenia, and every 2 to 3 years for patients with normal BMD in the first 5 years after transplantation; thereafter, screen on the basis of progression of BMD and risk factors. B Screening for kidney disease: monitor renal function in LT recipients for the detection and management of CKD by using an estimating equation to evaluate the GFR. B Screening for malignancies: obtain an annual screening colonoscopy with biopsies in patients with PSC and IBD or other established risk factors for colorectal cancer should undergo. Consider colectomy, including continence-preserving pouch operations, when colonic biopsy reveals moderate or severe dysplasia. B Screening for colon cancer: obtain an annual colonoscopy with mucosal biopsy in patients with chronic ulcerative colitis who have undergone LT for PSC. B Evaluation of suspected infection: evaluate patients with suspected infection following LT by taking into account the intensity of immunosuppression, the timing of the presentation, the environmental and donor exposures, the recipient's history of both symptomatic and latent infections, and the utilization of prophylactic antimicrobials and immunizations. B Evaluation of suspected fungal infections: obtain blood cultures for the diagnosis of Candida bloodstream infections and Blastomyces. B Show 3 more Evaluation of suspected rejection: diagnose rejection reliably only on the basis of liver histology; take a biopsy sample before treatment initiation and classify according to the Banff criteria. B Evaluation of suspected hepatic artery thrombosis or stenosis: obtain Doppler ultrasound as first-line imaging to assess for hepatic artery thrombosis or stenosis; consider angiography to confirm the diagnosis and plan therapy. B 2. Medical management Immunosuppresive therapy: ensure that immunosuppressive drugs for LT recipients are prescribed and monitored only by physicians with knowledge and expertise in that area. The choice of agents will depend on many factors, and no one regimen can be recommended for any patient. B De-escalation of immunosuppressive therapy: withdraw corticosteroids within 6 months of transplantation for patients who receive tacrolimus as their primary immunosuppression. B Management of hypertension: aim the treatment of hypertension for a target goal of 130/80 mmHg with a combination of lifestyle modifications and pharmacological agents as appropriate. B Management of dyslipidemia: consider measuring blood lipids after a 14-hour fast annually for healthy LT recipients. An elevated LDL cholesterol level > 100 mg/dL, with or without hypertriglyceridemia, requires therapy. Introduce statin therapy if therapeutic lifestyle and dietary https://web.pathway.md/diseases/rec8HaI7rgrIcNPwS 2/7 6/29/23, 5:53 AM Liver transplantation Pathway changes are not enough. Suboptimal control with statins can be improved by the addition of ezetimibe. C Management of diabetes mellitus: aim the treatment of diabetes mellitus after LT for a HbA1c target goal of < 7.0% with a combination of lifestyle modifications and pharmacological agents as appropriate. B Management of osteoporosis: advise LT recipient with osteopenia to perform regular weight- bearing exercise and institute calcium and vitamin D supplementation. B Management of fungal infections: initiate a cautious reduction of immunosuppression to prevent immune reconstitution syndrome, especially for cryptococcal infections. B Management of tuberculosis: treat active tuberculosis by initiating a 4-drug regimen using isoniazid, rifampin, pyrazinamide, and ethambutol under the assumption of susceptible tuberculosis with adjustments in accordance with subsequent culture results. Taper to 2 drugs such as isoniazid and rifampin after 2 months, under the assumption of no resistance and continue for a minimum of 4 additional months. B Management of hepatitis C: administer antiviral therapy for significant histological disease: grade 3 inflammation and/or stage 2 fibrosis or cholestatic hepatitis. B Management of hepatitis B: administer lifelong antiviral therapy to treat patients with recurrent HBV infections. Combination antiviral therapy is superior to monotherapy when drugs with a low genetic barrier to resistance are used, whereas the discontinuation of hepatitis B immune globulin is generally reserved for patients at low risk for HBV recurrence. B Management of CMV infection (adults): treat LT recipients with CMV infection until viremia and all symptoms have resolved. B 3. Nonpharmacologic