What labs are used to monitor liver rejection?

From the Guidelines

To monitor liver rejection, healthcare providers primarily use liver function tests (LFTs) including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and bilirubin levels, as these enzymes typically elevate during rejection episodes, with AST and ALT often rising first and most dramatically, as noted in the most recent study 1. The most critical labs for monitoring liver rejection include:

• Alanine transaminase (ALT)
• Aspartate transaminase (AST)
• Alkaline phosphatase (ALP)
• Bilirubin levels These labs are crucial because they reflect hepatocellular damage or bile flow impairment, which are indicative of liver rejection. Additionally, prothrombin time (PT) and international normalized ratio (INR) are also monitored as they reflect the liver's synthetic function, which can be affected during rejection episodes, as mentioned in 1. Complete blood counts and tacrolimus or cyclosporine blood levels are also regularly checked to ensure immunosuppression is adequate without toxicity, as discussed in 1. It's essential to note that while these labs provide valuable information, definitive diagnosis of rejection typically requires a liver biopsy, as stated in 1. Labs are usually monitored very frequently immediately post-transplant, then gradually decreased to monthly and eventually quarterly as the patient stabilizes, with any unexplained elevation in these parameters warranting immediate evaluation for possible rejection, as recommended in 1. The frequency of monitoring and the specific labs used may vary depending on the individual patient's needs and the transplant center's protocols, but the primary focus is always on preventing and detecting rejection to ensure the best possible outcomes for liver transplant patients, as emphasized in 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. Whole blood trough concentration range can be found in Table 1 Blood concentration monitoring is not a replacement for renal and liver function monitoring and tissue biopsies

The labs used to monitor liver rejection include:

• Tacrolimus blood concentrations: whole blood trough concentrations are recommended to assist in the clinical evaluation of toxicity and efficacy failure
• Renal function monitoring: to evaluate the risk of nephrotoxicity
• Liver function monitoring: to evaluate the risk of hepatic impairment
• Tissue biopsies: to directly assess liver function and rejection 2

From the Research

Liver Rejection Labs

To monitor liver rejection, several labs and tests can be utilized. These include:

• Liver biopsy, which remains the most widely used method for diagnosing allograft rejection following liver transplantation 3
• Serum enzyme monitoring, such as serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and bilirubin levels 4
• Doppler ultrasonographic (US) measurements, including portal blood velocity (PBV) and splenic pulsatility index (SPI) 5
• Quantification of dd-cfDNA and DSA, which show potential in indicating the status of allograft rejection and aiding in immunosuppression modulation 3
• mRNA microarray profiling of differentially expressed genes, as well as characterization of cytokine responses and immunophenotypic shifts following liver transplantation, which may predict and recognize rejection events 3

Lab Test Interpretation

When interpreting lab results, it is essential to consider the following:

• Hepatocellular injury is defined as disproportionate elevation of AST and ALT levels compared with alkaline phosphatase levels 4
• Cholestatic injury is defined as disproportionate elevation of alkaline phosphatase level as compared with AST and ALT levels 4
• Elevated conjugated bilirubin implies hepatocellular disease or cholestasis 4
• The degree of elevation of ALT and/or AST in the clinical setting helps guide the evaluation 4

Additional Tests

In some cases, additional tests may be necessary to evaluate liver function and diagnose rejection, such as:

• Viral hepatitis testing (A, B, and C) 4
• Assessment for nonalcoholic fatty liver disease and alcoholic liver disease 4
• Screening for hereditary hemochromatosis, autoimmune hepatitis, Wilson's disease, and alpha-1 antitrypsin deficiency 4
• Liver biopsy, which may be considered when serologic testing and imaging fail to elucidate a diagnosis, to stage a condition, or when multiple diagnoses are possible 4