From the Guidelines
Monitoring allograft function after liver transplantation requires a comprehensive approach combining laboratory tests, imaging, and clinical assessment, with regular blood tests, including liver function tests, coagulation studies, and immunosuppressant drug levels, as well as ultrasound with Doppler and liver biopsies as needed, as recommended by the most recent guidelines 1.
Key Components of Allograft Function Monitoring
- Regular blood tests, including:
- Liver function tests (ALT, AST, alkaline phosphatase, GGT, bilirubin)
- Coagulation studies (PT/INR)
- Immunosuppressant drug levels (tacrolimus, cyclosporine, or sirolimus)
- Ultrasound with Doppler to assess vascular patency and detect complications like biliary strictures
- Liver biopsies may be necessary when rejection is suspected based on abnormal liver function tests
- Clinical assessment should include monitoring for signs of infection, rejection (fever, abdominal pain, jaundice), and medication side effects
Frequency of Monitoring
- Initially, blood tests should be performed 2-3 times weekly, gradually decreasing to weekly, then monthly, and eventually every 3-6 months in stable patients
- Ultrasound with Doppler should be performed regularly, with the frequency determined by the individual patient's risk factors and clinical status
Importance of Therapeutic Drug Monitoring
- Therapeutic drug monitoring is essential to maintain immunosuppressant levels within target ranges (typically tacrolimus 5-10 ng/mL early post-transplant, decreasing to 3-8 ng/mL long-term) 1
- Adjustments to immunosuppressive regimens should be made based on individual patient needs and response to treatment, with consideration of the risk of rejection and metabolic complications
Role of Liver Biopsy
- Liver biopsy may be necessary when rejection is suspected based on abnormal liver function tests, or to investigate late allograft dysfunction, including recurrence of the original disease 1
- Histological assessment is critical in evaluating the donor liver immediately before transplantation, and may be useful in predicting fibrosis progression and identifying patients at risk of rapid fibrosis progression 1
From the FDA Drug Label
Monitoring of tacrolimus blood concentrations in conjunction with other laboratory and clinical parameters is considered an essential aid to patient management for the evaluation of rejection, toxicity, dose adjustments, and compliance. Blood concentration monitoring is not a replacement for renal and liver function monitoring and tissue biopsies Factors influencing frequency of monitoring include but are not limited to hepatic or renal dysfunction, the addition or discontinuation of potentially interacting drugs and the post-transplant time.
The methods for monitoring allograft function after liver transplantation include:
- Blood concentration monitoring of tacrolimus
- Renal function monitoring
- Liver function monitoring
- Tissue biopsies 2
From the Research
Methods for Monitoring Allograft Function
The following methods are used to monitor allograft function after liver transplantation:
- Laboratory tests, such as platelet count, transaminase and bilirubin levels, INR, factor V, lactates, and Insulin Growth Factor 1 3
- Scores, including model for end-stage liver disease, acute physiology and chronic health evaluation, sequential organ failure assessment, and model of early allograft function 3
- Indocyanine green plasma disappearance rate, which has been used as a liver function assessment technique 3
- Liver maximal function capacity test, a promising method of metabolic liver activity assessment, although its use is limited by economic cost and extrahepatic factors 3
- Liver function tests, which are routinely taken throughout the postoperative period to monitor the graft, and are inexpensive, noninvasive, and sensitive for allograft disease 4
- Evaluation of coagulation parameters and enzyme markers, which can help assess the return of newly transplanted liver function within the first days of ICU stay after liver transplantation surgery 5
- The Liver Graft Assessment Following Transplantation (L-GrAFT) risk score, which allows for a highly accurate, individualized risk estimation of 3-month graft failure following liver transplantation 6
Factors Affecting Allograft Function
Several factors can affect allograft function, including:
- Donor factors, such as graft quality and donor age 7, 6
- Recipient factors, such as pretransplant hospitalization, renal replacement therapy, mechanical ventilation, and vasopressors 6
- Procedure-related factors, such as cold ischemia times and intraoperative blood transfusions 6
- Ischemia-reperfusion injury, which is a major driver of early allograft dysfunction and primary nonfunction 7
Management of Allograft Dysfunction
The management of allograft dysfunction involves:
- Prompt identification and treatment of liver disease after transplantation 4
- Use of pharmacological interventions to improve graft function after liver transplantation 7
- Machine perfusion, which seems to be the most effective method to mitigate the negative effects of ischemia-reperfusion injury 7
- Anticoagulant therapy, which can help prevent thrombotic complications after liver transplantation 5