interventions Smoking cessation: advise sustained smoking cessation as the most important preventative intervention, because of the strong association of lung, head, and neck cancers with smoking. B Dietary modification: advise LT recipients not to consume water from lakes and rivers. B Show 2 more Alcohol use cessation: Encourage all patients with a prior diagnosis of ALD to remain abstinent from alcohol. B Encourage patients to enter therapy or counseling if they relapse into alcohol use. B Environmental exposures: advise LT recipients to avoid crowds to minimize exposures to respiratory illnesses during periods of maximal immunosuppression. B Show 3 more Protective habits: advise protective habits such as frequent handwashing to reduce the risk of infection with pathogens acquired by direct contact, including C. difficile, community-acquired viral infections, and pathogens found in soil. B https://web.pathway.md/diseases/rec8HaI7rgrIcNPwS 3/7 6/29/23, 5:53 AM Liver transplantation Pathway 4. Surgical interventions Management of hepatocellular carcinoma: perform resection or ablation as the treatment of choice for a solitary extrahepatic metastasis or an intrahepatic recurrence of HCC. B Bariatric surgery: consider bariatric surgery for LT recipients who become severely or morbidly obese and fail behavioral weight-loss programs, although the optimal procedure and its timing with respect to transplantation remain to be defined. C Kidney transplantation: offer kidney transplantation from deceased or living donors as the optimal therapy to improve survival for LT recipients who develop end-stage renal disease and are eligible for organ transplantation. B Retransplantation: consider retransplantation for recurrent HBV when treatment strategies to prevent or treat recurrent HBV disease are available. C Management of bilomas and biliary cast syndrome: manage bilomas and biliary cast syndrome in a center with expertise in LT medicine, radiology, and biliary endoscopy. B 5. Specific circumstances Pregnant patients (adults): advise patients to delay pregnancy for 1 year after LT and try to conceive at a time with good, stable allograft function, with maintenance immunosuppression, and with good control of any medical complications such as hypertension and diabetes. B Show 3 more Patients with primary biliary cirrhosis: Consider routine monitoring for associated autoimmune diseases (such as thyroid disease) and for osteoporosis in patients who have undergone LT for primary biliary cirrhosis. C Consider UDCA (10 to 15 mg/kg/day) in patients with histological evidence of recurrent disease, although noimpact on graft survival has been documented. C Patients with autoimmune hepatitis: consider maintaining patients on long-term, low-dose corticosteroids in addition to routine immunosuppression in patients undergoing transplantation for AIH, although there is no evidence for recommending a particular immunosuppressive regimen. C Patients with NAFLD or NASH: perform liver biopsy to confirm recurrent or de novo nonalcoholic fatty liver disease, recognize fibrosis, and exclude alternate causes of elevated liver chemistry tests. B Patients with HIV: perform frequent monitoring of calcineurin inhibitors levels in HIV-infected LT recipients receiving HAART, given the significant interactions between antiretrovirals and calcineurin inhibitors. B 6. Patient education https://web.pathway.md/diseases/rec8HaI7rgrIcNPwS 4/7 6/29/23, 5:53 AM Liver transplantation Pathway Preconception counseling: provide preconception counseling about contraception and the risks and outcomes of pregnancy in the pretransplant period to female liver transplant recipients of a child-bearing age, and reinforce after transplantation. B General counseling: educate all LT recipients about the importance of sun avoidance and sun protection through the use of a sun block with a sun protection factor of at least 15 and protective clothing. Encourage them to examine their skin on a regular basis and report any suspicious or concerning lesions to their physicians. B Hernia care counseling: counsel LT recipients with an incisional hernia on how to recognize incarcerated hernias, and advise them to seek immediate medical assistance if signs of incarceration develop. B 7. Preventative measures Routine immunizations: Provide influenza immunization to all liver transplant recipients on an annual basis. B Avoid providing live virus vaccines in all liver transplant recipients. D CMV prophylaxis: offer