What is the purpose of ordering a Thiopurine Methyltransferase (TPMT) test in a patient with acute drug-induced liver failure?

From the Guidelines

The primary purpose of ordering a TPMT test in a patient with acute drug-induced liver failure is to identify individuals with reduced TPMT activity or complete deficiency, who are at a higher risk of developing severe toxicity from thiopurine medications, and to guide future treatment decisions. In the context of acute drug-induced liver failure, TPMT testing is crucial to determine if the liver injury was caused by thiopurine medications such as azathioprine, 6-mercaptopurine, and 6-thioguanine 1. Patients with reduced TPMT activity or complete deficiency are at significantly higher risk of developing severe toxicity from standard doses of these medications, including hepatotoxicity.

Key Points to Consider

• TPMT testing measures the activity of an enzyme that metabolizes thiopurine drugs, and patients with low TPMT activity are at increased risk of discontinuing thiopurines due to adverse effects 1.
• The test helps establish whether the patient has a genetic predisposition to thiopurine toxicity, which would explain their adverse reaction.
• If TPMT deficiency is confirmed, this information is crucial for avoiding rechallenge with the same medication and for adjusting doses if thiopurine therapy must be continued for underlying conditions like inflammatory bowel disease, autoimmune hepatitis, or after transplantation.
• The test involves a simple blood draw and can be performed even during acute illness, though interpretation may be affected by recent blood transfusions or certain medications.

Clinical Implications

• TPMT testing should be performed prior to initiation of azathioprine therapy in patients with autoimmune hepatitis, as it may help identify individuals at risk of severe toxicity 1.
• In patients with TPMT deficiency, alternative treatment options such as prednisolone monotherapy or a lower dose of prednisolone combined with mycophenolate mofetil (MMF) may be considered.
• Close monitoring of all patients started on azathioprine is mandatory, even following TPMT activity testing, as azathioprine toxicity can occur in the absence of TPMT deficiency.

From the FDA Drug Label

Consider testing in patients with severe myelosuppression or repeated episodes of myelosuppression for thiopurine S-methyltransferase (TPMT) or nucleotide diphosphatase (NUDT15) deficiency. Several published studies indicate that patients with reduced TPMT or NUDT15 activity receiving usual doses of mercaptopurine, accumulate excessive cellular concentrations of active 6-TGNs, and are at higher risk for severe myelosuppression

The purpose of ordering a Thiopurine Methyltransferase (TPMT) test in a patient with acute drug-induced liver failure is not directly stated in the context of liver failure. However, the test is relevant in the context of myelosuppression and mercaptopurine therapy.

• The test is used to identify patients with reduced TPMT activity who may be at a higher risk for severe myelosuppression when receiving mercaptopurine.
• It is not explicitly stated that the test is used to diagnose or manage acute drug-induced liver failure, but rather to guide dose adjustments of mercaptopurine in patients with severe myelosuppression or repeated episodes of myelosuppression 2, 2.

From the Research

Purpose of TPMT Test in Acute Drug-Induced Liver Failure

• The Thiopurine Methyltransferase (TPMT) test is used to assess the risk of toxicity from certain medications, such as thiopurines, which are used to treat various conditions including inflammatory bowel disease and leukemia 3, 4.
• In the context of acute drug-induced liver failure, the TPMT test may be ordered to determine if a patient has a genetic predisposition to thiopurine toxicity, which can contribute to liver injury 5, 6.
• However, the provided studies do not directly address the purpose of ordering a TPMT test in a patient with acute drug-induced liver failure.
• The studies primarily focus on the diagnosis, clinical course, and treatment of drug-induced liver injury, with no specific mention of the role of TPMT testing in this context 3, 4, 5, 6, 7.

Relevance of TPMT Test to Drug-Induced Liver Injury

• While the TPMT test is relevant to the metabolism of certain medications, its direct relevance to acute drug-induced liver failure is not clearly established in the provided studies.
• The studies suggest that drug-induced liver injury can result from a variety of medications, including antibiotics, antineoplastic agents, and traditional Chinese herb medicine 4, 6.
• The diagnosis and treatment of drug-induced liver injury typically involve the identification of the offending agent, withdrawal of the medication, and supportive care 3, 5, 7.