prophylaxis with ganciclovir or valganciclovir for a minimum of 3 months after transplantation to high-risk recipients (CMV-seronegative recipients of CMV-seropositive donor organs). B PCP prophylaxis: Administer prophylaxis against P. jirovecii with TMP-SMX for a minimum of 6 to 12 months after transplantation to all LT recipients. B Administer atovaquone or dapsone for patients who are intolerant of TMP-SMX. B HBV prophylaxis: offer long-term prophylactic therapy using a combination of antiviral agents and low-dose hepatitis B immune globulin on demand or at fixed intervals as it can effectively prevent HBV recurrence in 90% of transplant recipients. B HCV prophylaxis: avoid prophylactic antiviral therapy as part of the management of HCV disease. D 8. Follow-up and surveillance Serial laboratory testing: individualize the frequency of follow-up laboratory tests according to the time elapsed since LT, prior complications of LT, the stability of serial test results, and the underlying cause of hepatic disease. B Serial imaging: obtain MRI, CT, ERCP, and sonography, depending on the pattern of liver tests. B Monitoring of immunosuppressive therapy: review every patient's immunosuppressive regimen at least every 6 months, and adjust treatment to minimize long-term toxicities. B https://web.pathway.md/diseases/rec8HaI7rgrIcNPwS 5/7 6/29/23, 5:53 AM Liver transplantation Pathway Specialist referral: refer all LT recipients to a dermatologist after transplantation to assess cutaneous lesions, with at least an annual evaluation by a dermatologist 5 years or more after transplantation. B Follow-up liver biopsy: obtain liver histology when parenchymal injury is suspected as the cause of abnormal liver tests. B Studies 2011 Early liver transplantation for severe alcoholic hepatitis In patients with no prior episodes of alcoholic hepatitis and had scores of 0.45 according to the Lille model, undergoing early liver transplantation was superior to not undergoing liver transplantation with respect to cumulative survival at 6 months. Mathurin P et al. N Engl J Med. 2011 Nov 10. References 1. Lucey MR, Terrault N, Ojo L et al. Long-term management of the successful adult liver transplant: 2012 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Liver Transpl. 2013 Jan;19 1 3 26. Open 2. Kelly DA, Bucuvalas JC, Alonso EM et al. Long-term medical management of the pediatric patient after liver transplantation: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Liver Transpl. 2013 Aug;19 8 798 825. Open 3. Birdwell KA, Decker B, Barbarino JM et al. Clinical Pharmacogenetics Implementation Consortium CPIC Guidelines for CYP3A5 Genotype and Tacrolimus Dosing. Clin Pharmacol Ther. 2015 Jul;98 1 19 24. Open 4. Natalie M Bachir, Anne M Larson. Adult liver transplantation in the United States. Am J Med Sci. 2012 Jun;343 6 462 9. Open 5. Robert M Merion, Douglas E Schaubel, Dawn M Dykstra et al. The survival benefit of liver transplantation. Am J Transplant. 2005 Feb;5 2 307 13. Open 6. Peter T W Kim, Giuliano Testa. Living donor liver transplantation in the USA. Hepatobiliary Surg Nutr. 2016 Apr;5 2 133 40. Open 7. Paul Martin, Andrea DiMartini, Sandy Feng et al. Evaluation for liver transplantation in adults: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Hepatology. 2014 Mar;59 3 1144 65. Open 8. Anand Padmanabhan, Laura Connelly-Smith, Nicole Aqui et al. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Eighth Special Issue. J Clin Apher. 2019 Jun;34 3 171 354. Open 9. Giorgina Mieli-Vergani, Diego Vergani, Ulrich Baumann et al. Diagnosis and Management of Pediatric Autoimmune Liver Disease: ESPGHAN Hepatology Committee Position Statement. J Pediatr Gastroenterol https://web.pathway.md/diseases/rec8HaI7rgrIcNPwS 6/7 6/29/23, 5:53 AM Liver transplantation Pathway Nutr. 2018 Feb;66 2 345 360. Open 10. Tram T Tran, Joseph Ahn, Nancy S Reau. ACG Clinical Guideline: Liver Disease and Pregnancy. Am J Gastroenterol. 2016 Feb;111 2 176 94; quiz 196. Open 11. Monika Sarkar, Carla W Brady, Jaquelyn Fleckenstein et al. Reproductive Health and Liver Disease: Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021 Jan;73 1 318 365. Open 12. Jean-Marc Dumonceau, Andrea Tringali, Ioannis S Papanikolaou et al. Endoscopic biliary stenting: indications, choice of stents, and results: European Society of Gastrointestinal Endoscopy ESGE Clinical Guideline Updated October 2017. Endoscopy. 2018 Sep;50 9 910 930. Open https://web.pathway.md/diseases/rec8HaI7rgrIcNPwS 7/7